id sid tid token lemma pos cord-002542-f7l4ty2j 1 1 key key NN cord-002542-f7l4ty2j 1 2 : : : cord-002542-f7l4ty2j 2 1 cord-002542-f7l4ty2j cord-002542-f7l4ty2j NNP cord-002542-f7l4ty2j 3 1 authors author NNS cord-002542-f7l4ty2j 3 2 : : : cord-002542-f7l4ty2j 3 3 Jaworski Jaworski NNP cord-002542-f7l4ty2j 3 4 , , , cord-002542-f7l4ty2j 3 5 Elizabeth Elizabeth NNP cord-002542-f7l4ty2j 3 6 ; ; : cord-002542-f7l4ty2j 3 7 Routh Routh NNP cord-002542-f7l4ty2j 3 8 , , , cord-002542-f7l4ty2j 3 9 Andrew Andrew NNP cord-002542-f7l4ty2j 3 10 title title NN cord-002542-f7l4ty2j 3 11 : : : cord-002542-f7l4ty2j 4 1 Parallel parallel JJ cord-002542-f7l4ty2j 4 2 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 4 3 and and CC cord-002542-f7l4ty2j 4 4 Nanopore Nanopore NNP cord-002542-f7l4ty2j 4 5 sequencing sequencing NN cord-002542-f7l4ty2j 4 6 elucidates elucidate VBZ cord-002542-f7l4ty2j 4 7 the the DT cord-002542-f7l4ty2j 4 8 rapid rapid JJ cord-002542-f7l4ty2j 4 9 evolution evolution NN cord-002542-f7l4ty2j 4 10 of of IN cord-002542-f7l4ty2j 4 11 defective defective JJ cord-002542-f7l4ty2j 4 12 - - HYPH cord-002542-f7l4ty2j 4 13 interfering interfere VBG cord-002542-f7l4ty2j 4 14 RNAs rna NNS cord-002542-f7l4ty2j 4 15 in in IN cord-002542-f7l4ty2j 4 16 Flock Flock NNP cord-002542-f7l4ty2j 4 17 House House NNP cord-002542-f7l4ty2j 4 18 virus virus NN cord-002542-f7l4ty2j 4 19 date date NN cord-002542-f7l4ty2j 4 20 : : : cord-002542-f7l4ty2j 4 21 2017 2017 CD cord-002542-f7l4ty2j 4 22 - - HYPH cord-002542-f7l4ty2j 4 23 05 05 CD cord-002542-f7l4ty2j 4 24 - - HYPH cord-002542-f7l4ty2j 4 25 05 05 CD cord-002542-f7l4ty2j 4 26 journal journal NN cord-002542-f7l4ty2j 4 27 : : : cord-002542-f7l4ty2j 5 1 PLoS PLoS NNP cord-002542-f7l4ty2j 5 2 Pathog Pathog NNP cord-002542-f7l4ty2j 5 3 DOI DOI NNP cord-002542-f7l4ty2j 5 4 : : : cord-002542-f7l4ty2j 6 1 10.1371 10.1371 CD cord-002542-f7l4ty2j 6 2 / / SYM cord-002542-f7l4ty2j 6 3 journal.ppat.1006365 journal.ppat.1006365 NNP cord-002542-f7l4ty2j 6 4 sha sha NNP cord-002542-f7l4ty2j 6 5 : : : cord-002542-f7l4ty2j 6 6 e69a0c654041707c6ffefca96f14c2f1fe05296c e69a0c654041707c6ffefca96f14c2f1fe05296c NNP cord-002542-f7l4ty2j 6 7 doc_id doc_id CD cord-002542-f7l4ty2j 6 8 : : : cord-002542-f7l4ty2j 6 9 2542 2542 CD cord-002542-f7l4ty2j 6 10 cord_uid cord_uid NNS cord-002542-f7l4ty2j 6 11 : : : cord-002542-f7l4ty2j 7 1 f7l4ty2j f7l4ty2j RB cord-002542-f7l4ty2j 8 1 Defective defective JJ cord-002542-f7l4ty2j 8 2 - - HYPH cord-002542-f7l4ty2j 8 3 Interfering interfere VBG cord-002542-f7l4ty2j 8 4 RNAs rna NNS cord-002542-f7l4ty2j 8 5 ( ( -LRB- cord-002542-f7l4ty2j 8 6 DI DI NNP cord-002542-f7l4ty2j 8 7 - - HYPH cord-002542-f7l4ty2j 8 8 RNAs rna NNS cord-002542-f7l4ty2j 8 9 ) ) -RRB- cord-002542-f7l4ty2j 8 10 have have VBP cord-002542-f7l4ty2j 8 11 long long RB cord-002542-f7l4ty2j 8 12 been be VBN cord-002542-f7l4ty2j 8 13 known know VBN cord-002542-f7l4ty2j 8 14 to to TO cord-002542-f7l4ty2j 8 15 play play VB cord-002542-f7l4ty2j 8 16 an an DT cord-002542-f7l4ty2j 8 17 important important JJ cord-002542-f7l4ty2j 8 18 role role NN cord-002542-f7l4ty2j 8 19 in in IN cord-002542-f7l4ty2j 8 20 virus virus NN cord-002542-f7l4ty2j 8 21 replication replication NN cord-002542-f7l4ty2j 8 22 and and CC cord-002542-f7l4ty2j 8 23 transmission transmission NN cord-002542-f7l4ty2j 8 24 . . . cord-002542-f7l4ty2j 9 1 DI DI NNP cord-002542-f7l4ty2j 9 2 - - HYPH cord-002542-f7l4ty2j 9 3 RNAs rna NNS cord-002542-f7l4ty2j 9 4 emerge emerge VBP cord-002542-f7l4ty2j 9 5 during during IN cord-002542-f7l4ty2j 9 6 virus virus NN cord-002542-f7l4ty2j 9 7 passaging passaging NN cord-002542-f7l4ty2j 9 8 in in IN cord-002542-f7l4ty2j 9 9 both both DT cord-002542-f7l4ty2j 9 10 cell cell NN cord-002542-f7l4ty2j 9 11 - - HYPH cord-002542-f7l4ty2j 9 12 culture culture NN cord-002542-f7l4ty2j 9 13 and and CC cord-002542-f7l4ty2j 9 14 their -PRON- PRP$ cord-002542-f7l4ty2j 9 15 hosts host NNS cord-002542-f7l4ty2j 9 16 as as IN cord-002542-f7l4ty2j 9 17 a a DT cord-002542-f7l4ty2j 9 18 result result NN cord-002542-f7l4ty2j 9 19 of of IN cord-002542-f7l4ty2j 9 20 non non JJ cord-002542-f7l4ty2j 9 21 - - JJ cord-002542-f7l4ty2j 9 22 homologous homologous JJ cord-002542-f7l4ty2j 9 23 RNA RNA NNP cord-002542-f7l4ty2j 9 24 recombination recombination NN cord-002542-f7l4ty2j 9 25 . . . cord-002542-f7l4ty2j 10 1 However however RB cord-002542-f7l4ty2j 10 2 , , , cord-002542-f7l4ty2j 10 3 the the DT cord-002542-f7l4ty2j 10 4 principles principle NNS cord-002542-f7l4ty2j 10 5 of of IN cord-002542-f7l4ty2j 10 6 DI DI NNP cord-002542-f7l4ty2j 10 7 - - HYPH cord-002542-f7l4ty2j 10 8 RNA RNA NNP cord-002542-f7l4ty2j 10 9 emergence emergence NN cord-002542-f7l4ty2j 10 10 and and CC cord-002542-f7l4ty2j 10 11 their -PRON- PRP$ cord-002542-f7l4ty2j 10 12 subsequent subsequent JJ cord-002542-f7l4ty2j 10 13 evolution evolution NN cord-002542-f7l4ty2j 10 14 have have VBP cord-002542-f7l4ty2j 10 15 remained remain VBN cord-002542-f7l4ty2j 10 16 elusive elusive JJ cord-002542-f7l4ty2j 10 17 . . . cord-002542-f7l4ty2j 11 1 Using use VBG cord-002542-f7l4ty2j 11 2 a a DT cord-002542-f7l4ty2j 11 3 combination combination NN cord-002542-f7l4ty2j 11 4 of of IN cord-002542-f7l4ty2j 11 5 long- long- NNS cord-002542-f7l4ty2j 11 6 and and CC cord-002542-f7l4ty2j 11 7 short short RB cord-002542-f7l4ty2j 11 8 - - HYPH cord-002542-f7l4ty2j 11 9 read read VBN cord-002542-f7l4ty2j 11 10 Next Next NNP cord-002542-f7l4ty2j 11 11 - - HYPH cord-002542-f7l4ty2j 11 12 Generation Generation NNP cord-002542-f7l4ty2j 11 13 Sequencing Sequencing NNP cord-002542-f7l4ty2j 11 14 , , , cord-002542-f7l4ty2j 11 15 we -PRON- PRP cord-002542-f7l4ty2j 11 16 have have VBP cord-002542-f7l4ty2j 11 17 characterized characterize VBN cord-002542-f7l4ty2j 11 18 the the DT cord-002542-f7l4ty2j 11 19 formation formation NN cord-002542-f7l4ty2j 11 20 of of IN cord-002542-f7l4ty2j 11 21 DI DI NNP cord-002542-f7l4ty2j 11 22 - - HYPH cord-002542-f7l4ty2j 11 23 RNAs rna NNS cord-002542-f7l4ty2j 11 24 during during IN cord-002542-f7l4ty2j 11 25 serial serial JJ cord-002542-f7l4ty2j 11 26 passaging passaging NN cord-002542-f7l4ty2j 11 27 of of IN cord-002542-f7l4ty2j 11 28 Flock Flock NNP cord-002542-f7l4ty2j 11 29 House House NNP cord-002542-f7l4ty2j 11 30 virus virus NN cord-002542-f7l4ty2j 11 31 ( ( -LRB- cord-002542-f7l4ty2j 11 32 FHV FHV NNP cord-002542-f7l4ty2j 11 33 ) ) -RRB- cord-002542-f7l4ty2j 11 34 in in IN cord-002542-f7l4ty2j 11 35 cell cell NN cord-002542-f7l4ty2j 11 36 - - HYPH cord-002542-f7l4ty2j 11 37 culture culture NN cord-002542-f7l4ty2j 11 38 over over IN cord-002542-f7l4ty2j 11 39 a a DT cord-002542-f7l4ty2j 11 40 period period NN cord-002542-f7l4ty2j 11 41 of of IN cord-002542-f7l4ty2j 11 42 30 30 CD cord-002542-f7l4ty2j 11 43 days day NNS cord-002542-f7l4ty2j 11 44 in in IN cord-002542-f7l4ty2j 11 45 order order NN cord-002542-f7l4ty2j 11 46 to to TO cord-002542-f7l4ty2j 11 47 elucidate elucidate VB cord-002542-f7l4ty2j 11 48 the the DT cord-002542-f7l4ty2j 11 49 pathways pathway NNS cord-002542-f7l4ty2j 11 50 and and CC cord-002542-f7l4ty2j 11 51 potential potential JJ cord-002542-f7l4ty2j 11 52 mechanisms mechanism NNS cord-002542-f7l4ty2j 11 53 of of IN cord-002542-f7l4ty2j 11 54 DI DI NNP cord-002542-f7l4ty2j 11 55 - - HYPH cord-002542-f7l4ty2j 11 56 RNA RNA NNP cord-002542-f7l4ty2j 11 57 emergence emergence NN cord-002542-f7l4ty2j 11 58 and and CC cord-002542-f7l4ty2j 11 59 evolution evolution NN cord-002542-f7l4ty2j 11 60 . . . cord-002542-f7l4ty2j 12 1 For for IN cord-002542-f7l4ty2j 12 2 short short RB cord-002542-f7l4ty2j 12 3 - - HYPH cord-002542-f7l4ty2j 12 4 read read NN cord-002542-f7l4ty2j 12 5 RNAseq RNAseq NNP cord-002542-f7l4ty2j 12 6 , , , cord-002542-f7l4ty2j 12 7 we -PRON- PRP cord-002542-f7l4ty2j 12 8 employed employ VBD cord-002542-f7l4ty2j 12 9 ‘ ' `` cord-002542-f7l4ty2j 12 10 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 12 11 ’ ' '' cord-002542-f7l4ty2j 12 12 due due IN cord-002542-f7l4ty2j 12 13 to to IN cord-002542-f7l4ty2j 12 14 its -PRON- PRP$ cord-002542-f7l4ty2j 12 15 ability ability NN cord-002542-f7l4ty2j 12 16 to to TO cord-002542-f7l4ty2j 12 17 sensitively sensitively RB cord-002542-f7l4ty2j 12 18 and and CC cord-002542-f7l4ty2j 12 19 confidently confidently RB cord-002542-f7l4ty2j 12 20 detect detect VB cord-002542-f7l4ty2j 12 21 RNA RNA NNP cord-002542-f7l4ty2j 12 22 recombination recombination NN cord-002542-f7l4ty2j 12 23 events event NNS cord-002542-f7l4ty2j 12 24 with with IN cord-002542-f7l4ty2j 12 25 nucleotide nucleotide JJ cord-002542-f7l4ty2j 12 26 resolution resolution NN cord-002542-f7l4ty2j 12 27 . . . cord-002542-f7l4ty2j 13 1 In in IN cord-002542-f7l4ty2j 13 2 parallel parallel NN cord-002542-f7l4ty2j 13 3 , , , cord-002542-f7l4ty2j 13 4 we -PRON- PRP cord-002542-f7l4ty2j 13 5 used use VBD cord-002542-f7l4ty2j 13 6 the the DT cord-002542-f7l4ty2j 13 7 Oxford Oxford NNP cord-002542-f7l4ty2j 13 8 Nanopore Nanopore NNP cord-002542-f7l4ty2j 13 9 Technologies Technologies NNP cord-002542-f7l4ty2j 13 10 ’s ’s POS cord-002542-f7l4ty2j 13 11 ( ( -LRB- cord-002542-f7l4ty2j 13 12 ONT ONT NNP cord-002542-f7l4ty2j 13 13 ) ) -RRB- cord-002542-f7l4ty2j 13 14 MinION MinION NNS cord-002542-f7l4ty2j 13 15 to to TO cord-002542-f7l4ty2j 13 16 resolve resolve VB cord-002542-f7l4ty2j 13 17 full full JJ cord-002542-f7l4ty2j 13 18 - - HYPH cord-002542-f7l4ty2j 13 19 length length NN cord-002542-f7l4ty2j 13 20 defective defective JJ cord-002542-f7l4ty2j 13 21 and and CC cord-002542-f7l4ty2j 13 22 wild wild JJ cord-002542-f7l4ty2j 13 23 - - HYPH cord-002542-f7l4ty2j 13 24 type type NN cord-002542-f7l4ty2j 13 25 viral viral JJ cord-002542-f7l4ty2j 13 26 genomes genome NNS cord-002542-f7l4ty2j 13 27 . . . cord-002542-f7l4ty2j 14 1 Together together RB cord-002542-f7l4ty2j 14 2 , , , cord-002542-f7l4ty2j 14 3 these these DT cord-002542-f7l4ty2j 14 4 accurately accurately RB cord-002542-f7l4ty2j 14 5 resolve resolve VBP cord-002542-f7l4ty2j 14 6 both both CC cord-002542-f7l4ty2j 14 7 rare rare JJ cord-002542-f7l4ty2j 14 8 and and CC cord-002542-f7l4ty2j 14 9 common common JJ cord-002542-f7l4ty2j 14 10 RNA RNA NNP cord-002542-f7l4ty2j 14 11 recombination recombination NN cord-002542-f7l4ty2j 14 12 events event NNS cord-002542-f7l4ty2j 14 13 , , , cord-002542-f7l4ty2j 14 14 determine determine VB cord-002542-f7l4ty2j 14 15 the the DT cord-002542-f7l4ty2j 14 16 correlation correlation NN cord-002542-f7l4ty2j 14 17 between between IN cord-002542-f7l4ty2j 14 18 recombination recombination NN cord-002542-f7l4ty2j 14 19 events event NNS cord-002542-f7l4ty2j 14 20 , , , cord-002542-f7l4ty2j 14 21 and and CC cord-002542-f7l4ty2j 14 22 quantifies quantify VBZ cord-002542-f7l4ty2j 14 23 the the DT cord-002542-f7l4ty2j 14 24 relative relative JJ cord-002542-f7l4ty2j 14 25 abundance abundance NN cord-002542-f7l4ty2j 14 26 of of IN cord-002542-f7l4ty2j 14 27 different different JJ cord-002542-f7l4ty2j 14 28 DI DI NNP cord-002542-f7l4ty2j 14 29 - - HYPH cord-002542-f7l4ty2j 14 30 RNAs rna NNS cord-002542-f7l4ty2j 14 31 throughout throughout IN cord-002542-f7l4ty2j 14 32 passaging passage VBG cord-002542-f7l4ty2j 14 33 . . . cord-002542-f7l4ty2j 15 1 We -PRON- PRP cord-002542-f7l4ty2j 15 2 observe observe VBP cord-002542-f7l4ty2j 15 3 the the DT cord-002542-f7l4ty2j 15 4 formation formation NN cord-002542-f7l4ty2j 15 5 of of IN cord-002542-f7l4ty2j 15 6 a a DT cord-002542-f7l4ty2j 15 7 diverse diverse JJ cord-002542-f7l4ty2j 15 8 pool pool NN cord-002542-f7l4ty2j 15 9 of of IN cord-002542-f7l4ty2j 15 10 defective defective JJ cord-002542-f7l4ty2j 15 11 RNAs rna NNS cord-002542-f7l4ty2j 15 12 at at IN cord-002542-f7l4ty2j 15 13 each each DT cord-002542-f7l4ty2j 15 14 stage stage NN cord-002542-f7l4ty2j 15 15 of of IN cord-002542-f7l4ty2j 15 16 viral viral JJ cord-002542-f7l4ty2j 15 17 passaging passaging NN cord-002542-f7l4ty2j 15 18 . . . cord-002542-f7l4ty2j 16 1 However however RB cord-002542-f7l4ty2j 16 2 , , , cord-002542-f7l4ty2j 16 3 many many JJ cord-002542-f7l4ty2j 16 4 of of IN cord-002542-f7l4ty2j 16 5 these these DT cord-002542-f7l4ty2j 16 6 ‘ ' `` cord-002542-f7l4ty2j 16 7 intermediate intermediate JJ cord-002542-f7l4ty2j 16 8 ’ ' '' cord-002542-f7l4ty2j 16 9 species specie NNS cord-002542-f7l4ty2j 16 10 , , , cord-002542-f7l4ty2j 16 11 while while IN cord-002542-f7l4ty2j 16 12 present present JJ cord-002542-f7l4ty2j 16 13 in in IN cord-002542-f7l4ty2j 16 14 early early JJ cord-002542-f7l4ty2j 16 15 stages stage NNS cord-002542-f7l4ty2j 16 16 of of IN cord-002542-f7l4ty2j 16 17 passaging passaging NN cord-002542-f7l4ty2j 16 18 , , , cord-002542-f7l4ty2j 16 19 do do VBP cord-002542-f7l4ty2j 16 20 not not RB cord-002542-f7l4ty2j 16 21 accumulate accumulate VB cord-002542-f7l4ty2j 16 22 . . . cord-002542-f7l4ty2j 17 1 After after IN cord-002542-f7l4ty2j 17 2 approximately approximately RB cord-002542-f7l4ty2j 17 3 9 9 CD cord-002542-f7l4ty2j 17 4 days day NNS cord-002542-f7l4ty2j 17 5 of of IN cord-002542-f7l4ty2j 17 6 passaging passaging NN cord-002542-f7l4ty2j 17 7 we -PRON- PRP cord-002542-f7l4ty2j 17 8 observe observe VBP cord-002542-f7l4ty2j 17 9 the the DT cord-002542-f7l4ty2j 17 10 rapid rapid JJ cord-002542-f7l4ty2j 17 11 accumulation accumulation NN cord-002542-f7l4ty2j 17 12 of of IN cord-002542-f7l4ty2j 17 13 DI DI NNP cord-002542-f7l4ty2j 17 14 - - HYPH cord-002542-f7l4ty2j 17 15 RNAs rna NNS cord-002542-f7l4ty2j 17 16 with with IN cord-002542-f7l4ty2j 17 17 a a DT cord-002542-f7l4ty2j 17 18 correlated correlate VBN cord-002542-f7l4ty2j 17 19 reduction reduction NN cord-002542-f7l4ty2j 17 20 in in IN cord-002542-f7l4ty2j 17 21 specific specific JJ cord-002542-f7l4ty2j 17 22 infectivity infectivity NN cord-002542-f7l4ty2j 17 23 and and CC cord-002542-f7l4ty2j 17 24 with with IN cord-002542-f7l4ty2j 17 25 the the DT cord-002542-f7l4ty2j 17 26 Nanopore Nanopore NNP cord-002542-f7l4ty2j 17 27 data datum NNS cord-002542-f7l4ty2j 18 1 find find VB cord-002542-f7l4ty2j 18 2 that that IN cord-002542-f7l4ty2j 18 3 DI DI NNP cord-002542-f7l4ty2j 18 4 - - HYPH cord-002542-f7l4ty2j 18 5 RNAs rna NNS cord-002542-f7l4ty2j 18 6 are be VBP cord-002542-f7l4ty2j 18 7 characterized characterize VBN cord-002542-f7l4ty2j 18 8 by by IN cord-002542-f7l4ty2j 18 9 multiple multiple JJ cord-002542-f7l4ty2j 18 10 RNA RNA NNP cord-002542-f7l4ty2j 18 11 recombination recombination NN cord-002542-f7l4ty2j 18 12 events event NNS cord-002542-f7l4ty2j 18 13 . . . cord-002542-f7l4ty2j 19 1 This this DT cord-002542-f7l4ty2j 19 2 suggests suggest VBZ cord-002542-f7l4ty2j 19 3 that that IN cord-002542-f7l4ty2j 19 4 intermediate intermediate JJ cord-002542-f7l4ty2j 19 5 DI DI NNP cord-002542-f7l4ty2j 19 6 - - HYPH cord-002542-f7l4ty2j 19 7 RNA RNA NNP cord-002542-f7l4ty2j 19 8 species specie NNS cord-002542-f7l4ty2j 19 9 are be VBP cord-002542-f7l4ty2j 19 10 not not RB cord-002542-f7l4ty2j 19 11 competitive competitive JJ cord-002542-f7l4ty2j 19 12 and and CC cord-002542-f7l4ty2j 19 13 that that IN cord-002542-f7l4ty2j 19 14 multiple multiple JJ cord-002542-f7l4ty2j 19 15 recombination recombination NN cord-002542-f7l4ty2j 19 16 events event NNS cord-002542-f7l4ty2j 19 17 interact interact VBP cord-002542-f7l4ty2j 19 18 epistatically epistatically RB cord-002542-f7l4ty2j 19 19 to to TO cord-002542-f7l4ty2j 19 20 confer confer VB cord-002542-f7l4ty2j 19 21 ‘ ' `` cord-002542-f7l4ty2j 19 22 mature mature JJ cord-002542-f7l4ty2j 19 23 ’ ' '' cord-002542-f7l4ty2j 19 24 DI di NN cord-002542-f7l4ty2j 19 25 - - HYPH cord-002542-f7l4ty2j 19 26 RNAs rna NNS cord-002542-f7l4ty2j 19 27 with with IN cord-002542-f7l4ty2j 19 28 their -PRON- PRP$ cord-002542-f7l4ty2j 19 29 selective selective JJ cord-002542-f7l4ty2j 19 30 advantage advantage NN cord-002542-f7l4ty2j 19 31 allowing allow VBG cord-002542-f7l4ty2j 19 32 for for IN cord-002542-f7l4ty2j 19 33 their -PRON- PRP$ cord-002542-f7l4ty2j 19 34 rapid rapid JJ cord-002542-f7l4ty2j 19 35 accumulation accumulation NN cord-002542-f7l4ty2j 19 36 . . . cord-002542-f7l4ty2j 20 1 Alternatively alternatively RB cord-002542-f7l4ty2j 20 2 , , , cord-002542-f7l4ty2j 20 3 it -PRON- PRP cord-002542-f7l4ty2j 20 4 is be VBZ cord-002542-f7l4ty2j 20 5 possible possible JJ cord-002542-f7l4ty2j 20 6 that that IN cord-002542-f7l4ty2j 20 7 mature mature JJ cord-002542-f7l4ty2j 20 8 DI DI NNP cord-002542-f7l4ty2j 20 9 - - HYPH cord-002542-f7l4ty2j 20 10 RNA RNA NNP cord-002542-f7l4ty2j 20 11 species specie NNS cord-002542-f7l4ty2j 20 12 are be VBP cord-002542-f7l4ty2j 20 13 generated generate VBN cord-002542-f7l4ty2j 20 14 in in IN cord-002542-f7l4ty2j 20 15 a a DT cord-002542-f7l4ty2j 20 16 single single JJ cord-002542-f7l4ty2j 20 17 event event NN cord-002542-f7l4ty2j 20 18 involving involve VBG cord-002542-f7l4ty2j 20 19 multiple multiple JJ cord-002542-f7l4ty2j 20 20 RNA RNA NNP cord-002542-f7l4ty2j 20 21 rearrangements rearrangement NNS cord-002542-f7l4ty2j 20 22 . . . cord-002542-f7l4ty2j 21 1 These these DT cord-002542-f7l4ty2j 21 2 insights insight NNS cord-002542-f7l4ty2j 21 3 have have VBP cord-002542-f7l4ty2j 21 4 important important JJ cord-002542-f7l4ty2j 21 5 consequences consequence NNS cord-002542-f7l4ty2j 21 6 for for IN cord-002542-f7l4ty2j 21 7 our -PRON- PRP$ cord-002542-f7l4ty2j 21 8 understanding understanding NN cord-002542-f7l4ty2j 21 9 of of IN cord-002542-f7l4ty2j 21 10 the the DT cord-002542-f7l4ty2j 21 11 mechanisms mechanism NNS cord-002542-f7l4ty2j 21 12 , , , cord-002542-f7l4ty2j 21 13 determinants determinant NNS cord-002542-f7l4ty2j 21 14 and and CC cord-002542-f7l4ty2j 21 15 limitations limitation NNS cord-002542-f7l4ty2j 21 16 in in IN cord-002542-f7l4ty2j 21 17 the the DT cord-002542-f7l4ty2j 21 18 emergence emergence NN cord-002542-f7l4ty2j 21 19 and and CC cord-002542-f7l4ty2j 21 20 evolution evolution NN cord-002542-f7l4ty2j 21 21 of of IN cord-002542-f7l4ty2j 21 22 DI DI NNP cord-002542-f7l4ty2j 21 23 - - HYPH cord-002542-f7l4ty2j 21 24 RNAs rna NNS cord-002542-f7l4ty2j 21 25 . . . cord-002542-f7l4ty2j 22 1 Introduction Introduction NNP cord-002542-f7l4ty2j 22 2 RNA RNA NNP cord-002542-f7l4ty2j 22 3 viruses virus NNS cord-002542-f7l4ty2j 22 4 are be VBP cord-002542-f7l4ty2j 22 5 extremely extremely RB cord-002542-f7l4ty2j 22 6 diverse diverse JJ cord-002542-f7l4ty2j 22 7 and and CC cord-002542-f7l4ty2j 22 8 rapidly rapidly RB cord-002542-f7l4ty2j 22 9 evolving evolve VBG cord-002542-f7l4ty2j 22 10 . . . cord-002542-f7l4ty2j 23 1 Their -PRON- PRP$ cord-002542-f7l4ty2j 23 2 RNA RNA NNP cord-002542-f7l4ty2j 23 3 - - HYPH cord-002542-f7l4ty2j 23 4 dependent dependent JJ cord-002542-f7l4ty2j 23 5 RNA RNA NNP cord-002542-f7l4ty2j 23 6 polymerases polymerase NNS cord-002542-f7l4ty2j 23 7 ( ( -LRB- cord-002542-f7l4ty2j 23 8 RdRps RdRps NNP cord-002542-f7l4ty2j 23 9 ) ) -RRB- cord-002542-f7l4ty2j 23 10 readily readily RB cord-002542-f7l4ty2j 23 11 generate generate VBP cord-002542-f7l4ty2j 23 12 single single JJ cord-002542-f7l4ty2j 23 13 - - HYPH cord-002542-f7l4ty2j 23 14 nucleotide nucleotide NN cord-002542-f7l4ty2j 23 15 variants variant NNS cord-002542-f7l4ty2j 23 16 whilst whilst IN cord-002542-f7l4ty2j 23 17 lacking lack VBG cord-002542-f7l4ty2j 23 18 proof proof NN cord-002542-f7l4ty2j 23 19 - - HYPH cord-002542-f7l4ty2j 23 20 reading reading NN cord-002542-f7l4ty2j 23 21 capabilities capability NNS cord-002542-f7l4ty2j 23 22 [ [ -LRB- cord-002542-f7l4ty2j 23 23 1 1 CD cord-002542-f7l4ty2j 23 24 ] ] -RRB- cord-002542-f7l4ty2j 23 25 . . . cord-002542-f7l4ty2j 24 1 RdRps RdRps NNP cord-002542-f7l4ty2j 24 2 are be VBP cord-002542-f7l4ty2j 24 3 also also RB cord-002542-f7l4ty2j 24 4 highly highly RB cord-002542-f7l4ty2j 24 5 prone prone JJ cord-002542-f7l4ty2j 24 6 to to IN cord-002542-f7l4ty2j 24 7 RNA rna NN cord-002542-f7l4ty2j 24 8 recombination recombination NN cord-002542-f7l4ty2j 24 9 [ [ -LRB- cord-002542-f7l4ty2j 24 10 2 2 CD cord-002542-f7l4ty2j 24 11 ] ] -RRB- cord-002542-f7l4ty2j 24 12 ; ; : cord-002542-f7l4ty2j 24 13 either either CC cord-002542-f7l4ty2j 24 14 through through IN cord-002542-f7l4ty2j 24 15 template template NN cord-002542-f7l4ty2j 24 16 - - HYPH cord-002542-f7l4ty2j 24 17 switching switch VBG cord-002542-f7l4ty2j 24 18 [ [ -LRB- cord-002542-f7l4ty2j 24 19 3 3 CD cord-002542-f7l4ty2j 24 20 ] ] -RRB- cord-002542-f7l4ty2j 24 21 or or CC cord-002542-f7l4ty2j 24 22 through through IN cord-002542-f7l4ty2j 24 23 non non JJ cord-002542-f7l4ty2j 24 24 - - JJ cord-002542-f7l4ty2j 24 25 replicative replicative JJ cord-002542-f7l4ty2j 24 26 end end NN cord-002542-f7l4ty2j 24 27 - - HYPH cord-002542-f7l4ty2j 24 28 joining join VBG cord-002542-f7l4ty2j 24 29 [ [ -LRB- cord-002542-f7l4ty2j 24 30 4 4 CD cord-002542-f7l4ty2j 24 31 ] ] -RRB- cord-002542-f7l4ty2j 24 32 . . . cord-002542-f7l4ty2j 25 1 RNA RNA NNP cord-002542-f7l4ty2j 25 2 recombination recombination NN cord-002542-f7l4ty2j 25 3 has have VBZ cord-002542-f7l4ty2j 25 4 been be VBN cord-002542-f7l4ty2j 25 5 demonstrated demonstrate VBN cord-002542-f7l4ty2j 25 6 to to TO cord-002542-f7l4ty2j 25 7 be be VB cord-002542-f7l4ty2j 25 8 responsible responsible JJ cord-002542-f7l4ty2j 25 9 for for IN cord-002542-f7l4ty2j 25 10 the the DT cord-002542-f7l4ty2j 25 11 emergence emergence NN cord-002542-f7l4ty2j 25 12 of of IN cord-002542-f7l4ty2j 25 13 new new JJ cord-002542-f7l4ty2j 25 14 strains strain NNS cord-002542-f7l4ty2j 25 15 or or CC cord-002542-f7l4ty2j 25 16 species specie NNS cord-002542-f7l4ty2j 25 17 of of IN cord-002542-f7l4ty2j 25 18 viruses virus NNS cord-002542-f7l4ty2j 25 19 such such JJ cord-002542-f7l4ty2j 25 20 as as IN cord-002542-f7l4ty2j 25 21 rhinoviruses rhinovirus NNS cord-002542-f7l4ty2j 25 22 [ [ -LRB- cord-002542-f7l4ty2j 25 23 5 5 CD cord-002542-f7l4ty2j 25 24 ] ] -RRB- cord-002542-f7l4ty2j 25 25 and and CC cord-002542-f7l4ty2j 25 26 dengue dengue NN cord-002542-f7l4ty2j 25 27 virus virus NN cord-002542-f7l4ty2j 25 28 [ [ -LRB- cord-002542-f7l4ty2j 25 29 6 6 CD cord-002542-f7l4ty2j 25 30 ] ] -RRB- cord-002542-f7l4ty2j 25 31 , , , cord-002542-f7l4ty2j 25 32 and and CC cord-002542-f7l4ty2j 25 33 the the DT cord-002542-f7l4ty2j 25 34 formation formation NN cord-002542-f7l4ty2j 25 35 of of IN cord-002542-f7l4ty2j 25 36 vaccine vaccine NN cord-002542-f7l4ty2j 25 37 - - HYPH cord-002542-f7l4ty2j 25 38 derived derive VBN cord-002542-f7l4ty2j 25 39 poliovirus poliovirus NN cord-002542-f7l4ty2j 25 40 [ [ -LRB- cord-002542-f7l4ty2j 25 41 7 7 CD cord-002542-f7l4ty2j 25 42 ] ] -RRB- cord-002542-f7l4ty2j 25 43 . . . cord-002542-f7l4ty2j 26 1 Non non JJ cord-002542-f7l4ty2j 26 2 - - JJ cord-002542-f7l4ty2j 26 3 homologous homologous JJ cord-002542-f7l4ty2j 26 4 RNA RNA NNP cord-002542-f7l4ty2j 26 5 recombination recombination NN cord-002542-f7l4ty2j 26 6 is be VBZ cord-002542-f7l4ty2j 26 7 also also RB cord-002542-f7l4ty2j 26 8 responsible responsible JJ cord-002542-f7l4ty2j 26 9 for for IN cord-002542-f7l4ty2j 26 10 the the DT cord-002542-f7l4ty2j 26 11 generation generation NN cord-002542-f7l4ty2j 26 12 of of IN cord-002542-f7l4ty2j 26 13 defective defective JJ cord-002542-f7l4ty2j 26 14 RNAs rna NNS cord-002542-f7l4ty2j 26 15 [ [ -LRB- cord-002542-f7l4ty2j 26 16 8 8 CD cord-002542-f7l4ty2j 26 17 , , , cord-002542-f7l4ty2j 26 18 9 9 CD cord-002542-f7l4ty2j 26 19 ] ] -RRB- cord-002542-f7l4ty2j 26 20 . . . cord-002542-f7l4ty2j 27 1 These these DT cord-002542-f7l4ty2j 27 2 are be VBP cord-002542-f7l4ty2j 27 3 versions version NNS cord-002542-f7l4ty2j 27 4 of of IN cord-002542-f7l4ty2j 27 5 the the DT cord-002542-f7l4ty2j 27 6 parental parental JJ cord-002542-f7l4ty2j 27 7 viral viral JJ cord-002542-f7l4ty2j 27 8 genome genome NN cord-002542-f7l4ty2j 27 9 that that WDT cord-002542-f7l4ty2j 27 10 can can MD cord-002542-f7l4ty2j 27 11 arise arise VB cord-002542-f7l4ty2j 27 12 naturally naturally RB cord-002542-f7l4ty2j 27 13 during during IN cord-002542-f7l4ty2j 27 14 the the DT cord-002542-f7l4ty2j 27 15 course course NN cord-002542-f7l4ty2j 27 16 of of IN cord-002542-f7l4ty2j 27 17 viral viral JJ cord-002542-f7l4ty2j 27 18 passaging passaging NN cord-002542-f7l4ty2j 27 19 but but CC cord-002542-f7l4ty2j 27 20 have have VBP cord-002542-f7l4ty2j 27 21 been be VBN cord-002542-f7l4ty2j 27 22 truncated truncate VBN cord-002542-f7l4ty2j 27 23 and and CC cord-002542-f7l4ty2j 27 24 rearranged rearrange VBN cord-002542-f7l4ty2j 27 25 by by IN cord-002542-f7l4ty2j 27 26 RNA RNA NNP cord-002542-f7l4ty2j 27 27 recombination recombination NN cord-002542-f7l4ty2j 27 28 . . . cord-002542-f7l4ty2j 28 1 While while IN cord-002542-f7l4ty2j 28 2 not not RB cord-002542-f7l4ty2j 28 3 encoding encode VBG cord-002542-f7l4ty2j 28 4 for for IN cord-002542-f7l4ty2j 28 5 functional functional JJ cord-002542-f7l4ty2j 28 6 viruses virus NNS cord-002542-f7l4ty2j 28 7 themselves -PRON- PRP cord-002542-f7l4ty2j 28 8 , , , cord-002542-f7l4ty2j 28 9 they -PRON- PRP cord-002542-f7l4ty2j 28 10 can can MD cord-002542-f7l4ty2j 28 11 be be VB cord-002542-f7l4ty2j 28 12 amplified amplify VBN cord-002542-f7l4ty2j 28 13 and and CC cord-002542-f7l4ty2j 28 14 co co JJ cord-002542-f7l4ty2j 28 15 - - JJ cord-002542-f7l4ty2j 28 16 passaged passaged JJ cord-002542-f7l4ty2j 28 17 with with IN cord-002542-f7l4ty2j 28 18 the the DT cord-002542-f7l4ty2j 28 19 help help NN cord-002542-f7l4ty2j 28 20 of of IN cord-002542-f7l4ty2j 28 21 the the DT cord-002542-f7l4ty2j 28 22 wild wild JJ cord-002542-f7l4ty2j 28 23 - - HYPH cord-002542-f7l4ty2j 28 24 type type NN cord-002542-f7l4ty2j 28 25 ' ' `` cord-002542-f7l4ty2j 28 26 helper helper NN cord-002542-f7l4ty2j 28 27 ' ' '' cord-002542-f7l4ty2j 28 28 virus virus NN cord-002542-f7l4ty2j 28 29 that that WDT cord-002542-f7l4ty2j 28 30 provides provide VBZ cord-002542-f7l4ty2j 28 31 the the DT cord-002542-f7l4ty2j 28 32 necessary necessary JJ cord-002542-f7l4ty2j 28 33 machinery machinery NN cord-002542-f7l4ty2j 28 34 for for IN cord-002542-f7l4ty2j 28 35 replication replication NN cord-002542-f7l4ty2j 28 36 , , , cord-002542-f7l4ty2j 28 37 encapsidation encapsidation NN cord-002542-f7l4ty2j 28 38 and and CC cord-002542-f7l4ty2j 28 39 transmission transmission NN cord-002542-f7l4ty2j 28 40 . . . cord-002542-f7l4ty2j 29 1 A a DT cord-002542-f7l4ty2j 29 2 defective defective JJ cord-002542-f7l4ty2j 29 3 RNA RNA NNP cord-002542-f7l4ty2j 29 4 that that WDT cord-002542-f7l4ty2j 29 5 accumulates accumulate VBZ cord-002542-f7l4ty2j 29 6 to to IN cord-002542-f7l4ty2j 29 7 such such PDT cord-002542-f7l4ty2j 29 8 an an DT cord-002542-f7l4ty2j 29 9 extent extent NN cord-002542-f7l4ty2j 29 10 as as IN cord-002542-f7l4ty2j 29 11 to to TO cord-002542-f7l4ty2j 29 12 compete compete VB cord-002542-f7l4ty2j 29 13 with with IN cord-002542-f7l4ty2j 29 14 or or CC cord-002542-f7l4ty2j 29 15 otherwise otherwise RB cord-002542-f7l4ty2j 29 16 attenuate attenuate VB cord-002542-f7l4ty2j 29 17 the the DT cord-002542-f7l4ty2j 29 18 replication replication NN cord-002542-f7l4ty2j 29 19 of of IN cord-002542-f7l4ty2j 29 20 the the DT cord-002542-f7l4ty2j 29 21 parental parental JJ cord-002542-f7l4ty2j 29 22 virus virus NN cord-002542-f7l4ty2j 29 23 is be VBZ cord-002542-f7l4ty2j 29 24 known know VBN cord-002542-f7l4ty2j 29 25 as as IN cord-002542-f7l4ty2j 29 26 a a DT cord-002542-f7l4ty2j 29 27 Defective Defective NNP cord-002542-f7l4ty2j 29 28 - - HYPH cord-002542-f7l4ty2j 29 29 Interfering interfere VBG cord-002542-f7l4ty2j 29 30 RNA RNA NNP cord-002542-f7l4ty2j 29 31 ( ( -LRB- cord-002542-f7l4ty2j 29 32 DI DI NNP cord-002542-f7l4ty2j 29 33 - - HYPH cord-002542-f7l4ty2j 29 34 RNA RNA NNP cord-002542-f7l4ty2j 29 35 ) ) -RRB- cord-002542-f7l4ty2j 29 36 [ [ -LRB- cord-002542-f7l4ty2j 29 37 10 10 CD cord-002542-f7l4ty2j 29 38 ] ] -RRB- cord-002542-f7l4ty2j 29 39 . . . cord-002542-f7l4ty2j 30 1 DI DI NNP cord-002542-f7l4ty2j 30 2 - - HYPH cord-002542-f7l4ty2j 30 3 RNAs rna NNS cord-002542-f7l4ty2j 30 4 can can MD cord-002542-f7l4ty2j 30 5 attenuate attenuate VB cord-002542-f7l4ty2j 30 6 the the DT cord-002542-f7l4ty2j 30 7 viral viral JJ cord-002542-f7l4ty2j 30 8 infection infection NN cord-002542-f7l4ty2j 30 9 via via IN cord-002542-f7l4ty2j 30 10 a a DT cord-002542-f7l4ty2j 30 11 variety variety NN cord-002542-f7l4ty2j 30 12 of of IN cord-002542-f7l4ty2j 30 13 proposed propose VBN cord-002542-f7l4ty2j 30 14 mechanisms mechanism NNS cord-002542-f7l4ty2j 30 15 such such JJ cord-002542-f7l4ty2j 30 16 as as IN cord-002542-f7l4ty2j 30 17 the the DT cord-002542-f7l4ty2j 30 18 saturation saturation NN cord-002542-f7l4ty2j 30 19 of of IN cord-002542-f7l4ty2j 30 20 the the DT cord-002542-f7l4ty2j 30 21 viral viral JJ cord-002542-f7l4ty2j 30 22 replicative replicative JJ cord-002542-f7l4ty2j 30 23 machinery machinery NN cord-002542-f7l4ty2j 30 24 , , , cord-002542-f7l4ty2j 30 25 sequestration sequestration NN cord-002542-f7l4ty2j 30 26 of of IN cord-002542-f7l4ty2j 30 27 essential essential JJ cord-002542-f7l4ty2j 30 28 cellular cellular JJ cord-002542-f7l4ty2j 30 29 cofactors cofactor NNS cord-002542-f7l4ty2j 30 30 , , , cord-002542-f7l4ty2j 30 31 and/ and/ CD cord-002542-f7l4ty2j 30 32 or or CC cord-002542-f7l4ty2j 30 33 induction induction NN cord-002542-f7l4ty2j 30 34 of of IN cord-002542-f7l4ty2j 30 35 innate innate JJ cord-002542-f7l4ty2j 30 36 immune immune JJ cord-002542-f7l4ty2j 30 37 responses response NNS cord-002542-f7l4ty2j 30 38 [ [ -LRB- cord-002542-f7l4ty2j 30 39 10 10 CD cord-002542-f7l4ty2j 30 40 ] ] -RRB- cord-002542-f7l4ty2j 30 41 [ [ -LRB- cord-002542-f7l4ty2j 30 42 11 11 CD cord-002542-f7l4ty2j 30 43 ] ] -RRB- cord-002542-f7l4ty2j 30 44 [ [ -LRB- cord-002542-f7l4ty2j 30 45 12 12 CD cord-002542-f7l4ty2j 30 46 ] ] -RRB- cord-002542-f7l4ty2j 30 47 [ [ -LRB- cord-002542-f7l4ty2j 30 48 13 13 CD cord-002542-f7l4ty2j 30 49 ] ] -RRB- cord-002542-f7l4ty2j 30 50 [ [ -LRB- cord-002542-f7l4ty2j 30 51 14 14 CD cord-002542-f7l4ty2j 30 52 ] ] -RRB- cord-002542-f7l4ty2j 30 53 . . . cord-002542-f7l4ty2j 31 1 DI DI NNP cord-002542-f7l4ty2j 31 2 - - HYPH cord-002542-f7l4ty2j 31 3 RNAs rna NNS cord-002542-f7l4ty2j 31 4 have have VBP cord-002542-f7l4ty2j 31 5 been be VBN cord-002542-f7l4ty2j 31 6 well well RB cord-002542-f7l4ty2j 31 7 characterized characterize VBN cord-002542-f7l4ty2j 31 8 for for IN cord-002542-f7l4ty2j 31 9 a a DT cord-002542-f7l4ty2j 31 10 number number NN cord-002542-f7l4ty2j 31 11 of of IN cord-002542-f7l4ty2j 31 12 RNA RNA NNP cord-002542-f7l4ty2j 31 13 viruses virus NNS cord-002542-f7l4ty2j 31 14 as as IN cord-002542-f7l4ty2j 31 15 they -PRON- PRP cord-002542-f7l4ty2j 31 16 provide provide VBP cord-002542-f7l4ty2j 31 17 valuable valuable JJ cord-002542-f7l4ty2j 31 18 tools tool NNS cord-002542-f7l4ty2j 31 19 to to IN cord-002542-f7l4ty2j 31 20 molecular molecular JJ cord-002542-f7l4ty2j 31 21 virologists virologist NNS cord-002542-f7l4ty2j 31 22 by by IN cord-002542-f7l4ty2j 31 23 revealing reveal VBG cord-002542-f7l4ty2j 31 24 conserved conserved JJ cord-002542-f7l4ty2j 31 25 regions region NNS cord-002542-f7l4ty2j 31 26 and and CC cord-002542-f7l4ty2j 31 27 functional functional JJ cord-002542-f7l4ty2j 31 28 domains domain NNS cord-002542-f7l4ty2j 31 29 in in IN cord-002542-f7l4ty2j 31 30 the the DT cord-002542-f7l4ty2j 31 31 RNA RNA NNP cord-002542-f7l4ty2j 31 32 genome genome NN cord-002542-f7l4ty2j 31 33 such such JJ cord-002542-f7l4ty2j 31 34 as as IN cord-002542-f7l4ty2j 31 35 binding bind VBG cord-002542-f7l4ty2j 31 36 sites site NNS cord-002542-f7l4ty2j 31 37 for for IN cord-002542-f7l4ty2j 31 38 viral viral JJ cord-002542-f7l4ty2j 31 39 or or CC cord-002542-f7l4ty2j 31 40 host host NN cord-002542-f7l4ty2j 31 41 factors factor NNS cord-002542-f7l4ty2j 31 42 . . . cord-002542-f7l4ty2j 32 1 Moreover moreover RB cord-002542-f7l4ty2j 32 2 , , , cord-002542-f7l4ty2j 32 3 characterizing characterize VBG cord-002542-f7l4ty2j 32 4 recombination recombination NN cord-002542-f7l4ty2j 32 5 loci locus NNS cord-002542-f7l4ty2j 32 6 reveal reveal VBP cord-002542-f7l4ty2j 32 7 the the DT cord-002542-f7l4ty2j 32 8 mechanisms mechanism NNS cord-002542-f7l4ty2j 32 9 of of IN cord-002542-f7l4ty2j 32 10 recombination recombination NN cord-002542-f7l4ty2j 32 11 , , , cord-002542-f7l4ty2j 32 12 impacting impact VBG cord-002542-f7l4ty2j 32 13 our -PRON- PRP$ cord-002542-f7l4ty2j 32 14 understanding understanding NN cord-002542-f7l4ty2j 32 15 of of IN cord-002542-f7l4ty2j 32 16 viral viral JJ cord-002542-f7l4ty2j 32 17 evolution evolution NN cord-002542-f7l4ty2j 32 18 [ [ -LRB- cord-002542-f7l4ty2j 32 19 8 8 CD cord-002542-f7l4ty2j 32 20 , , , cord-002542-f7l4ty2j 32 21 15 15 CD cord-002542-f7l4ty2j 32 22 , , , cord-002542-f7l4ty2j 32 23 16 16 CD cord-002542-f7l4ty2j 32 24 ] ] -RRB- cord-002542-f7l4ty2j 32 25 . . . cord-002542-f7l4ty2j 33 1 Until until IN cord-002542-f7l4ty2j 33 2 recently recently RB cord-002542-f7l4ty2j 33 3 [ [ -LRB- cord-002542-f7l4ty2j 33 4 17 17 CD cord-002542-f7l4ty2j 33 5 ] ] -RRB- cord-002542-f7l4ty2j 33 6 , , , cord-002542-f7l4ty2j 33 7 due due IN cord-002542-f7l4ty2j 33 8 to to IN cord-002542-f7l4ty2j 33 9 difficulties difficulty NNS cord-002542-f7l4ty2j 33 10 in in IN cord-002542-f7l4ty2j 33 11 capturing capture VBG cord-002542-f7l4ty2j 33 12 and and CC cord-002542-f7l4ty2j 33 13 characterizing characterize VBG cord-002542-f7l4ty2j 33 14 DI DI NNP cord-002542-f7l4ty2j 33 15 - - HYPH cord-002542-f7l4ty2j 33 16 RNAs rna NNS cord-002542-f7l4ty2j 33 17 in in IN cord-002542-f7l4ty2j 33 18 vivo vivo NN cord-002542-f7l4ty2j 33 19 , , , cord-002542-f7l4ty2j 33 20 DI DI NNP cord-002542-f7l4ty2j 33 21 - - HYPH cord-002542-f7l4ty2j 33 22 RNAs rna NNS cord-002542-f7l4ty2j 33 23 were be VBD cord-002542-f7l4ty2j 33 24 considered consider VBN cord-002542-f7l4ty2j 33 25 to to TO cord-002542-f7l4ty2j 33 26 be be VB cord-002542-f7l4ty2j 33 27 a a DT cord-002542-f7l4ty2j 33 28 curious curious JJ cord-002542-f7l4ty2j 33 29 epiphenomenon epiphenomenon NN cord-002542-f7l4ty2j 33 30 of of IN cord-002542-f7l4ty2j 33 31 cell cell NN cord-002542-f7l4ty2j 33 32 - - HYPH cord-002542-f7l4ty2j 33 33 culturing culture VBG cord-002542-f7l4ty2j 33 34 practices practice NNS cord-002542-f7l4ty2j 33 35 . . . cord-002542-f7l4ty2j 34 1 As as IN cord-002542-f7l4ty2j 34 2 a a DT cord-002542-f7l4ty2j 34 3 result result NN cord-002542-f7l4ty2j 34 4 , , , cord-002542-f7l4ty2j 34 5 our -PRON- PRP$ cord-002542-f7l4ty2j 34 6 appreciation appreciation NN cord-002542-f7l4ty2j 34 7 of of IN cord-002542-f7l4ty2j 34 8 the the DT cord-002542-f7l4ty2j 34 9 diversity diversity NN cord-002542-f7l4ty2j 34 10 of of IN cord-002542-f7l4ty2j 34 11 DI DI NNP cord-002542-f7l4ty2j 34 12 - - HYPH cord-002542-f7l4ty2j 34 13 RNAs rna NNS cord-002542-f7l4ty2j 34 14 and and CC cord-002542-f7l4ty2j 34 15 the the DT cord-002542-f7l4ty2j 34 16 range range NN cord-002542-f7l4ty2j 34 17 of of IN cord-002542-f7l4ty2j 34 18 situations situation NNS cord-002542-f7l4ty2j 34 19 in in IN cord-002542-f7l4ty2j 34 20 which which WDT cord-002542-f7l4ty2j 34 21 they -PRON- PRP cord-002542-f7l4ty2j 34 22 could could MD cord-002542-f7l4ty2j 34 23 play play VB cord-002542-f7l4ty2j 34 24 a a DT cord-002542-f7l4ty2j 34 25 role role NN cord-002542-f7l4ty2j 34 26 was be VBD cord-002542-f7l4ty2j 34 27 greatly greatly RB cord-002542-f7l4ty2j 34 28 limited limited JJ cord-002542-f7l4ty2j 34 29 . . . cord-002542-f7l4ty2j 35 1 Increasingly increasingly RB cord-002542-f7l4ty2j 35 2 , , , cord-002542-f7l4ty2j 35 3 due due IN cord-002542-f7l4ty2j 35 4 to to IN cord-002542-f7l4ty2j 35 5 the the DT cord-002542-f7l4ty2j 35 6 use use NN cord-002542-f7l4ty2j 35 7 and and CC cord-002542-f7l4ty2j 35 8 sensitivity sensitivity NN cord-002542-f7l4ty2j 35 9 of of IN cord-002542-f7l4ty2j 35 10 Next Next NNP cord-002542-f7l4ty2j 35 11 - - HYPH cord-002542-f7l4ty2j 35 12 Generation Generation NNP cord-002542-f7l4ty2j 35 13 Sequencing Sequencing NNP cord-002542-f7l4ty2j 35 14 ( ( -LRB- cord-002542-f7l4ty2j 35 15 NGS NGS NNP cord-002542-f7l4ty2j 35 16 ) ) -RRB- cord-002542-f7l4ty2j 35 17 technologies technology NNS cord-002542-f7l4ty2j 35 18 , , , cord-002542-f7l4ty2j 35 19 DI DI NNP cord-002542-f7l4ty2j 35 20 - - HYPH cord-002542-f7l4ty2j 35 21 RNAs rna NNS cord-002542-f7l4ty2j 35 22 have have VBP cord-002542-f7l4ty2j 35 23 been be VBN cord-002542-f7l4ty2j 35 24 observed observe VBN cord-002542-f7l4ty2j 35 25 in in IN cord-002542-f7l4ty2j 35 26 a a DT cord-002542-f7l4ty2j 35 27 multitude multitude NN cord-002542-f7l4ty2j 35 28 of of IN cord-002542-f7l4ty2j 35 29 viral viral JJ cord-002542-f7l4ty2j 35 30 systems system NNS cord-002542-f7l4ty2j 35 31 under under IN cord-002542-f7l4ty2j 35 32 laboratory laboratory NN cord-002542-f7l4ty2j 35 33 conditions condition NNS cord-002542-f7l4ty2j 35 34 ( ( -LRB- cord-002542-f7l4ty2j 35 35 e.g. e.g. IN cord-002542-f7l4ty2j 35 36 SARS SARS NNP cord-002542-f7l4ty2j 35 37 coronavirus coronavirus NN cord-002542-f7l4ty2j 35 38 [ [ -LRB- cord-002542-f7l4ty2j 35 39 18 18 CD cord-002542-f7l4ty2j 35 40 ] ] -RRB- cord-002542-f7l4ty2j 35 41 , , , cord-002542-f7l4ty2j 35 42 HIV HIV NNP cord-002542-f7l4ty2j 35 43 [ [ -LRB- cord-002542-f7l4ty2j 35 44 19 19 CD cord-002542-f7l4ty2j 35 45 ] ] -RRB- cord-002542-f7l4ty2j 35 46 ) ) -RRB- cord-002542-f7l4ty2j 35 47 , , , cord-002542-f7l4ty2j 35 48 in in IN cord-002542-f7l4ty2j 35 49 clinical clinical JJ cord-002542-f7l4ty2j 35 50 settings setting NNS cord-002542-f7l4ty2j 35 51 ( ( -LRB- cord-002542-f7l4ty2j 35 52 e.g. e.g. IN cord-002542-f7l4ty2j 35 53 measles measle NNS cord-002542-f7l4ty2j 35 54 [ [ -LRB- cord-002542-f7l4ty2j 35 55 20 20 CD cord-002542-f7l4ty2j 35 56 ] ] -RRB- cord-002542-f7l4ty2j 35 57 , , , cord-002542-f7l4ty2j 35 58 dengue dengue NN cord-002542-f7l4ty2j 35 59 [ [ -LRB- cord-002542-f7l4ty2j 35 60 21 21 CD cord-002542-f7l4ty2j 35 61 ] ] -RRB- cord-002542-f7l4ty2j 35 62 and and CC cord-002542-f7l4ty2j 35 63 chronic chronic JJ cord-002542-f7l4ty2j 35 64 hepatitis hepatitis NN cord-002542-f7l4ty2j 35 65 C c NN cord-002542-f7l4ty2j 35 66 [ [ -LRB- cord-002542-f7l4ty2j 35 67 22 22 CD cord-002542-f7l4ty2j 35 68 ] ] -RRB- cord-002542-f7l4ty2j 35 69 ) ) -RRB- cord-002542-f7l4ty2j 35 70 and and CC cord-002542-f7l4ty2j 35 71 in in IN cord-002542-f7l4ty2j 35 72 metagenomic metagenomic NNP cord-002542-f7l4ty2j 35 73 or or CC cord-002542-f7l4ty2j 35 74 ' ' `` cord-002542-f7l4ty2j 35 75 wild wild JJ cord-002542-f7l4ty2j 35 76 ' ' '' cord-002542-f7l4ty2j 35 77 samples sample NNS cord-002542-f7l4ty2j 35 78 ( ( -LRB- cord-002542-f7l4ty2j 35 79 e.g. e.g. RB cord-002542-f7l4ty2j 35 80 West West NNP cord-002542-f7l4ty2j 35 81 Nile Nile NNP cord-002542-f7l4ty2j 35 82 virus virus NN cord-002542-f7l4ty2j 35 83 [ [ -LRB- cord-002542-f7l4ty2j 35 84 23 23 CD cord-002542-f7l4ty2j 35 85 ] ] -RRB- cord-002542-f7l4ty2j 35 86 , , , cord-002542-f7l4ty2j 35 87 influenza influenza NN cord-002542-f7l4ty2j 35 88 virus virus NN cord-002542-f7l4ty2j 35 89 [ [ -LRB- cord-002542-f7l4ty2j 35 90 24 24 CD cord-002542-f7l4ty2j 35 91 ] ] -RRB- cord-002542-f7l4ty2j 35 92 ) ) -RRB- cord-002542-f7l4ty2j 35 93 . . . cord-002542-f7l4ty2j 36 1 Despite despite IN cord-002542-f7l4ty2j 36 2 this this DT cord-002542-f7l4ty2j 36 3 burgeoning burgeon VBG cord-002542-f7l4ty2j 36 4 range range NN cord-002542-f7l4ty2j 36 5 of of IN cord-002542-f7l4ty2j 36 6 hosts host NNS cord-002542-f7l4ty2j 36 7 for for IN cord-002542-f7l4ty2j 36 8 DI DI NNP cord-002542-f7l4ty2j 36 9 - - HYPH cord-002542-f7l4ty2j 36 10 RNAs rna NNS cord-002542-f7l4ty2j 36 11 , , , cord-002542-f7l4ty2j 36 12 limitations limitation NNS cord-002542-f7l4ty2j 36 13 in in IN cord-002542-f7l4ty2j 36 14 NGS NGS NNP cord-002542-f7l4ty2j 36 15 technologies technology NNS cord-002542-f7l4ty2j 36 16 including include VBG cord-002542-f7l4ty2j 36 17 high high JJ cord-002542-f7l4ty2j 36 18 artifactual artifactual JJ cord-002542-f7l4ty2j 36 19 recombination recombination NN cord-002542-f7l4ty2j 36 20 rates rate NNS cord-002542-f7l4ty2j 36 21 , , , cord-002542-f7l4ty2j 36 22 short short JJ cord-002542-f7l4ty2j 36 23 reads read NNS cord-002542-f7l4ty2j 36 24 and and CC cord-002542-f7l4ty2j 36 25 a a DT cord-002542-f7l4ty2j 36 26 limited limited JJ cord-002542-f7l4ty2j 36 27 range range NN cord-002542-f7l4ty2j 36 28 of of IN cord-002542-f7l4ty2j 36 29 bioinformatics bioinformatics NN cord-002542-f7l4ty2j 36 30 tools tool NNS cord-002542-f7l4ty2j 36 31 tailored tailor VBN cord-002542-f7l4ty2j 36 32 to to IN cord-002542-f7l4ty2j 36 33 viral viral JJ cord-002542-f7l4ty2j 36 34 RNA RNA NNP cord-002542-f7l4ty2j 36 35 recombination recombination NN cord-002542-f7l4ty2j 36 36 discovery discovery NN cord-002542-f7l4ty2j 36 37 has have VBZ cord-002542-f7l4ty2j 36 38 hindered hinder VBN cord-002542-f7l4ty2j 36 39 our -PRON- PRP$ cord-002542-f7l4ty2j 36 40 ability ability NN cord-002542-f7l4ty2j 36 41 to to TO cord-002542-f7l4ty2j 36 42 detect detect VB cord-002542-f7l4ty2j 36 43 and and CC cord-002542-f7l4ty2j 36 44 characterize characterize VB cord-002542-f7l4ty2j 36 45 DI DI NNP cord-002542-f7l4ty2j 36 46 - - HYPH cord-002542-f7l4ty2j 36 47 RNAs rna NNS cord-002542-f7l4ty2j 36 48 in in IN cord-002542-f7l4ty2j 36 49 complex complex JJ cord-002542-f7l4ty2j 36 50 or or CC cord-002542-f7l4ty2j 36 51 clinical clinical JJ cord-002542-f7l4ty2j 36 52 samples sample NNS cord-002542-f7l4ty2j 36 53 . . . cord-002542-f7l4ty2j 37 1 Flock Flock NNP cord-002542-f7l4ty2j 37 2 House House NNP cord-002542-f7l4ty2j 37 3 virus virus NN cord-002542-f7l4ty2j 37 4 ( ( -LRB- cord-002542-f7l4ty2j 37 5 FHV FHV NNP cord-002542-f7l4ty2j 37 6 ) ) -RRB- cord-002542-f7l4ty2j 37 7 is be VBZ cord-002542-f7l4ty2j 37 8 a a DT cord-002542-f7l4ty2j 37 9 positive positive JJ cord-002542-f7l4ty2j 37 10 - - HYPH cord-002542-f7l4ty2j 37 11 sense sense NN cord-002542-f7l4ty2j 37 12 single single JJ cord-002542-f7l4ty2j 37 13 - - HYPH cord-002542-f7l4ty2j 37 14 stranded strand VBN cord-002542-f7l4ty2j 37 15 RNA RNA NNP cord-002542-f7l4ty2j 37 16 ( ( -LRB- cord-002542-f7l4ty2j 37 17 + + CC cord-002542-f7l4ty2j 37 18 ssRNA ssrna NN cord-002542-f7l4ty2j 37 19 ) ) -RRB- cord-002542-f7l4ty2j 37 20 virus virus NN cord-002542-f7l4ty2j 37 21 originally originally RB cord-002542-f7l4ty2j 37 22 isolated isolate VBN cord-002542-f7l4ty2j 37 23 from from IN cord-002542-f7l4ty2j 37 24 grass grass NN cord-002542-f7l4ty2j 37 25 grubs grub NNS cord-002542-f7l4ty2j 37 26 in in IN cord-002542-f7l4ty2j 37 27 New New NNP cord-002542-f7l4ty2j 37 28 Zealand Zealand NNP cord-002542-f7l4ty2j 37 29 [ [ -LRB- cord-002542-f7l4ty2j 37 30 25 25 CD cord-002542-f7l4ty2j 37 31 ] ] -RRB- cord-002542-f7l4ty2j 37 32 and and CC cord-002542-f7l4ty2j 37 33 is be VBZ cord-002542-f7l4ty2j 37 34 perhaps perhaps RB cord-002542-f7l4ty2j 37 35 the the DT cord-002542-f7l4ty2j 37 36 best well RBS cord-002542-f7l4ty2j 37 37 - - HYPH cord-002542-f7l4ty2j 37 38 studied study VBN cord-002542-f7l4ty2j 37 39 Alphanodavirus Alphanodavirus NNP cord-002542-f7l4ty2j 37 40 from from IN cord-002542-f7l4ty2j 37 41 the the DT cord-002542-f7l4ty2j 37 42 Nodaviridae Nodaviridae NNP cord-002542-f7l4ty2j 37 43 family family NN cord-002542-f7l4ty2j 37 44 . . . cord-002542-f7l4ty2j 38 1 FHV FHV NNP cord-002542-f7l4ty2j 38 2 infects infect VBZ cord-002542-f7l4ty2j 38 3 Drosophila Drosophila NNP cord-002542-f7l4ty2j 38 4 flies fly NNS cord-002542-f7l4ty2j 38 5 and and CC cord-002542-f7l4ty2j 38 6 cells cell NNS cord-002542-f7l4ty2j 38 7 in in IN cord-002542-f7l4ty2j 38 8 culture culture NN cord-002542-f7l4ty2j 38 9 as as RB cord-002542-f7l4ty2j 38 10 well well RB cord-002542-f7l4ty2j 38 11 as as IN cord-002542-f7l4ty2j 38 12 medically medically RB cord-002542-f7l4ty2j 38 13 important important JJ cord-002542-f7l4ty2j 38 14 genera genus NNS cord-002542-f7l4ty2j 38 15 of of IN cord-002542-f7l4ty2j 38 16 insects insect NNS cord-002542-f7l4ty2j 38 17 including include VBG cord-002542-f7l4ty2j 38 18 mosquitos mosquitos NN cord-002542-f7l4ty2j 38 19 , , , cord-002542-f7l4ty2j 38 20 ( ( -LRB- cord-002542-f7l4ty2j 38 21 Anopheles Anopheles NNP cord-002542-f7l4ty2j 38 22 gambiae gambiae NN cord-002542-f7l4ty2j 38 23 ) ) -RRB- cord-002542-f7l4ty2j 38 24 , , , cord-002542-f7l4ty2j 38 25 the the DT cord-002542-f7l4ty2j 38 26 tsetse tsetse NN cord-002542-f7l4ty2j 38 27 fly fly NN cord-002542-f7l4ty2j 38 28 ( ( -LRB- cord-002542-f7l4ty2j 38 29 Glossina Glossina NNP cord-002542-f7l4ty2j 38 30 morsitans morsitan VBD cord-002542-f7l4ty2j 38 31 morsitans morsitans NNP cord-002542-f7l4ty2j 38 32 Westwood Westwood NNP cord-002542-f7l4ty2j 38 33 ) ) -RRB- cord-002542-f7l4ty2j 38 34 , , , cord-002542-f7l4ty2j 38 35 and and CC cord-002542-f7l4ty2j 38 36 the the DT cord-002542-f7l4ty2j 38 37 Chagas Chagas NNP cord-002542-f7l4ty2j 38 38 vector vector NN cord-002542-f7l4ty2j 38 39 ( ( -LRB- cord-002542-f7l4ty2j 38 40 Rhodnius Rhodnius NNP cord-002542-f7l4ty2j 38 41 prolixus prolixus NN cord-002542-f7l4ty2j 38 42 Stal Stal NNP cord-002542-f7l4ty2j 38 43 ) ) -RRB- cord-002542-f7l4ty2j 38 44 [ [ -LRB- cord-002542-f7l4ty2j 38 45 26 26 CD cord-002542-f7l4ty2j 38 46 ] ] -RRB- cord-002542-f7l4ty2j 38 47 . . . cord-002542-f7l4ty2j 39 1 Infection infection NN cord-002542-f7l4ty2j 39 2 of of IN cord-002542-f7l4ty2j 39 3 these these DT cord-002542-f7l4ty2j 39 4 organisms organism NNS cord-002542-f7l4ty2j 39 5 by by IN cord-002542-f7l4ty2j 39 6 FHV FHV NNP cord-002542-f7l4ty2j 39 7 has have VBZ cord-002542-f7l4ty2j 39 8 been be VBN cord-002542-f7l4ty2j 39 9 demonstrated demonstrate VBN cord-002542-f7l4ty2j 39 10 to to TO cord-002542-f7l4ty2j 39 11 have have VB cord-002542-f7l4ty2j 39 12 similar similar JJ cord-002542-f7l4ty2j 39 13 characteristics characteristic NNS cord-002542-f7l4ty2j 39 14 in in IN cord-002542-f7l4ty2j 39 15 terms term NNS cord-002542-f7l4ty2j 39 16 of of IN cord-002542-f7l4ty2j 39 17 viral viral JJ cord-002542-f7l4ty2j 39 18 titer titer NN cord-002542-f7l4ty2j 39 19 , , , cord-002542-f7l4ty2j 39 20 virus virus NN cord-002542-f7l4ty2j 39 21 dissemination dissemination NN cord-002542-f7l4ty2j 39 22 and and CC cord-002542-f7l4ty2j 39 23 mortality mortality NN cord-002542-f7l4ty2j 39 24 as as IN cord-002542-f7l4ty2j 39 25 has have VBZ cord-002542-f7l4ty2j 39 26 been be VBN cord-002542-f7l4ty2j 39 27 shown show VBN cord-002542-f7l4ty2j 39 28 for for IN cord-002542-f7l4ty2j 39 29 fruit fruit NN cord-002542-f7l4ty2j 39 30 fly fly NN cord-002542-f7l4ty2j 39 31 infections infection NNS cord-002542-f7l4ty2j 39 32 . . . cord-002542-f7l4ty2j 40 1 FHV FHV NNP cord-002542-f7l4ty2j 40 2 provides provide VBZ cord-002542-f7l4ty2j 40 3 an an DT cord-002542-f7l4ty2j 40 4 excellent excellent JJ cord-002542-f7l4ty2j 40 5 model model NN cord-002542-f7l4ty2j 40 6 system system NN cord-002542-f7l4ty2j 40 7 to to TO cord-002542-f7l4ty2j 40 8 study study VB cord-002542-f7l4ty2j 40 9 + + CC cord-002542-f7l4ty2j 40 10 ssRNA ssRNA -RRB- cord-002542-f7l4ty2j 40 11 virus virus NN cord-002542-f7l4ty2j 40 12 evolution evolution NN cord-002542-f7l4ty2j 40 13 by by IN cord-002542-f7l4ty2j 40 14 virtue virtue NN cord-002542-f7l4ty2j 40 15 of of IN cord-002542-f7l4ty2j 40 16 having have VBG cord-002542-f7l4ty2j 40 17 one one CD cord-002542-f7l4ty2j 40 18 of of IN cord-002542-f7l4ty2j 40 19 the the DT cord-002542-f7l4ty2j 40 20 smallest smallest RBS cord-002542-f7l4ty2j 40 21 known know VBN cord-002542-f7l4ty2j 40 22 eukaryotic eukaryotic JJ cord-002542-f7l4ty2j 40 23 virus virus NN cord-002542-f7l4ty2j 40 24 genomes genome NNS cord-002542-f7l4ty2j 40 25 [ [ -LRB- cord-002542-f7l4ty2j 40 26 27 27 CD cord-002542-f7l4ty2j 40 27 ] ] -RRB- cord-002542-f7l4ty2j 40 28 . . . cord-002542-f7l4ty2j 41 1 Moreover moreover RB cord-002542-f7l4ty2j 41 2 , , , cord-002542-f7l4ty2j 41 3 the the DT cord-002542-f7l4ty2j 41 4 viral viral JJ cord-002542-f7l4ty2j 41 5 life life NN cord-002542-f7l4ty2j 41 6 - - HYPH cord-002542-f7l4ty2j 41 7 cycle cycle NN cord-002542-f7l4ty2j 41 8 and and CC cord-002542-f7l4ty2j 41 9 details detail NNS cord-002542-f7l4ty2j 41 10 of of IN cord-002542-f7l4ty2j 41 11 the the DT cord-002542-f7l4ty2j 41 12 molecular molecular JJ cord-002542-f7l4ty2j 41 13 biology biology NN cord-002542-f7l4ty2j 41 14 of of IN cord-002542-f7l4ty2j 41 15 virus virus NN cord-002542-f7l4ty2j 41 16 particle particle NN cord-002542-f7l4ty2j 41 17 assembly assembly NN cord-002542-f7l4ty2j 41 18 , , , cord-002542-f7l4ty2j 41 19 cell cell NN cord-002542-f7l4ty2j 41 20 entry entry NN cord-002542-f7l4ty2j 41 21 and and CC cord-002542-f7l4ty2j 41 22 particle particle NN cord-002542-f7l4ty2j 41 23 disassembly disassembly NN cord-002542-f7l4ty2j 41 24 are be VBP cord-002542-f7l4ty2j 41 25 highly highly RB cord-002542-f7l4ty2j 41 26 - - HYPH cord-002542-f7l4ty2j 41 27 characterized characterize VBN cord-002542-f7l4ty2j 41 28 . . . cord-002542-f7l4ty2j 42 1 FHV FHV NNP cord-002542-f7l4ty2j 42 2 contains contain VBZ cord-002542-f7l4ty2j 42 3 two two CD cord-002542-f7l4ty2j 42 4 genomic genomic JJ cord-002542-f7l4ty2j 42 5 RNAs rna NNS cord-002542-f7l4ty2j 42 6 . . . cord-002542-f7l4ty2j 43 1 RNA1 RNA1 NNP cord-002542-f7l4ty2j 43 2 ( ( -LRB- cord-002542-f7l4ty2j 43 3 3107 3107 CD cord-002542-f7l4ty2j 43 4 nts nt NNS cord-002542-f7l4ty2j 43 5 ) ) -RRB- cord-002542-f7l4ty2j 43 6 encodes encode VBZ cord-002542-f7l4ty2j 43 7 the the DT cord-002542-f7l4ty2j 43 8 viral viral JJ cord-002542-f7l4ty2j 43 9 RdRp RdRp NNP cord-002542-f7l4ty2j 43 10 and and CC cord-002542-f7l4ty2j 43 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 43 12 ( ( -LRB- cord-002542-f7l4ty2j 43 13 1400 1400 CD cord-002542-f7l4ty2j 43 14 nts nt NNS cord-002542-f7l4ty2j 43 15 ) ) -RRB- cord-002542-f7l4ty2j 43 16 encodes encode VBZ cord-002542-f7l4ty2j 43 17 the the DT cord-002542-f7l4ty2j 43 18 viral viral JJ cord-002542-f7l4ty2j 43 19 capsid capsid NN cord-002542-f7l4ty2j 43 20 protein protein NN cord-002542-f7l4ty2j 43 21 . . . cord-002542-f7l4ty2j 44 1 RNA1 RNA1 NNP cord-002542-f7l4ty2j 44 2 also also RB cord-002542-f7l4ty2j 44 3 expresses express VBZ cord-002542-f7l4ty2j 44 4 a a DT cord-002542-f7l4ty2j 44 5 small small JJ cord-002542-f7l4ty2j 44 6 sub sub JJ cord-002542-f7l4ty2j 44 7 - - JJ cord-002542-f7l4ty2j 44 8 genomic genomic JJ cord-002542-f7l4ty2j 44 9 RNA RNA NNP cord-002542-f7l4ty2j 44 10 , , , cord-002542-f7l4ty2j 44 11 called call VBN cord-002542-f7l4ty2j 44 12 RNA3 RNA3 NNP cord-002542-f7l4ty2j 44 13 , , , cord-002542-f7l4ty2j 44 14 that that WDT cord-002542-f7l4ty2j 44 15 encodes encode VBZ cord-002542-f7l4ty2j 44 16 the the DT cord-002542-f7l4ty2j 44 17 B2 b2 NN cord-002542-f7l4ty2j 44 18 protein protein NN cord-002542-f7l4ty2j 44 19 responsible responsible JJ cord-002542-f7l4ty2j 44 20 for for IN cord-002542-f7l4ty2j 44 21 inhibition inhibition NN cord-002542-f7l4ty2j 44 22 of of IN cord-002542-f7l4ty2j 44 23 the the DT cord-002542-f7l4ty2j 44 24 anti anti JJ cord-002542-f7l4ty2j 44 25 - - JJ cord-002542-f7l4ty2j 44 26 viral viral JJ cord-002542-f7l4ty2j 44 27 RNAi RNAi NNS cord-002542-f7l4ty2j 44 28 machinery machinery NN cord-002542-f7l4ty2j 44 29 [ [ -LRB- cord-002542-f7l4ty2j 44 30 28 28 CD cord-002542-f7l4ty2j 44 31 ] ] -RRB- cord-002542-f7l4ty2j 44 32 . . . cord-002542-f7l4ty2j 45 1 FHV FHV NNP cord-002542-f7l4ty2j 45 2 has have VBZ cord-002542-f7l4ty2j 45 3 been be VBN cord-002542-f7l4ty2j 45 4 demonstrated demonstrate VBN cord-002542-f7l4ty2j 45 5 to to TO cord-002542-f7l4ty2j 45 6 form form VB cord-002542-f7l4ty2j 45 7 DI DI NNP cord-002542-f7l4ty2j 45 8 - - HYPH cord-002542-f7l4ty2j 45 9 RNAs rna NNS cord-002542-f7l4ty2j 45 10 in in IN cord-002542-f7l4ty2j 45 11 multiple multiple JJ cord-002542-f7l4ty2j 45 12 independent independent JJ cord-002542-f7l4ty2j 45 13 studies study NNS cord-002542-f7l4ty2j 45 14 spanning span VBG cord-002542-f7l4ty2j 45 15 three three CD cord-002542-f7l4ty2j 45 16 decades decade NNS cord-002542-f7l4ty2j 45 17 both both CC cord-002542-f7l4ty2j 45 18 in in IN cord-002542-f7l4ty2j 45 19 cell cell NN cord-002542-f7l4ty2j 45 20 - - HYPH cord-002542-f7l4ty2j 45 21 culture culture NN cord-002542-f7l4ty2j 45 22 [ [ -LRB- cord-002542-f7l4ty2j 45 23 8 8 CD cord-002542-f7l4ty2j 45 24 , , , cord-002542-f7l4ty2j 45 25 26 26 CD cord-002542-f7l4ty2j 45 26 , , , cord-002542-f7l4ty2j 45 27 [ [ -LRB- cord-002542-f7l4ty2j 45 28 29 29 CD cord-002542-f7l4ty2j 45 29 ] ] -RRB- cord-002542-f7l4ty2j 46 1 [ [ -LRB- cord-002542-f7l4ty2j 46 2 30 30 CD cord-002542-f7l4ty2j 46 3 ] ] -RRB- cord-002542-f7l4ty2j 46 4 [ [ -LRB- cord-002542-f7l4ty2j 46 5 31 31 CD cord-002542-f7l4ty2j 46 6 ] ] -RRB- cord-002542-f7l4ty2j 47 1 [ [ -LRB- cord-002542-f7l4ty2j 47 2 32 32 CD cord-002542-f7l4ty2j 47 3 ] ] -RRB- cord-002542-f7l4ty2j 47 4 and and CC cord-002542-f7l4ty2j 47 5 in in IN cord-002542-f7l4ty2j 47 6 Drosophila Drosophila NNP cord-002542-f7l4ty2j 47 7 melanogaster melanogaster NN cord-002542-f7l4ty2j 47 8 [ [ -LRB- cord-002542-f7l4ty2j 47 9 33 33 CD cord-002542-f7l4ty2j 47 10 ] ] -RRB- cord-002542-f7l4ty2j 47 11 . . . cord-002542-f7l4ty2j 48 1 Many many JJ cord-002542-f7l4ty2j 48 2 of of IN cord-002542-f7l4ty2j 48 3 these these DT cord-002542-f7l4ty2j 48 4 studies study NNS cord-002542-f7l4ty2j 48 5 characterized characterize VBD cord-002542-f7l4ty2j 48 6 individual individual JJ cord-002542-f7l4ty2j 48 7 DI DI NNP cord-002542-f7l4ty2j 48 8 - - HYPH cord-002542-f7l4ty2j 48 9 RNA RNA NNP cord-002542-f7l4ty2j 48 10 genomes genome NNS cord-002542-f7l4ty2j 48 11 through through IN cord-002542-f7l4ty2j 48 12 sub sub NN cord-002542-f7l4ty2j 48 13 - - JJ cord-002542-f7l4ty2j 48 14 cloning cloning JJ cord-002542-f7l4ty2j 48 15 and and CC cord-002542-f7l4ty2j 48 16 Sanger Sanger NNP cord-002542-f7l4ty2j 48 17 sequencing sequencing NN cord-002542-f7l4ty2j 48 18 . . . cord-002542-f7l4ty2j 49 1 Intriguingly intriguingly RB cord-002542-f7l4ty2j 49 2 , , , cord-002542-f7l4ty2j 49 3 many many JJ cord-002542-f7l4ty2j 49 4 of of IN cord-002542-f7l4ty2j 49 5 these these DT cord-002542-f7l4ty2j 49 6 DI DI NNP cord-002542-f7l4ty2j 49 7 - - HYPH cord-002542-f7l4ty2j 49 8 RNAs rna NNS cord-002542-f7l4ty2j 49 9 are be VBP cord-002542-f7l4ty2j 49 10 highly highly RB cord-002542-f7l4ty2j 49 11 similar similar JJ cord-002542-f7l4ty2j 49 12 . . . cord-002542-f7l4ty2j 50 1 This this DT cord-002542-f7l4ty2j 50 2 indicates indicate VBZ cord-002542-f7l4ty2j 50 3 that that IN cord-002542-f7l4ty2j 50 4 either either CC cord-002542-f7l4ty2j 50 5 the the DT cord-002542-f7l4ty2j 50 6 DI DI NNP cord-002542-f7l4ty2j 50 7 - - HYPH cord-002542-f7l4ty2j 50 8 RNAs rna NNS cord-002542-f7l4ty2j 50 9 have have VBP cord-002542-f7l4ty2j 50 10 emerged emerge VBN cord-002542-f7l4ty2j 50 11 due due IN cord-002542-f7l4ty2j 50 12 to to IN cord-002542-f7l4ty2j 50 13 a a DT cord-002542-f7l4ty2j 50 14 common common JJ cord-002542-f7l4ty2j 50 15 mechanism mechanism NN cord-002542-f7l4ty2j 50 16 of of IN cord-002542-f7l4ty2j 50 17 formation formation NN cord-002542-f7l4ty2j 50 18 or or CC cord-002542-f7l4ty2j 50 19 the the DT cord-002542-f7l4ty2j 50 20 presence presence NN cord-002542-f7l4ty2j 50 21 of of IN cord-002542-f7l4ty2j 50 22 a a DT cord-002542-f7l4ty2j 50 23 common common JJ cord-002542-f7l4ty2j 50 24 selectivity selectivity NN cord-002542-f7l4ty2j 50 25 filter filter NN cord-002542-f7l4ty2j 50 26 , , , cord-002542-f7l4ty2j 50 27 or or CC cord-002542-f7l4ty2j 50 28 both both DT cord-002542-f7l4ty2j 50 29 . . . cord-002542-f7l4ty2j 51 1 Our -PRON- PRP$ cord-002542-f7l4ty2j 51 2 recent recent JJ cord-002542-f7l4ty2j 51 3 NGS NGS NNP cord-002542-f7l4ty2j 51 4 studies study NNS cord-002542-f7l4ty2j 51 5 of of IN cord-002542-f7l4ty2j 51 6 RNA RNA NNP cord-002542-f7l4ty2j 51 7 recombination recombination NN cord-002542-f7l4ty2j 51 8 in in IN cord-002542-f7l4ty2j 51 9 FHV FHV NNP cord-002542-f7l4ty2j 51 10 revealed reveal VBD cord-002542-f7l4ty2j 51 11 a a DT cord-002542-f7l4ty2j 51 12 diverse diverse JJ cord-002542-f7l4ty2j 51 13 array array NN cord-002542-f7l4ty2j 51 14 of of IN cord-002542-f7l4ty2j 51 15 RNA rna NN cord-002542-f7l4ty2j 51 16 recombination recombination NN cord-002542-f7l4ty2j 51 17 events event NNS cord-002542-f7l4ty2j 51 18 , , , cord-002542-f7l4ty2j 51 19 suggesting suggest VBG cord-002542-f7l4ty2j 51 20 that that IN cord-002542-f7l4ty2j 51 21 the the DT cord-002542-f7l4ty2j 51 22 genomic genomic JJ cord-002542-f7l4ty2j 51 23 landscape landscape NN cord-002542-f7l4ty2j 51 24 of of IN cord-002542-f7l4ty2j 51 25 DI DI NNP cord-002542-f7l4ty2j 51 26 - - HYPH cord-002542-f7l4ty2j 51 27 RNAs RNAs NNPS cord-002542-f7l4ty2j 51 28 is be VBZ cord-002542-f7l4ty2j 51 29 highly highly RB cord-002542-f7l4ty2j 51 30 dynamic dynamic JJ cord-002542-f7l4ty2j 51 31 and and CC cord-002542-f7l4ty2j 51 32 likely likely RB cord-002542-f7l4ty2j 51 33 contributes contribute VBZ cord-002542-f7l4ty2j 51 34 significantly significantly RB cord-002542-f7l4ty2j 51 35 to to IN cord-002542-f7l4ty2j 51 36 the the DT cord-002542-f7l4ty2j 51 37 diversity diversity NN cord-002542-f7l4ty2j 51 38 of of IN cord-002542-f7l4ty2j 51 39 viral viral JJ cord-002542-f7l4ty2j 51 40 genomes genome NNS cord-002542-f7l4ty2j 51 41 that that WDT cord-002542-f7l4ty2j 51 42 form form VBP cord-002542-f7l4ty2j 51 43 the the DT cord-002542-f7l4ty2j 51 44 viral viral JJ cord-002542-f7l4ty2j 51 45 quasi quasi JJ cord-002542-f7l4ty2j 51 46 - - NN cord-002542-f7l4ty2j 51 47 species species JJ cord-002542-f7l4ty2j 51 48 [ [ -LRB- cord-002542-f7l4ty2j 51 49 34 34 CD cord-002542-f7l4ty2j 51 50 ] ] -RRB- cord-002542-f7l4ty2j 51 51 . . . cord-002542-f7l4ty2j 52 1 Despite despite IN cord-002542-f7l4ty2j 52 2 these these DT cord-002542-f7l4ty2j 52 3 findings finding NNS cord-002542-f7l4ty2j 52 4 , , , cord-002542-f7l4ty2j 52 5 studies study NNS cord-002542-f7l4ty2j 52 6 to to IN cord-002542-f7l4ty2j 52 7 - - HYPH cord-002542-f7l4ty2j 52 8 date date NN cord-002542-f7l4ty2j 52 9 present present NN cord-002542-f7l4ty2j 52 10 only only RB cord-002542-f7l4ty2j 52 11 a a DT cord-002542-f7l4ty2j 52 12 single single JJ cord-002542-f7l4ty2j 52 13 snap snap NN cord-002542-f7l4ty2j 52 14 - - HYPH cord-002542-f7l4ty2j 52 15 shot shot NN cord-002542-f7l4ty2j 52 16 of of IN cord-002542-f7l4ty2j 52 17 the the DT cord-002542-f7l4ty2j 52 18 DI DI NNP cord-002542-f7l4ty2j 52 19 - - HYPH cord-002542-f7l4ty2j 52 20 RNA RNA NNP cord-002542-f7l4ty2j 52 21 genome genome NN cord-002542-f7l4ty2j 52 22 landscape landscape NN cord-002542-f7l4ty2j 52 23 and and CC cord-002542-f7l4ty2j 52 24 do do VBP cord-002542-f7l4ty2j 52 25 not not RB cord-002542-f7l4ty2j 52 26 capture capture VB cord-002542-f7l4ty2j 52 27 the the DT cord-002542-f7l4ty2j 52 28 pathways pathway NNS cord-002542-f7l4ty2j 52 29 of of IN cord-002542-f7l4ty2j 52 30 their -PRON- PRP$ cord-002542-f7l4ty2j 52 31 emergence emergence NN cord-002542-f7l4ty2j 52 32 and and CC cord-002542-f7l4ty2j 52 33 evolution evolution NN cord-002542-f7l4ty2j 52 34 nor nor CC cord-002542-f7l4ty2j 52 35 characterize characterize VB cord-002542-f7l4ty2j 52 36 any any DT cord-002542-f7l4ty2j 52 37 intermediate intermediate JJ cord-002542-f7l4ty2j 52 38 DI DI NNP cord-002542-f7l4ty2j 52 39 - - HYPH cord-002542-f7l4ty2j 52 40 RNA RNA NNP cord-002542-f7l4ty2j 52 41 species specie NNS cord-002542-f7l4ty2j 52 42 that that WDT cord-002542-f7l4ty2j 52 43 might may MD cord-002542-f7l4ty2j 52 44 arise arise VB cord-002542-f7l4ty2j 52 45 during during IN cord-002542-f7l4ty2j 52 46 these these DT cord-002542-f7l4ty2j 52 47 processes process NNS cord-002542-f7l4ty2j 52 48 . . . cord-002542-f7l4ty2j 53 1 In in IN cord-002542-f7l4ty2j 53 2 order order NN cord-002542-f7l4ty2j 53 3 to to TO cord-002542-f7l4ty2j 53 4 resolve resolve VB cord-002542-f7l4ty2j 53 5 the the DT cord-002542-f7l4ty2j 53 6 potential potential JJ cord-002542-f7l4ty2j 53 7 mechanisms mechanism NNS cord-002542-f7l4ty2j 53 8 of of IN cord-002542-f7l4ty2j 53 9 DI DI NNP cord-002542-f7l4ty2j 53 10 - - HYPH cord-002542-f7l4ty2j 53 11 RNA RNA NNP cord-002542-f7l4ty2j 53 12 emergence emergence NN cord-002542-f7l4ty2j 53 13 and and CC cord-002542-f7l4ty2j 53 14 elucidate elucidate VB cord-002542-f7l4ty2j 53 15 the the DT cord-002542-f7l4ty2j 53 16 evolutionary evolutionary JJ cord-002542-f7l4ty2j 53 17 pathways pathway NNS cord-002542-f7l4ty2j 53 18 that that WDT cord-002542-f7l4ty2j 53 19 lead lead VBP cord-002542-f7l4ty2j 53 20 to to IN cord-002542-f7l4ty2j 53 21 the the DT cord-002542-f7l4ty2j 53 22 formation formation NN cord-002542-f7l4ty2j 53 23 of of IN cord-002542-f7l4ty2j 53 24 ' ' `` cord-002542-f7l4ty2j 53 25 mature mature JJ cord-002542-f7l4ty2j 53 26 ' ' '' cord-002542-f7l4ty2j 53 27 DI di NN cord-002542-f7l4ty2j 53 28 - - HYPH cord-002542-f7l4ty2j 53 29 RNAs rna NNS cord-002542-f7l4ty2j 53 30 , , , cord-002542-f7l4ty2j 53 31 we -PRON- PRP cord-002542-f7l4ty2j 53 32 performed perform VBD cord-002542-f7l4ty2j 53 33 high high JJ cord-002542-f7l4ty2j 53 34 - - HYPH cord-002542-f7l4ty2j 53 35 titer titer NN cord-002542-f7l4ty2j 53 36 serial serial JJ cord-002542-f7l4ty2j 53 37 passaging passaging NN cord-002542-f7l4ty2j 53 38 of of IN cord-002542-f7l4ty2j 53 39 FHV FHV NNP cord-002542-f7l4ty2j 53 40 in in IN cord-002542-f7l4ty2j 53 41 cell cell NN cord-002542-f7l4ty2j 53 42 culture culture NN cord-002542-f7l4ty2j 53 43 and and CC cord-002542-f7l4ty2j 53 44 characterized characterize VBD cord-002542-f7l4ty2j 53 45 the the DT cord-002542-f7l4ty2j 53 46 encapsidated encapsidate VBN cord-002542-f7l4ty2j 53 47 RNA RNA NNP cord-002542-f7l4ty2j 53 48 using use VBG cord-002542-f7l4ty2j 53 49 RNAseq RNAseq NNP cord-002542-f7l4ty2j 53 50 . . . cord-002542-f7l4ty2j 54 1 We -PRON- PRP cord-002542-f7l4ty2j 54 2 used use VBD cord-002542-f7l4ty2j 54 3 Illumina Illumina NNP cord-002542-f7l4ty2j 54 4 HiSeq HiSeq NNP cord-002542-f7l4ty2j 54 5 sequencing sequencing NN cord-002542-f7l4ty2j 54 6 of of IN cord-002542-f7l4ty2j 54 7 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 54 8 generated generate VBD cord-002542-f7l4ty2j 54 9 libraries library NNS cord-002542-f7l4ty2j 54 10 to to TO cord-002542-f7l4ty2j 54 11 provide provide VB cord-002542-f7l4ty2j 54 12 a a DT cord-002542-f7l4ty2j 54 13 high high JJ cord-002542-f7l4ty2j 54 14 - - HYPH cord-002542-f7l4ty2j 54 15 resolution resolution NN cord-002542-f7l4ty2j 54 16 and and CC cord-002542-f7l4ty2j 54 17 high high JJ cord-002542-f7l4ty2j 54 18 - - HYPH cord-002542-f7l4ty2j 54 19 confidence confidence NN cord-002542-f7l4ty2j 54 20 quantification quantification NN cord-002542-f7l4ty2j 54 21 of of IN cord-002542-f7l4ty2j 54 22 individual individual JJ cord-002542-f7l4ty2j 54 23 recombination recombination NN cord-002542-f7l4ty2j 54 24 events event NNS cord-002542-f7l4ty2j 54 25 . . . cord-002542-f7l4ty2j 55 1 We -PRON- PRP cord-002542-f7l4ty2j 55 2 combined combine VBD cord-002542-f7l4ty2j 55 3 this this DT cord-002542-f7l4ty2j 55 4 information information NN cord-002542-f7l4ty2j 55 5 with with IN cord-002542-f7l4ty2j 55 6 long long RB cord-002542-f7l4ty2j 55 7 - - HYPH cord-002542-f7l4ty2j 55 8 read read VBN cord-002542-f7l4ty2j 55 9 Oxford Oxford NNP cord-002542-f7l4ty2j 55 10 Nanopore Nanopore NNP cord-002542-f7l4ty2j 55 11 Technologies Technologies NNP cord-002542-f7l4ty2j 55 12 's 's POS cord-002542-f7l4ty2j 55 13 ( ( -LRB- cord-002542-f7l4ty2j 55 14 ONT ONT NNP cord-002542-f7l4ty2j 55 15 ) ) -RRB- cord-002542-f7l4ty2j 55 16 MinION minion NN cord-002542-f7l4ty2j 55 17 sequencing sequencing NN cord-002542-f7l4ty2j 55 18 to to TO cord-002542-f7l4ty2j 55 19 resolve resolve VB cord-002542-f7l4ty2j 55 20 the the DT cord-002542-f7l4ty2j 55 21 topology topology NN cord-002542-f7l4ty2j 55 22 of of IN cord-002542-f7l4ty2j 55 23 full full JJ cord-002542-f7l4ty2j 55 24 - - HYPH cord-002542-f7l4ty2j 55 25 length length NN cord-002542-f7l4ty2j 55 26 and and CC cord-002542-f7l4ty2j 55 27 defective defective JJ cord-002542-f7l4ty2j 55 28 RNA RNA NNP cord-002542-f7l4ty2j 55 29 genomes genome NNS cord-002542-f7l4ty2j 55 30 . . . cord-002542-f7l4ty2j 56 1 By by IN cord-002542-f7l4ty2j 56 2 combining combine VBG cord-002542-f7l4ty2j 56 3 these these DT cord-002542-f7l4ty2j 56 4 data datum NNS cord-002542-f7l4ty2j 56 5 , , , cord-002542-f7l4ty2j 56 6 we -PRON- PRP cord-002542-f7l4ty2j 56 7 aimed aim VBD cord-002542-f7l4ty2j 56 8 to to TO cord-002542-f7l4ty2j 56 9 determine determine VB cord-002542-f7l4ty2j 56 10 the the DT cord-002542-f7l4ty2j 56 11 correlation correlation NN cord-002542-f7l4ty2j 56 12 of of IN cord-002542-f7l4ty2j 56 13 recombination recombination NN cord-002542-f7l4ty2j 56 14 events event NNS cord-002542-f7l4ty2j 56 15 within within IN cord-002542-f7l4ty2j 56 16 single single JJ cord-002542-f7l4ty2j 56 17 RNA RNA NNP cord-002542-f7l4ty2j 56 18 virus virus NN cord-002542-f7l4ty2j 56 19 genomes genome NNS cord-002542-f7l4ty2j 56 20 , , , cord-002542-f7l4ty2j 56 21 characterize characterize VB cord-002542-f7l4ty2j 56 22 the the DT cord-002542-f7l4ty2j 56 23 distribution distribution NN cord-002542-f7l4ty2j 56 24 of of IN cord-002542-f7l4ty2j 56 25 defective defective JJ cord-002542-f7l4ty2j 56 26 RNA RNA NNP cord-002542-f7l4ty2j 56 27 genomes genome NNS cord-002542-f7l4ty2j 56 28 , , , cord-002542-f7l4ty2j 56 29 and and CC cord-002542-f7l4ty2j 56 30 determine determine VB cord-002542-f7l4ty2j 56 31 the the DT cord-002542-f7l4ty2j 56 32 exact exact JJ cord-002542-f7l4ty2j 56 33 make make NN cord-002542-f7l4ty2j 56 34 - - HYPH cord-002542-f7l4ty2j 56 35 up up NN cord-002542-f7l4ty2j 56 36 of of IN cord-002542-f7l4ty2j 56 37 DI DI NNP cord-002542-f7l4ty2j 56 38 - - HYPH cord-002542-f7l4ty2j 56 39 RNAs rna NNS cord-002542-f7l4ty2j 56 40 during during IN cord-002542-f7l4ty2j 56 41 serial serial JJ cord-002542-f7l4ty2j 56 42 passaging passaging NN cord-002542-f7l4ty2j 56 43 of of IN cord-002542-f7l4ty2j 56 44 FHV FHV NNP cord-002542-f7l4ty2j 56 45 in in IN cord-002542-f7l4ty2j 56 46 cell cell NN cord-002542-f7l4ty2j 56 47 culture culture NN cord-002542-f7l4ty2j 56 48 . . . cord-002542-f7l4ty2j 57 1 We -PRON- PRP cord-002542-f7l4ty2j 57 2 recently recently RB cord-002542-f7l4ty2j 57 3 developed develop VBD cord-002542-f7l4ty2j 57 4 the the DT cord-002542-f7l4ty2j 57 5 ' ' `` cord-002542-f7l4ty2j 57 6 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 57 7 ' ' '' cord-002542-f7l4ty2j 57 8 method method NN cord-002542-f7l4ty2j 57 9 for for IN cord-002542-f7l4ty2j 57 10 RNAseq RNAseq NNP cord-002542-f7l4ty2j 57 11 that that WDT cord-002542-f7l4ty2j 57 12 uses use VBZ cord-002542-f7l4ty2j 57 13 copper copper NN cord-002542-f7l4ty2j 57 14 - - HYPH cord-002542-f7l4ty2j 57 15 catalyzed catalyze VBN cord-002542-f7l4ty2j 57 16 alkyne alkyne NN cord-002542-f7l4ty2j 57 17 - - HYPH cord-002542-f7l4ty2j 57 18 azide azide NN cord-002542-f7l4ty2j 57 19 cycloaddition cycloaddition NN cord-002542-f7l4ty2j 57 20 ( ( -LRB- cord-002542-f7l4ty2j 57 21 CuAAC CuAAC NNP cord-002542-f7l4ty2j 57 22 ) ) -RRB- cord-002542-f7l4ty2j 57 23 , , , cord-002542-f7l4ty2j 57 24 a a DT cord-002542-f7l4ty2j 57 25 click click VB cord-002542-f7l4ty2j 57 26 - - HYPH cord-002542-f7l4ty2j 57 27 chemistry chemistry NN cord-002542-f7l4ty2j 57 28 reaction reaction NN cord-002542-f7l4ty2j 57 29 , , , cord-002542-f7l4ty2j 57 30 for for IN cord-002542-f7l4ty2j 57 31 RNAseq rnaseq NN cord-002542-f7l4ty2j 57 32 library library NN cord-002542-f7l4ty2j 57 33 synthesis synthesis NN cord-002542-f7l4ty2j 57 34 [ [ -LRB- cord-002542-f7l4ty2j 57 35 35 35 CD cord-002542-f7l4ty2j 57 36 ] ] -RRB- cord-002542-f7l4ty2j 57 37 . . . cord-002542-f7l4ty2j 58 1 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 58 2 provides provide VBZ cord-002542-f7l4ty2j 58 3 a a DT cord-002542-f7l4ty2j 58 4 robust robust JJ cord-002542-f7l4ty2j 58 5 platform platform NN cord-002542-f7l4ty2j 58 6 on on IN cord-002542-f7l4ty2j 58 7 which which WDT cord-002542-f7l4ty2j 58 8 to to TO cord-002542-f7l4ty2j 58 9 study study VB cord-002542-f7l4ty2j 58 10 RNA RNA NNP cord-002542-f7l4ty2j 58 11 recombination recombination NN cord-002542-f7l4ty2j 58 12 in in IN cord-002542-f7l4ty2j 58 13 RNA RNA NNP cord-002542-f7l4ty2j 58 14 viruses virus NNS cord-002542-f7l4ty2j 58 15 . . . cord-002542-f7l4ty2j 59 1 Artifactual artifactual JJ cord-002542-f7l4ty2j 59 2 recombination recombination NN cord-002542-f7l4ty2j 59 3 is be VBZ cord-002542-f7l4ty2j 59 4 a a DT cord-002542-f7l4ty2j 59 5 common common JJ cord-002542-f7l4ty2j 59 6 contaminant contaminant NN cord-002542-f7l4ty2j 59 7 in in IN cord-002542-f7l4ty2j 59 8 NGS NGS NNP cord-002542-f7l4ty2j 59 9 library library NN cord-002542-f7l4ty2j 59 10 generation generation NN cord-002542-f7l4ty2j 59 11 and and CC cord-002542-f7l4ty2j 59 12 can can MD cord-002542-f7l4ty2j 59 13 easily easily RB cord-002542-f7l4ty2j 59 14 obscure obscure VB cord-002542-f7l4ty2j 59 15 rare rare JJ cord-002542-f7l4ty2j 59 16 or or CC cord-002542-f7l4ty2j 59 17 non non JJ cord-002542-f7l4ty2j 59 18 - - JJ cord-002542-f7l4ty2j 59 19 canonical canonical JJ cord-002542-f7l4ty2j 59 20 recombinant recombinant JJ cord-002542-f7l4ty2j 59 21 species specie NNS cord-002542-f7l4ty2j 59 22 . . . cord-002542-f7l4ty2j 60 1 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 60 2 does do VBZ cord-002542-f7l4ty2j 60 3 not not RB cord-002542-f7l4ty2j 60 4 require require VB cord-002542-f7l4ty2j 60 5 template template NN cord-002542-f7l4ty2j 60 6 fragmentation fragmentation NN cord-002542-f7l4ty2j 60 7 and and CC cord-002542-f7l4ty2j 60 8 replaces replace VBZ cord-002542-f7l4ty2j 60 9 enzymatic enzymatic JJ cord-002542-f7l4ty2j 60 10 ligation ligation NN cord-002542-f7l4ty2j 60 11 steps step NNS cord-002542-f7l4ty2j 60 12 commonly commonly RB cord-002542-f7l4ty2j 60 13 required require VBN cord-002542-f7l4ty2j 60 14 in in IN cord-002542-f7l4ty2j 60 15 NGS NGS NNP cord-002542-f7l4ty2j 60 16 library library NN cord-002542-f7l4ty2j 60 17 generation generation NN cord-002542-f7l4ty2j 60 18 with with IN cord-002542-f7l4ty2j 60 19 click click NN cord-002542-f7l4ty2j 60 20 - - HYPH cord-002542-f7l4ty2j 60 21 chemistry chemistry NN cord-002542-f7l4ty2j 60 22 . . . cord-002542-f7l4ty2j 61 1 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 61 2 works work VBZ cord-002542-f7l4ty2j 61 3 by by IN cord-002542-f7l4ty2j 61 4 introducing introduce VBG cord-002542-f7l4ty2j 61 5 small small JJ cord-002542-f7l4ty2j 61 6 amounts amount NNS cord-002542-f7l4ty2j 61 7 of of IN cord-002542-f7l4ty2j 61 8 azido azido NN cord-002542-f7l4ty2j 61 9 - - HYPH cord-002542-f7l4ty2j 61 10 nucleotides nucleotide NNS cord-002542-f7l4ty2j 61 11 ( ( -LRB- cord-002542-f7l4ty2j 61 12 AzNTPs AzNTPs NNP cord-002542-f7l4ty2j 61 13 ) ) -RRB- cord-002542-f7l4ty2j 61 14 into into IN cord-002542-f7l4ty2j 61 15 RT RT NNP cord-002542-f7l4ty2j 61 16 - - HYPH cord-002542-f7l4ty2j 61 17 PCR PCR NNP cord-002542-f7l4ty2j 61 18 reactions reaction NNS cord-002542-f7l4ty2j 61 19 to to TO cord-002542-f7l4ty2j 61 20 generate generate VB cord-002542-f7l4ty2j 61 21 azido azido NNP cord-002542-f7l4ty2j 61 22 - - HYPH cord-002542-f7l4ty2j 61 23 terminated terminate VBN cord-002542-f7l4ty2j 61 24 cDNA cdna NN cord-002542-f7l4ty2j 61 25 transcripts transcript NNS cord-002542-f7l4ty2j 61 26 . . . cord-002542-f7l4ty2j 62 1 These these DT cord-002542-f7l4ty2j 62 2 cDNA cdna NN cord-002542-f7l4ty2j 62 3 fragments fragment NNS cord-002542-f7l4ty2j 62 4 are be VBP cord-002542-f7l4ty2j 62 5 subsequently subsequently RB cord-002542-f7l4ty2j 62 6 mixed mix VBN cord-002542-f7l4ty2j 62 7 with with IN cord-002542-f7l4ty2j 62 8 alkyne alkyne NN cord-002542-f7l4ty2j 62 9 - - HYPH cord-002542-f7l4ty2j 62 10 labelled label VBN cord-002542-f7l4ty2j 62 11 DNA dna NN cord-002542-f7l4ty2j 62 12 adaptors adaptor NNS cord-002542-f7l4ty2j 62 13 . . . cord-002542-f7l4ty2j 63 1 The the DT cord-002542-f7l4ty2j 63 2 addition addition NN cord-002542-f7l4ty2j 63 3 of of IN cord-002542-f7l4ty2j 63 4 a a DT cord-002542-f7l4ty2j 63 5 copper copper NN cord-002542-f7l4ty2j 63 6 catalyst catalyst NN cord-002542-f7l4ty2j 63 7 results result NNS cord-002542-f7l4ty2j 63 8 in in IN cord-002542-f7l4ty2j 63 9 the the DT cord-002542-f7l4ty2j 63 10 ' ' `` cord-002542-f7l4ty2j 63 11 click click NN cord-002542-f7l4ty2j 63 12 - - HYPH cord-002542-f7l4ty2j 63 13 ligation ligation NN cord-002542-f7l4ty2j 63 14 ' ' '' cord-002542-f7l4ty2j 63 15 of of IN cord-002542-f7l4ty2j 63 16 the the DT cord-002542-f7l4ty2j 63 17 two two CD cord-002542-f7l4ty2j 63 18 chemically chemically RB cord-002542-f7l4ty2j 63 19 - - HYPH cord-002542-f7l4ty2j 63 20 functionalized functionalize VBN cord-002542-f7l4ty2j 63 21 DNA dna NN cord-002542-f7l4ty2j 63 22 substrates substrate NNS cord-002542-f7l4ty2j 63 23 to to TO cord-002542-f7l4ty2j 63 24 produce produce VB cord-002542-f7l4ty2j 63 25 an an DT cord-002542-f7l4ty2j 63 26 unnatural unnatural JJ cord-002542-f7l4ty2j 63 27 triazole triazole NN cord-002542-f7l4ty2j 63 28 - - HYPH cord-002542-f7l4ty2j 63 29 linked link VBN cord-002542-f7l4ty2j 63 30 single single RB cord-002542-f7l4ty2j 63 31 - - HYPH cord-002542-f7l4ty2j 63 32 stranded strand VBN cord-002542-f7l4ty2j 63 33 DNA dna NN cord-002542-f7l4ty2j 63 34 molecule molecule NN cord-002542-f7l4ty2j 63 35 [ [ -LRB- cord-002542-f7l4ty2j 63 36 36 36 CD cord-002542-f7l4ty2j 63 37 ] ] -RRB- cord-002542-f7l4ty2j 63 38 . . . cord-002542-f7l4ty2j 64 1 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 64 2 prevents prevent VBZ cord-002542-f7l4ty2j 64 3 template template NN cord-002542-f7l4ty2j 64 4 switching switch VBG cord-002542-f7l4ty2j 64 5 during during IN cord-002542-f7l4ty2j 64 6 RT RT NNP cord-002542-f7l4ty2j 64 7 - - HYPH cord-002542-f7l4ty2j 64 8 PCR PCR NNP cord-002542-f7l4ty2j 64 9 as as RB cord-002542-f7l4ty2j 64 10 well well RB cord-002542-f7l4ty2j 64 11 as as IN cord-002542-f7l4ty2j 64 12 non non JJ cord-002542-f7l4ty2j 64 13 - - JJ cord-002542-f7l4ty2j 64 14 specific specific JJ cord-002542-f7l4ty2j 64 15 ligation ligation NN cord-002542-f7l4ty2j 64 16 of of IN cord-002542-f7l4ty2j 64 17 RNA RNA NNP cord-002542-f7l4ty2j 64 18 fragments fragment NNS cord-002542-f7l4ty2j 64 19 . . . cord-002542-f7l4ty2j 65 1 We -PRON- PRP cord-002542-f7l4ty2j 65 2 demonstrated demonstrate VBD cord-002542-f7l4ty2j 65 3 that that IN cord-002542-f7l4ty2j 65 4 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 65 5 reduces reduce VBZ cord-002542-f7l4ty2j 65 6 artifactual artifactual JJ cord-002542-f7l4ty2j 65 7 recombination recombination NN cord-002542-f7l4ty2j 65 8 to to IN cord-002542-f7l4ty2j 65 9 fewer few JJR cord-002542-f7l4ty2j 65 10 than than IN cord-002542-f7l4ty2j 65 11 3 3 CD cord-002542-f7l4ty2j 65 12 events event NNS cord-002542-f7l4ty2j 65 13 per per IN cord-002542-f7l4ty2j 65 14 million million CD cord-002542-f7l4ty2j 65 15 mapped mapped NNS cord-002542-f7l4ty2j 65 16 reads read VBZ cord-002542-f7l4ty2j 65 17 [ [ -LRB- cord-002542-f7l4ty2j 65 18 35 35 CD cord-002542-f7l4ty2j 65 19 ] ] -RRB- cord-002542-f7l4ty2j 65 20 . . . cord-002542-f7l4ty2j 66 1 As as IN cord-002542-f7l4ty2j 66 2 a a DT cord-002542-f7l4ty2j 66 3 result result NN cord-002542-f7l4ty2j 66 4 , , , cord-002542-f7l4ty2j 66 5 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 66 6 provides provide VBZ cord-002542-f7l4ty2j 66 7 a a DT cord-002542-f7l4ty2j 66 8 superior superior JJ cord-002542-f7l4ty2j 66 9 method method NN cord-002542-f7l4ty2j 66 10 for for IN cord-002542-f7l4ty2j 66 11 the the DT cord-002542-f7l4ty2j 66 12 detection detection NN cord-002542-f7l4ty2j 66 13 of of IN cord-002542-f7l4ty2j 66 14 DI DI NNP cord-002542-f7l4ty2j 66 15 - - HYPH cord-002542-f7l4ty2j 66 16 RNAs RNAs NNPS cord-002542-f7l4ty2j 66 17 and and CC cord-002542-f7l4ty2j 66 18 RNA RNA NNP cord-002542-f7l4ty2j 66 19 recombination recombination NN cord-002542-f7l4ty2j 66 20 events event NNS cord-002542-f7l4ty2j 66 21 . . . cord-002542-f7l4ty2j 67 1 The the DT cord-002542-f7l4ty2j 67 2 Oxford Oxford NNP cord-002542-f7l4ty2j 67 3 Nanopore Nanopore NNP cord-002542-f7l4ty2j 67 4 Technologies Technologies NNPS cord-002542-f7l4ty2j 67 5 's 's POS cord-002542-f7l4ty2j 67 6 ( ( -LRB- cord-002542-f7l4ty2j 67 7 ONT ONT NNP cord-002542-f7l4ty2j 67 8 ) ) -RRB- cord-002542-f7l4ty2j 67 9 MinION MinION NNP cord-002542-f7l4ty2j 67 10 is be VBZ cord-002542-f7l4ty2j 67 11 a a DT cord-002542-f7l4ty2j 67 12 small small JJ cord-002542-f7l4ty2j 67 13 handheld handheld JJ cord-002542-f7l4ty2j 67 14 sequencing sequencing NN cord-002542-f7l4ty2j 67 15 device device NN cord-002542-f7l4ty2j 67 16 [ [ -LRB- cord-002542-f7l4ty2j 67 17 37 37 CD cord-002542-f7l4ty2j 67 18 ] ] -RRB- cord-002542-f7l4ty2j 67 19 poised poise VBN cord-002542-f7l4ty2j 67 20 to to TO cord-002542-f7l4ty2j 67 21 revolutionize revolutionize VB cord-002542-f7l4ty2j 67 22 the the DT cord-002542-f7l4ty2j 67 23 next next JJ cord-002542-f7l4ty2j 67 24 - - HYPH cord-002542-f7l4ty2j 67 25 generation generation NN cord-002542-f7l4ty2j 67 26 sequencing sequencing NN cord-002542-f7l4ty2j 67 27 field field NN cord-002542-f7l4ty2j 67 28 by by IN cord-002542-f7l4ty2j 67 29 providing provide VBG cord-002542-f7l4ty2j 67 30 realtime realtime NN cord-002542-f7l4ty2j 67 31 , , , cord-002542-f7l4ty2j 67 32 high high JJ cord-002542-f7l4ty2j 67 33 - - HYPH cord-002542-f7l4ty2j 67 34 throughput throughput NN cord-002542-f7l4ty2j 67 35 and and CC cord-002542-f7l4ty2j 67 36 long long JJ cord-002542-f7l4ty2j 67 37 - - HYPH cord-002542-f7l4ty2j 67 38 range range NN cord-002542-f7l4ty2j 67 39 ( ( -LRB- cord-002542-f7l4ty2j 67 40 over over IN cord-002542-f7l4ty2j 67 41 882 882 CD cord-002542-f7l4ty2j 67 42 kbp kbp NNS cord-002542-f7l4ty2j 67 43 [ [ -LRB- cord-002542-f7l4ty2j 67 44 38 38 CD cord-002542-f7l4ty2j 67 45 ] ] -RRB- cord-002542-f7l4ty2j 67 46 ) ) -RRB- cord-002542-f7l4ty2j 67 47 sequences sequence NNS cord-002542-f7l4ty2j 67 48 of of IN cord-002542-f7l4ty2j 67 49 DNA dna NN cord-002542-f7l4ty2j 67 50 samples sample NNS cord-002542-f7l4ty2j 67 51 with with IN cord-002542-f7l4ty2j 67 52 minimal minimal JJ cord-002542-f7l4ty2j 67 53 sample sample NN cord-002542-f7l4ty2j 67 54 prep prep NN cord-002542-f7l4ty2j 67 55 . . . cord-002542-f7l4ty2j 68 1 ONT ONT NNP cord-002542-f7l4ty2j 68 2 nanopore nanopore NNP cord-002542-f7l4ty2j 68 3 sequencing sequencing NN cord-002542-f7l4ty2j 68 4 has have VBZ cord-002542-f7l4ty2j 68 5 been be VBN cord-002542-f7l4ty2j 68 6 used use VBN cord-002542-f7l4ty2j 68 7 to to TO cord-002542-f7l4ty2j 68 8 rapidly rapidly RB cord-002542-f7l4ty2j 68 9 characterize characterize VB cord-002542-f7l4ty2j 68 10 virus virus NN cord-002542-f7l4ty2j 68 11 genomes genome NNS cord-002542-f7l4ty2j 68 12 from from IN cord-002542-f7l4ty2j 68 13 metagenomic metagenomic NNP cord-002542-f7l4ty2j 68 14 samples sample NNS cord-002542-f7l4ty2j 68 15 [ [ -LRB- cord-002542-f7l4ty2j 68 16 39 39 CD cord-002542-f7l4ty2j 68 17 ] ] -RRB- cord-002542-f7l4ty2j 68 18 , , , cord-002542-f7l4ty2j 68 19 in in IN cord-002542-f7l4ty2j 68 20 the the DT cord-002542-f7l4ty2j 68 21 midst midst NN cord-002542-f7l4ty2j 68 22 of of IN cord-002542-f7l4ty2j 68 23 Ebola Ebola NNP cord-002542-f7l4ty2j 68 24 virus virus NN cord-002542-f7l4ty2j 68 25 outbreaks outbreak NNS cord-002542-f7l4ty2j 68 26 [ [ -LRB- cord-002542-f7l4ty2j 68 27 40 40 CD cord-002542-f7l4ty2j 68 28 ] ] -RRB- cord-002542-f7l4ty2j 68 29 , , , cord-002542-f7l4ty2j 68 30 and and CC cord-002542-f7l4ty2j 68 31 in in IN cord-002542-f7l4ty2j 68 32 targeted target VBN cord-002542-f7l4ty2j 68 33 studies study NNS cord-002542-f7l4ty2j 68 34 aimed aim VBN cord-002542-f7l4ty2j 68 35 at at IN cord-002542-f7l4ty2j 68 36 characterizing characterize VBG cord-002542-f7l4ty2j 68 37 sequence sequence NN cord-002542-f7l4ty2j 68 38 variations variation NNS cord-002542-f7l4ty2j 68 39 within within IN cord-002542-f7l4ty2j 68 40 influenza influenza NN cord-002542-f7l4ty2j 68 41 virus virus NN cord-002542-f7l4ty2j 68 42 samples sample NNS cord-002542-f7l4ty2j 68 43 [ [ -LRB- cord-002542-f7l4ty2j 68 44 41 41 CD cord-002542-f7l4ty2j 68 45 ] ] -RRB- cord-002542-f7l4ty2j 68 46 . . . cord-002542-f7l4ty2j 69 1 Highly highly RB cord-002542-f7l4ty2j 69 2 parallel parallel JJ cord-002542-f7l4ty2j 69 3 direct direct JJ cord-002542-f7l4ty2j 69 4 RNA rna NN cord-002542-f7l4ty2j 69 5 sequencing sequencing NN cord-002542-f7l4ty2j 69 6 using use VBG cord-002542-f7l4ty2j 69 7 Nanopore Nanopore NNP cord-002542-f7l4ty2j 69 8 technology technology NN cord-002542-f7l4ty2j 69 9 was be VBD cord-002542-f7l4ty2j 69 10 also also RB cord-002542-f7l4ty2j 69 11 recently recently RB cord-002542-f7l4ty2j 69 12 reported report VBN cord-002542-f7l4ty2j 69 13 [ [ -LRB- cord-002542-f7l4ty2j 69 14 42 42 CD cord-002542-f7l4ty2j 69 15 ] ] -RRB- cord-002542-f7l4ty2j 69 16 . . . cord-002542-f7l4ty2j 70 1 Due due IN cord-002542-f7l4ty2j 70 2 to to IN cord-002542-f7l4ty2j 70 3 the the DT cord-002542-f7l4ty2j 70 4 higher high JJR cord-002542-f7l4ty2j 70 5 error error NN cord-002542-f7l4ty2j 70 6 - - HYPH cord-002542-f7l4ty2j 70 7 rate rate NN cord-002542-f7l4ty2j 70 8 [ [ -LRB- cord-002542-f7l4ty2j 70 9 43 43 CD cord-002542-f7l4ty2j 70 10 ] ] -RRB- cord-002542-f7l4ty2j 70 11 of of IN cord-002542-f7l4ty2j 70 12 the the DT cord-002542-f7l4ty2j 70 13 nanopore nanopore NNP cord-002542-f7l4ty2j 70 14 sequencing sequencing NN cord-002542-f7l4ty2j 70 15 technology technology NN cord-002542-f7l4ty2j 70 16 compared compare VBN cord-002542-f7l4ty2j 70 17 to to IN cord-002542-f7l4ty2j 70 18 other other JJ cord-002542-f7l4ty2j 70 19 RNAseq RNAseq NNP cord-002542-f7l4ty2j 70 20 platforms platform NNS cord-002542-f7l4ty2j 70 21 , , , cord-002542-f7l4ty2j 70 22 the the DT cord-002542-f7l4ty2j 70 23 exact exact JJ cord-002542-f7l4ty2j 70 24 identity identity NN cord-002542-f7l4ty2j 70 25 of of IN cord-002542-f7l4ty2j 70 26 recombination recombination NN cord-002542-f7l4ty2j 70 27 events event NNS cord-002542-f7l4ty2j 70 28 within within IN cord-002542-f7l4ty2j 70 29 singlemolecule singlemolecule JJ cord-002542-f7l4ty2j 70 30 genomes genome NNS cord-002542-f7l4ty2j 70 31 may may MD cord-002542-f7l4ty2j 70 32 be be VB cord-002542-f7l4ty2j 70 33 inaccurate inaccurate JJ cord-002542-f7l4ty2j 70 34 . . . cord-002542-f7l4ty2j 71 1 However however RB cord-002542-f7l4ty2j 71 2 , , , cord-002542-f7l4ty2j 71 3 long long RB cord-002542-f7l4ty2j 71 4 - - HYPH cord-002542-f7l4ty2j 71 5 read read VBN cord-002542-f7l4ty2j 71 6 nanopore nanopore NNP cord-002542-f7l4ty2j 71 7 reads read VBZ cord-002542-f7l4ty2j 71 8 provide provide VB cord-002542-f7l4ty2j 71 9 the the DT cord-002542-f7l4ty2j 71 10 distinct distinct JJ cord-002542-f7l4ty2j 71 11 advantage advantage NN cord-002542-f7l4ty2j 71 12 of of IN cord-002542-f7l4ty2j 71 13 being be VBG cord-002542-f7l4ty2j 71 14 able able JJ cord-002542-f7l4ty2j 71 15 to to TO cord-002542-f7l4ty2j 71 16 sequence sequence VB cord-002542-f7l4ty2j 71 17 full full JJ cord-002542-f7l4ty2j 71 18 - - HYPH cord-002542-f7l4ty2j 71 19 length length NN cord-002542-f7l4ty2j 71 20 cDNA cdna NN cord-002542-f7l4ty2j 71 21 copies copy NNS cord-002542-f7l4ty2j 71 22 of of IN cord-002542-f7l4ty2j 71 23 RNA RNA NNP cord-002542-f7l4ty2j 71 24 virus virus NN cord-002542-f7l4ty2j 71 25 genomes genome NNS cord-002542-f7l4ty2j 71 26 and and CC cord-002542-f7l4ty2j 71 27 thus thus RB cord-002542-f7l4ty2j 71 28 can can MD cord-002542-f7l4ty2j 71 29 resolve resolve VB cord-002542-f7l4ty2j 71 30 multiple multiple JJ cord-002542-f7l4ty2j 71 31 recombination recombination NN cord-002542-f7l4ty2j 71 32 events event NNS cord-002542-f7l4ty2j 71 33 within within IN cord-002542-f7l4ty2j 71 34 a a DT cord-002542-f7l4ty2j 71 35 single single JJ cord-002542-f7l4ty2j 71 36 RNA RNA NNP cord-002542-f7l4ty2j 71 37 virus virus NN cord-002542-f7l4ty2j 71 38 genome genome NN cord-002542-f7l4ty2j 71 39 . . . cord-002542-f7l4ty2j 72 1 This this DT cord-002542-f7l4ty2j 72 2 study study NN cord-002542-f7l4ty2j 72 3 provides provide VBZ cord-002542-f7l4ty2j 72 4 a a DT cord-002542-f7l4ty2j 72 5 comprehensive comprehensive JJ cord-002542-f7l4ty2j 72 6 analysis analysis NN cord-002542-f7l4ty2j 72 7 of of IN cord-002542-f7l4ty2j 72 8 the the DT cord-002542-f7l4ty2j 72 9 steps step NNS cord-002542-f7l4ty2j 72 10 and and CC cord-002542-f7l4ty2j 72 11 pathways pathway NNS cord-002542-f7l4ty2j 72 12 governing govern VBG cord-002542-f7l4ty2j 72 13 DI DI NNP cord-002542-f7l4ty2j 72 14 - - HYPH cord-002542-f7l4ty2j 72 15 RNA RNA NNP cord-002542-f7l4ty2j 72 16 emergence emergence NN cord-002542-f7l4ty2j 72 17 and and CC cord-002542-f7l4ty2j 72 18 evolution evolution NN cord-002542-f7l4ty2j 72 19 starting start VBG cord-002542-f7l4ty2j 72 20 from from IN cord-002542-f7l4ty2j 72 21 a a DT cord-002542-f7l4ty2j 72 22 plasmid plasmid NN cord-002542-f7l4ty2j 72 23 - - HYPH cord-002542-f7l4ty2j 72 24 driven drive VBN cord-002542-f7l4ty2j 72 25 inoculum inoculum NN cord-002542-f7l4ty2j 72 26 through through IN cord-002542-f7l4ty2j 72 27 to to IN cord-002542-f7l4ty2j 72 28 a a DT cord-002542-f7l4ty2j 72 29 highly highly RB cord-002542-f7l4ty2j 72 30 - - HYPH cord-002542-f7l4ty2j 72 31 passaged passage VBN cord-002542-f7l4ty2j 72 32 sample sample NN cord-002542-f7l4ty2j 72 33 . . . cord-002542-f7l4ty2j 73 1 By by IN cord-002542-f7l4ty2j 73 2 combining combine VBG cord-002542-f7l4ty2j 73 3 short short JJ cord-002542-f7l4ty2j 73 4 - - HYPH cord-002542-f7l4ty2j 73 5 read read VBN cord-002542-f7l4ty2j 73 6 and and CC cord-002542-f7l4ty2j 73 7 long long RB cord-002542-f7l4ty2j 73 8 - - HYPH cord-002542-f7l4ty2j 73 9 read read VBN cord-002542-f7l4ty2j 73 10 sequencing sequencing NN cord-002542-f7l4ty2j 73 11 technologies technology NNS cord-002542-f7l4ty2j 73 12 , , , cord-002542-f7l4ty2j 73 13 we -PRON- PRP cord-002542-f7l4ty2j 73 14 determine determine VBP cord-002542-f7l4ty2j 73 15 both both CC cord-002542-f7l4ty2j 73 16 the the DT cord-002542-f7l4ty2j 73 17 exact exact JJ cord-002542-f7l4ty2j 73 18 identity identity NN cord-002542-f7l4ty2j 73 19 of of IN cord-002542-f7l4ty2j 73 20 RNA RNA NNP cord-002542-f7l4ty2j 73 21 recombination recombination NN cord-002542-f7l4ty2j 73 22 sites site NNS cord-002542-f7l4ty2j 73 23 and and CC cord-002542-f7l4ty2j 73 24 their -PRON- PRP$ cord-002542-f7l4ty2j 73 25 correlation correlation NN cord-002542-f7l4ty2j 73 26 within within IN cord-002542-f7l4ty2j 73 27 the the DT cord-002542-f7l4ty2j 73 28 viral viral JJ cord-002542-f7l4ty2j 73 29 quasispecies quasispecie NNS cord-002542-f7l4ty2j 73 30 . . . cord-002542-f7l4ty2j 74 1 We -PRON- PRP cord-002542-f7l4ty2j 74 2 find find VBP cord-002542-f7l4ty2j 74 3 little little JJ cord-002542-f7l4ty2j 74 4 evidence evidence NN cord-002542-f7l4ty2j 74 5 for for IN cord-002542-f7l4ty2j 74 6 the the DT cord-002542-f7l4ty2j 74 7 accumulation accumulation NN cord-002542-f7l4ty2j 74 8 of of IN cord-002542-f7l4ty2j 74 9 intermediate intermediate JJ cord-002542-f7l4ty2j 74 10 defective defective JJ cord-002542-f7l4ty2j 74 11 RNA RNA NNP cord-002542-f7l4ty2j 74 12 species specie NNS cord-002542-f7l4ty2j 74 13 that that WDT cord-002542-f7l4ty2j 74 14 contain contain VBP cord-002542-f7l4ty2j 74 15 either either CC cord-002542-f7l4ty2j 74 16 only only RB cord-002542-f7l4ty2j 74 17 one one CD cord-002542-f7l4ty2j 74 18 , , , cord-002542-f7l4ty2j 74 19 or or CC cord-002542-f7l4ty2j 74 20 smaller small JJR cord-002542-f7l4ty2j 74 21 , , , cord-002542-f7l4ty2j 74 22 deletions deletion NNS cord-002542-f7l4ty2j 74 23 during during IN cord-002542-f7l4ty2j 74 24 the the DT cord-002542-f7l4ty2j 74 25 course course NN cord-002542-f7l4ty2j 74 26 of of IN cord-002542-f7l4ty2j 74 27 passaging passaging NN cord-002542-f7l4ty2j 74 28 . . . cord-002542-f7l4ty2j 75 1 Rather rather RB cord-002542-f7l4ty2j 75 2 , , , cord-002542-f7l4ty2j 75 3 fully fully RB cord-002542-f7l4ty2j 75 4 formed form VBD cord-002542-f7l4ty2j 75 5 ' ' `` cord-002542-f7l4ty2j 75 6 mature mature VB cord-002542-f7l4ty2j 75 7 ' ' '' cord-002542-f7l4ty2j 75 8 DI di NN cord-002542-f7l4ty2j 75 9 - - HYPH cord-002542-f7l4ty2j 75 10 RNAs rna NNS cord-002542-f7l4ty2j 75 11 that that WDT cord-002542-f7l4ty2j 75 12 are be VBP cord-002542-f7l4ty2j 75 13 characterized characterize VBN cord-002542-f7l4ty2j 75 14 by by IN cord-002542-f7l4ty2j 75 15 two two CD cord-002542-f7l4ty2j 75 16 to to TO cord-002542-f7l4ty2j 75 17 three three CD cord-002542-f7l4ty2j 75 18 deletions deletion NNS cord-002542-f7l4ty2j 75 19 between between IN cord-002542-f7l4ty2j 75 20 a a DT cord-002542-f7l4ty2j 75 21 limited limited JJ cord-002542-f7l4ty2j 75 22 number number NN cord-002542-f7l4ty2j 75 23 of of IN cord-002542-f7l4ty2j 75 24 positions position NNS cord-002542-f7l4ty2j 75 25 in in IN cord-002542-f7l4ty2j 75 26 each each DT cord-002542-f7l4ty2j 75 27 of of IN cord-002542-f7l4ty2j 75 28 the the DT cord-002542-f7l4ty2j 75 29 FHV FHV NNP cord-002542-f7l4ty2j 75 30 genomic genomic JJ cord-002542-f7l4ty2j 75 31 RNAs rna NNS cord-002542-f7l4ty2j 76 1 appear appear VB cord-002542-f7l4ty2j 76 2 after after IN cord-002542-f7l4ty2j 76 3 approximately approximately RB cord-002542-f7l4ty2j 76 4 9 9 CD cord-002542-f7l4ty2j 76 5 days day NNS cord-002542-f7l4ty2j 76 6 of of IN cord-002542-f7l4ty2j 76 7 viral viral JJ cord-002542-f7l4ty2j 76 8 passaging passaging NN cord-002542-f7l4ty2j 76 9 and and CC cord-002542-f7l4ty2j 76 10 accumulate accumulate VBP cord-002542-f7l4ty2j 76 11 rapidly rapidly RB cord-002542-f7l4ty2j 76 12 . . . cord-002542-f7l4ty2j 77 1 The the DT cord-002542-f7l4ty2j 77 2 accumulation accumulation NN cord-002542-f7l4ty2j 77 3 of of IN cord-002542-f7l4ty2j 77 4 DI DI NNP cord-002542-f7l4ty2j 77 5 - - HYPH cord-002542-f7l4ty2j 77 6 RNAs rna NNS cord-002542-f7l4ty2j 77 7 corresponds correspond VBZ cord-002542-f7l4ty2j 77 8 with with IN cord-002542-f7l4ty2j 77 9 a a DT cord-002542-f7l4ty2j 77 10 reduction reduction NN cord-002542-f7l4ty2j 77 11 in in IN cord-002542-f7l4ty2j 77 12 the the DT cord-002542-f7l4ty2j 77 13 specific specific JJ cord-002542-f7l4ty2j 77 14 infectivity infectivity NN cord-002542-f7l4ty2j 77 15 of of IN cord-002542-f7l4ty2j 77 16 the the DT cord-002542-f7l4ty2j 77 17 viral viral JJ cord-002542-f7l4ty2j 77 18 samples sample NNS cord-002542-f7l4ty2j 77 19 in in IN cord-002542-f7l4ty2j 77 20 each each DT cord-002542-f7l4ty2j 77 21 passage passage NN cord-002542-f7l4ty2j 77 22 . . . cord-002542-f7l4ty2j 78 1 This this DT cord-002542-f7l4ty2j 78 2 implies imply VBZ cord-002542-f7l4ty2j 78 3 that that IN cord-002542-f7l4ty2j 78 4 partially partially RB cord-002542-f7l4ty2j 78 5 formed form VBN cord-002542-f7l4ty2j 78 6 DI DI NNP cord-002542-f7l4ty2j 78 7 - - HYPH cord-002542-f7l4ty2j 78 8 RNA RNA NNP cord-002542-f7l4ty2j 78 9 species specie NNS cord-002542-f7l4ty2j 78 10 are be VBP cord-002542-f7l4ty2j 78 11 not not RB cord-002542-f7l4ty2j 78 12 competitive competitive JJ cord-002542-f7l4ty2j 78 13 and and CC cord-002542-f7l4ty2j 78 14 can can MD cord-002542-f7l4ty2j 78 15 not not RB cord-002542-f7l4ty2j 78 16 accumulate accumulate VB cord-002542-f7l4ty2j 78 17 in in IN cord-002542-f7l4ty2j 78 18 the the DT cord-002542-f7l4ty2j 78 19 manner manner NN cord-002542-f7l4ty2j 78 20 that that WDT cord-002542-f7l4ty2j 78 21 mature mature VBP cord-002542-f7l4ty2j 78 22 DI DI NNP cord-002542-f7l4ty2j 78 23 - - HYPH cord-002542-f7l4ty2j 78 24 RNA RNA NNP cord-002542-f7l4ty2j 78 25 species specie NNS cord-002542-f7l4ty2j 78 26 do do VBP cord-002542-f7l4ty2j 78 27 , , , cord-002542-f7l4ty2j 78 28 perhaps perhaps RB cord-002542-f7l4ty2j 78 29 due due IN cord-002542-f7l4ty2j 78 30 to to IN cord-002542-f7l4ty2j 78 31 the the DT cord-002542-f7l4ty2j 78 32 epistatic epistatic JJ cord-002542-f7l4ty2j 78 33 interaction interaction NN cord-002542-f7l4ty2j 78 34 of of IN cord-002542-f7l4ty2j 78 35 multiple multiple JJ cord-002542-f7l4ty2j 78 36 recombination recombination NN cord-002542-f7l4ty2j 78 37 events event NNS cord-002542-f7l4ty2j 78 38 . . . cord-002542-f7l4ty2j 79 1 Alternatively alternatively RB cord-002542-f7l4ty2j 79 2 , , , cord-002542-f7l4ty2j 79 3 the the DT cord-002542-f7l4ty2j 79 4 formation formation NN cord-002542-f7l4ty2j 79 5 of of IN cord-002542-f7l4ty2j 79 6 mature mature JJ cord-002542-f7l4ty2j 79 7 DI DI NNP cord-002542-f7l4ty2j 79 8 - - HYPH cord-002542-f7l4ty2j 79 9 RNAs rna NNS cord-002542-f7l4ty2j 79 10 may may MD cord-002542-f7l4ty2j 79 11 occur occur VB cord-002542-f7l4ty2j 79 12 in in IN cord-002542-f7l4ty2j 79 13 a a DT cord-002542-f7l4ty2j 79 14 single single JJ cord-002542-f7l4ty2j 79 15 step step NN cord-002542-f7l4ty2j 79 16 involving involve VBG cord-002542-f7l4ty2j 79 17 multiple multiple JJ cord-002542-f7l4ty2j 79 18 simultaneous simultaneous JJ cord-002542-f7l4ty2j 79 19 genome genome NN cord-002542-f7l4ty2j 79 20 rearrangements rearrangement NNS cord-002542-f7l4ty2j 79 21 . . . cord-002542-f7l4ty2j 80 1 Cell cell NN cord-002542-f7l4ty2j 80 2 culture culture NN cord-002542-f7l4ty2j 80 3 and and CC cord-002542-f7l4ty2j 80 4 virus virus NN cord-002542-f7l4ty2j 80 5 passaging passage VBG cord-002542-f7l4ty2j 80 6 D. D. NNP cord-002542-f7l4ty2j 80 7 melanogaster melanogaster NN cord-002542-f7l4ty2j 80 8 ( ( -LRB- cord-002542-f7l4ty2j 80 9 S2 S2 NNP cord-002542-f7l4ty2j 80 10 ) ) -RRB- cord-002542-f7l4ty2j 80 11 cells cell NNS cord-002542-f7l4ty2j 80 12 were be VBD cord-002542-f7l4ty2j 80 13 grown grow VBN cord-002542-f7l4ty2j 80 14 at at IN cord-002542-f7l4ty2j 80 15 28˚C 28˚c CD cord-002542-f7l4ty2j 80 16 in in IN cord-002542-f7l4ty2j 80 17 Schneider Schneider NNP cord-002542-f7l4ty2j 80 18 's 's POS cord-002542-f7l4ty2j 80 19 Drosophila Drosophila NNP cord-002542-f7l4ty2j 80 20 Media medium NNS cord-002542-f7l4ty2j 80 21 supplemented supplement VBD cord-002542-f7l4ty2j 80 22 with with IN cord-002542-f7l4ty2j 80 23 10 10 CD cord-002542-f7l4ty2j 80 24 % % NN cord-002542-f7l4ty2j 80 25 fetal fetal JJ cord-002542-f7l4ty2j 80 26 bovine bovine JJ cord-002542-f7l4ty2j 80 27 serum serum NN cord-002542-f7l4ty2j 80 28 and and CC cord-002542-f7l4ty2j 80 29 1X 1x JJ cord-002542-f7l4ty2j 80 30 Penicillin Penicillin NNP cord-002542-f7l4ty2j 80 31 - - HYPH cord-002542-f7l4ty2j 80 32 Streptomycin Streptomycin NNP cord-002542-f7l4ty2j 80 33 using use VBG cord-002542-f7l4ty2j 80 34 standard standard JJ cord-002542-f7l4ty2j 80 35 laboratory laboratory NN cord-002542-f7l4ty2j 80 36 procedures procedure NNS cord-002542-f7l4ty2j 80 37 . . . cord-002542-f7l4ty2j 81 1 To to TO cord-002542-f7l4ty2j 81 2 generate generate VB cord-002542-f7l4ty2j 81 3 the the DT cord-002542-f7l4ty2j 81 4 initial initial JJ cord-002542-f7l4ty2j 81 5 Flock Flock NNP cord-002542-f7l4ty2j 81 6 House House NNP cord-002542-f7l4ty2j 81 7 virus virus NN cord-002542-f7l4ty2j 81 8 inoculum inoculum NN cord-002542-f7l4ty2j 81 9 , , , cord-002542-f7l4ty2j 81 10 S2 s2 NN cord-002542-f7l4ty2j 81 11 cells cell NNS cord-002542-f7l4ty2j 81 12 were be VBD cord-002542-f7l4ty2j 81 13 plated plate VBN cord-002542-f7l4ty2j 81 14 at at IN cord-002542-f7l4ty2j 81 15 50 50 CD cord-002542-f7l4ty2j 81 16 - - SYM cord-002542-f7l4ty2j 81 17 70 70 CD cord-002542-f7l4ty2j 81 18 % % NN cord-002542-f7l4ty2j 81 19 confluency confluency NN cord-002542-f7l4ty2j 81 20 in in IN cord-002542-f7l4ty2j 81 21 a a DT cord-002542-f7l4ty2j 81 22 six six CD cord-002542-f7l4ty2j 81 23 well well JJ cord-002542-f7l4ty2j 81 24 plate plate NN cord-002542-f7l4ty2j 81 25 and and CC cord-002542-f7l4ty2j 81 26 were be VBD cord-002542-f7l4ty2j 81 27 transfected transfecte VBN cord-002542-f7l4ty2j 81 28 with with IN cord-002542-f7l4ty2j 81 29 2.5μg 2.5μg CD cord-002542-f7l4ty2j 81 30 of of IN cord-002542-f7l4ty2j 81 31 pMT pMT NNP cord-002542-f7l4ty2j 81 32 plasmid plasmid NN cord-002542-f7l4ty2j 81 33 containing contain VBG cord-002542-f7l4ty2j 81 34 FHV FHV NNP cord-002542-f7l4ty2j 81 35 RNA1 RNA1 NNP cord-002542-f7l4ty2j 81 36 ( ( -LRB- cord-002542-f7l4ty2j 81 37 NC_004146 NC_004146 NNP cord-002542-f7l4ty2j 81 38 ) ) -RRB- cord-002542-f7l4ty2j 81 39 and and CC cord-002542-f7l4ty2j 81 40 2.5μg 2.5μg CD cord-002542-f7l4ty2j 81 41 of of IN cord-002542-f7l4ty2j 81 42 pMT pMT NNP cord-002542-f7l4ty2j 81 43 plasmid plasmid NN cord-002542-f7l4ty2j 81 44 containing contain VBG cord-002542-f7l4ty2j 81 45 FHV FHV NNP cord-002542-f7l4ty2j 81 46 RNA2 RNA2 NNP cord-002542-f7l4ty2j 81 47 ( ( -LRB- cord-002542-f7l4ty2j 81 48 NC_004144 nc_004144 NN cord-002542-f7l4ty2j 81 49 ) ) -RRB- cord-002542-f7l4ty2j 81 50 using use VBG cord-002542-f7l4ty2j 81 51 Lipofectamine Lipofectamine NNP cord-002542-f7l4ty2j 81 52 3000 3000 CD cord-002542-f7l4ty2j 81 53 Transfection Transfection NNP cord-002542-f7l4ty2j 81 54 Reagent Reagent NNP cord-002542-f7l4ty2j 81 55 as as IN cord-002542-f7l4ty2j 81 56 per per IN cord-002542-f7l4ty2j 81 57 the the DT cord-002542-f7l4ty2j 81 58 manufacturer manufacturer NN cord-002542-f7l4ty2j 81 59 's 's POS cord-002542-f7l4ty2j 81 60 protocol protocol NN cord-002542-f7l4ty2j 81 61 . . . cord-002542-f7l4ty2j 82 1 Plasmid plasmid NN cord-002542-f7l4ty2j 82 2 transcription transcription NN cord-002542-f7l4ty2j 82 3 was be VBD cord-002542-f7l4ty2j 82 4 induced induce VBN cord-002542-f7l4ty2j 82 5 24 24 CD cord-002542-f7l4ty2j 82 6 hours hour NNS cord-002542-f7l4ty2j 82 7 post post NN cord-002542-f7l4ty2j 82 8 transfection transfection NN cord-002542-f7l4ty2j 82 9 with with IN cord-002542-f7l4ty2j 82 10 the the DT cord-002542-f7l4ty2j 82 11 addition addition NN cord-002542-f7l4ty2j 82 12 of of IN cord-002542-f7l4ty2j 82 13 50mM 50mm CD cord-002542-f7l4ty2j 82 14 CuSO CuSO NNP cord-002542-f7l4ty2j 82 15 4 4 CD cord-002542-f7l4ty2j 82 16 . . . cord-002542-f7l4ty2j 83 1 Virus virus NN cord-002542-f7l4ty2j 83 2 was be VBD cord-002542-f7l4ty2j 83 3 then then RB cord-002542-f7l4ty2j 83 4 allowed allow VBN cord-002542-f7l4ty2j 83 5 to to TO cord-002542-f7l4ty2j 83 6 propagate propagate VB cord-002542-f7l4ty2j 83 7 for for IN cord-002542-f7l4ty2j 83 8 3 3 CD cord-002542-f7l4ty2j 83 9 days day NNS cord-002542-f7l4ty2j 83 10 post post NN cord-002542-f7l4ty2j 83 11 induction induction NN cord-002542-f7l4ty2j 83 12 . . . cord-002542-f7l4ty2j 84 1 For for IN cord-002542-f7l4ty2j 84 2 successive successive JJ cord-002542-f7l4ty2j 84 3 passages passage NNS cord-002542-f7l4ty2j 84 4 ( ( -LRB- cord-002542-f7l4ty2j 84 5 Passages Passages NNP cord-002542-f7l4ty2j 84 6 1 1 CD cord-002542-f7l4ty2j 84 7 - - SYM cord-002542-f7l4ty2j 84 8 9 9 CD cord-002542-f7l4ty2j 84 9 ) ) -RRB- cord-002542-f7l4ty2j 84 10 , , , cord-002542-f7l4ty2j 84 11 S2 s2 NN cord-002542-f7l4ty2j 84 12 cells cell NNS cord-002542-f7l4ty2j 84 13 were be VBD cord-002542-f7l4ty2j 84 14 grown grow VBN cord-002542-f7l4ty2j 84 15 in in IN cord-002542-f7l4ty2j 84 16 T-25 T-25 NNP cord-002542-f7l4ty2j 84 17 flasks flask NNS cord-002542-f7l4ty2j 84 18 to to IN cord-002542-f7l4ty2j 84 19 70 70 CD cord-002542-f7l4ty2j 84 20 - - SYM cord-002542-f7l4ty2j 84 21 90 90 CD cord-002542-f7l4ty2j 84 22 % % NN cord-002542-f7l4ty2j 84 23 confluency confluency NN cord-002542-f7l4ty2j 85 1 ( ( -LRB- cord-002542-f7l4ty2j 85 2 ~1 ~1 NNP cord-002542-f7l4ty2j 85 3 x x SYM cord-002542-f7l4ty2j 85 4 10 10 CD cord-002542-f7l4ty2j 85 5 7 7 CD cord-002542-f7l4ty2j 85 6 cells cell NNS cord-002542-f7l4ty2j 85 7 ) ) -RRB- cord-002542-f7l4ty2j 85 8 , , , cord-002542-f7l4ty2j 85 9 then then RB cord-002542-f7l4ty2j 85 10 infected infect VBN cord-002542-f7l4ty2j 85 11 with with IN cord-002542-f7l4ty2j 85 12 1mL 1ml CD cord-002542-f7l4ty2j 85 13 of of IN cord-002542-f7l4ty2j 85 14 viral viral JJ cord-002542-f7l4ty2j 85 15 inoculum inoculum NN cord-002542-f7l4ty2j 85 16 from from IN cord-002542-f7l4ty2j 85 17 the the DT cord-002542-f7l4ty2j 85 18 previous previous JJ cord-002542-f7l4ty2j 85 19 passage passage NN cord-002542-f7l4ty2j 85 20 . . . cord-002542-f7l4ty2j 86 1 Virus virus NN cord-002542-f7l4ty2j 86 2 was be VBD cord-002542-f7l4ty2j 86 3 grown grow VBN cord-002542-f7l4ty2j 86 4 for for IN cord-002542-f7l4ty2j 86 5 3 3 CD cord-002542-f7l4ty2j 86 6 days day NNS cord-002542-f7l4ty2j 86 7 , , , cord-002542-f7l4ty2j 86 8 then then RB cord-002542-f7l4ty2j 86 9 fractions fraction NNS cord-002542-f7l4ty2j 86 10 were be VBD cord-002542-f7l4ty2j 86 11 harvested harvest VBN cord-002542-f7l4ty2j 86 12 for for IN cord-002542-f7l4ty2j 86 13 viral viral JJ cord-002542-f7l4ty2j 86 14 purification purification NN cord-002542-f7l4ty2j 86 15 or or CC cord-002542-f7l4ty2j 86 16 inoculation inoculation NN cord-002542-f7l4ty2j 86 17 of of IN cord-002542-f7l4ty2j 86 18 the the DT cord-002542-f7l4ty2j 86 19 next next JJ cord-002542-f7l4ty2j 86 20 passage passage NN cord-002542-f7l4ty2j 86 21 . . . cord-002542-f7l4ty2j 87 1 To to TO cord-002542-f7l4ty2j 87 2 purify purify VB cord-002542-f7l4ty2j 87 3 virus virus NN cord-002542-f7l4ty2j 87 4 from from IN cord-002542-f7l4ty2j 87 5 each each DT cord-002542-f7l4ty2j 87 6 consecutive consecutive JJ cord-002542-f7l4ty2j 87 7 serial serial JJ cord-002542-f7l4ty2j 87 8 passage passage NN cord-002542-f7l4ty2j 87 9 , , , cord-002542-f7l4ty2j 87 10 cells cell NNS cord-002542-f7l4ty2j 87 11 and and CC cord-002542-f7l4ty2j 87 12 supernatant supernatant JJ cord-002542-f7l4ty2j 87 13 were be VBD cord-002542-f7l4ty2j 87 14 subjected subject VBN cord-002542-f7l4ty2j 87 15 to to IN cord-002542-f7l4ty2j 87 16 a a DT cord-002542-f7l4ty2j 87 17 freeze freeze NN cord-002542-f7l4ty2j 87 18 - - HYPH cord-002542-f7l4ty2j 87 19 thaw thaw NN cord-002542-f7l4ty2j 87 20 cycle cycle NN cord-002542-f7l4ty2j 87 21 in in IN cord-002542-f7l4ty2j 87 22 the the DT cord-002542-f7l4ty2j 87 23 presence presence NN cord-002542-f7l4ty2j 87 24 of of IN cord-002542-f7l4ty2j 87 25 1 1 CD cord-002542-f7l4ty2j 87 26 % % NN cord-002542-f7l4ty2j 87 27 Triton Triton NNP cord-002542-f7l4ty2j 87 28 X-100 x-100 NN cord-002542-f7l4ty2j 87 29 to to TO cord-002542-f7l4ty2j 87 30 release release VB cord-002542-f7l4ty2j 87 31 viral viral JJ cord-002542-f7l4ty2j 87 32 particles particle NNS cord-002542-f7l4ty2j 87 33 from from IN cord-002542-f7l4ty2j 87 34 infected infected JJ cord-002542-f7l4ty2j 87 35 cells cell NNS cord-002542-f7l4ty2j 87 36 . . . cord-002542-f7l4ty2j 88 1 Virus virus NN cord-002542-f7l4ty2j 88 2 particles particle NNS cord-002542-f7l4ty2j 88 3 were be VBD cord-002542-f7l4ty2j 88 4 then then RB cord-002542-f7l4ty2j 88 5 purified purify VBN cord-002542-f7l4ty2j 88 6 on on IN cord-002542-f7l4ty2j 88 7 a a DT cord-002542-f7l4ty2j 88 8 30 30 CD cord-002542-f7l4ty2j 88 9 % % NN cord-002542-f7l4ty2j 88 10 sucrose sucrose NN cord-002542-f7l4ty2j 88 11 cushion cushion NN cord-002542-f7l4ty2j 88 12 by by IN cord-002542-f7l4ty2j 88 13 spinning spin VBG cord-002542-f7l4ty2j 88 14 the the DT cord-002542-f7l4ty2j 88 15 cell cell NN cord-002542-f7l4ty2j 88 16 lysate lysate NN cord-002542-f7l4ty2j 88 17 at at IN cord-002542-f7l4ty2j 88 18 40,000 40,000 CD cord-002542-f7l4ty2j 88 19 RPM rpm NN cord-002542-f7l4ty2j 88 20 for for IN cord-002542-f7l4ty2j 88 21 2.5 2.5 CD cord-002542-f7l4ty2j 88 22 hours hour NNS cord-002542-f7l4ty2j 88 23 . . . cord-002542-f7l4ty2j 89 1 The the DT cord-002542-f7l4ty2j 89 2 viral viral JJ cord-002542-f7l4ty2j 89 3 pellet pellet NN cord-002542-f7l4ty2j 89 4 was be VBD cord-002542-f7l4ty2j 89 5 resuspended resuspend VBN cord-002542-f7l4ty2j 89 6 in in IN cord-002542-f7l4ty2j 89 7 10mM 10mm CD cord-002542-f7l4ty2j 89 8 Tris Tris NNP cord-002542-f7l4ty2j 89 9 ( ( -LRB- cord-002542-f7l4ty2j 89 10 pH pH NNP cord-002542-f7l4ty2j 89 11 7.4 7.4 CD cord-002542-f7l4ty2j 89 12 ) ) -RRB- cord-002542-f7l4ty2j 89 13 . . . cord-002542-f7l4ty2j 90 1 Virus virus NN cord-002542-f7l4ty2j 90 2 was be VBD cord-002542-f7l4ty2j 90 3 further further RB cord-002542-f7l4ty2j 90 4 purified purify VBN cord-002542-f7l4ty2j 90 5 by by IN cord-002542-f7l4ty2j 90 6 applying apply VBG cord-002542-f7l4ty2j 90 7 resuspended resuspended JJ cord-002542-f7l4ty2j 90 8 virus virus NN cord-002542-f7l4ty2j 90 9 atop atop IN cord-002542-f7l4ty2j 90 10 a a DT cord-002542-f7l4ty2j 90 11 10 10 CD cord-002542-f7l4ty2j 90 12 - - SYM cord-002542-f7l4ty2j 90 13 40 40 CD cord-002542-f7l4ty2j 90 14 % % NN cord-002542-f7l4ty2j 90 15 sucrose sucrose NN cord-002542-f7l4ty2j 90 16 gradient gradient NN cord-002542-f7l4ty2j 90 17 and and CC cord-002542-f7l4ty2j 90 18 spun spin VBD cord-002542-f7l4ty2j 90 19 at at IN cord-002542-f7l4ty2j 90 20 40,000 40,000 CD cord-002542-f7l4ty2j 90 21 RPM rpm NN cord-002542-f7l4ty2j 90 22 for for IN cord-002542-f7l4ty2j 90 23 1.5 1.5 CD cord-002542-f7l4ty2j 90 24 hours hour NNS cord-002542-f7l4ty2j 90 25 . . . cord-002542-f7l4ty2j 91 1 The the DT cord-002542-f7l4ty2j 91 2 viral viral JJ cord-002542-f7l4ty2j 91 3 band band NN cord-002542-f7l4ty2j 91 4 was be VBD cord-002542-f7l4ty2j 91 5 collected collect VBN cord-002542-f7l4ty2j 91 6 and and CC cord-002542-f7l4ty2j 91 7 subsequently subsequently RB cord-002542-f7l4ty2j 91 8 treated treat VBN cord-002542-f7l4ty2j 91 9 with with IN cord-002542-f7l4ty2j 91 10 1 1 CD cord-002542-f7l4ty2j 91 11 Unit Unit NNP cord-002542-f7l4ty2j 91 12 DNase DNase NNP cord-002542-f7l4ty2j 91 13 and and CC cord-002542-f7l4ty2j 91 14 1 1 CD cord-002542-f7l4ty2j 91 15 Unit unit NN cord-002542-f7l4ty2j 91 16 RNase rnase NN cord-002542-f7l4ty2j 91 17 and and CC cord-002542-f7l4ty2j 91 18 incubated incubate VBN cord-002542-f7l4ty2j 91 19 at at IN cord-002542-f7l4ty2j 91 20 room room NN cord-002542-f7l4ty2j 91 21 temperature temperature NN cord-002542-f7l4ty2j 91 22 for for IN cord-002542-f7l4ty2j 91 23 at at RB cord-002542-f7l4ty2j 91 24 least least RBS cord-002542-f7l4ty2j 91 25 one one CD cord-002542-f7l4ty2j 91 26 hour hour NN cord-002542-f7l4ty2j 91 27 to to TO cord-002542-f7l4ty2j 91 28 remove remove VB cord-002542-f7l4ty2j 91 29 any any DT cord-002542-f7l4ty2j 91 30 cellular cellular JJ cord-002542-f7l4ty2j 91 31 nucleic nucleic JJ cord-002542-f7l4ty2j 91 32 acids acid NNS cord-002542-f7l4ty2j 91 33 not not RB cord-002542-f7l4ty2j 91 34 protected protect VBN cord-002542-f7l4ty2j 91 35 by by IN cord-002542-f7l4ty2j 91 36 the the DT cord-002542-f7l4ty2j 91 37 viral viral JJ cord-002542-f7l4ty2j 91 38 capsid capsid NN cord-002542-f7l4ty2j 91 39 . . . cord-002542-f7l4ty2j 92 1 The the DT cord-002542-f7l4ty2j 92 2 virus virus NN cord-002542-f7l4ty2j 92 3 sample sample NN cord-002542-f7l4ty2j 92 4 was be VBD cord-002542-f7l4ty2j 92 5 concentrated concentrate VBN cord-002542-f7l4ty2j 92 6 on on IN cord-002542-f7l4ty2j 92 7 a a DT cord-002542-f7l4ty2j 92 8 100,000 100,000 CD cord-002542-f7l4ty2j 92 9 NMWL NMWL NNP cord-002542-f7l4ty2j 92 10 centrifugal centrifugal JJ cord-002542-f7l4ty2j 92 11 filter filter NN cord-002542-f7l4ty2j 92 12 column column NN cord-002542-f7l4ty2j 92 13 and and CC cord-002542-f7l4ty2j 92 14 washed wash VBD cord-002542-f7l4ty2j 92 15 with with IN cord-002542-f7l4ty2j 92 16 at at RB cord-002542-f7l4ty2j 92 17 least least JJS cord-002542-f7l4ty2j 92 18 2 2 CD cord-002542-f7l4ty2j 92 19 volumes volume NNS cord-002542-f7l4ty2j 92 20 of of IN cord-002542-f7l4ty2j 92 21 10mM 10mm CD cord-002542-f7l4ty2j 92 22 Tris Tris NNP cord-002542-f7l4ty2j 92 23 pH pH NNP cord-002542-f7l4ty2j 92 24 7.4 7.4 CD cord-002542-f7l4ty2j 92 25 . . . cord-002542-f7l4ty2j 93 1 Finally finally RB cord-002542-f7l4ty2j 93 2 , , , cord-002542-f7l4ty2j 93 3 encapsidated encapsidate VBN cord-002542-f7l4ty2j 93 4 viral viral NNP cord-002542-f7l4ty2j 93 5 RNA RNA NNP cord-002542-f7l4ty2j 93 6 was be VBD cord-002542-f7l4ty2j 93 7 extracted extract VBN cord-002542-f7l4ty2j 93 8 using use VBG cord-002542-f7l4ty2j 93 9 a a DT cord-002542-f7l4ty2j 93 10 QIAGEN QIAGEN NNP cord-002542-f7l4ty2j 93 11 RNeasy RNeasy NNP cord-002542-f7l4ty2j 93 12 Mini Mini NNP cord-002542-f7l4ty2j 93 13 Kit Kit NNP cord-002542-f7l4ty2j 93 14 as as IN cord-002542-f7l4ty2j 93 15 per per IN cord-002542-f7l4ty2j 93 16 the the DT cord-002542-f7l4ty2j 93 17 manufacturer manufacturer NN cord-002542-f7l4ty2j 93 18 's 's POS cord-002542-f7l4ty2j 93 19 protocol protocol NN cord-002542-f7l4ty2j 93 20 . . . cord-002542-f7l4ty2j 94 1 Next next JJ cord-002542-f7l4ty2j 94 2 generation generation NN cord-002542-f7l4ty2j 94 3 sequencing sequencing NN cord-002542-f7l4ty2j 94 4 ( ( -LRB- cord-002542-f7l4ty2j 94 5 NGS NGS NNP cord-002542-f7l4ty2j 94 6 ) ) -RRB- cord-002542-f7l4ty2j 94 7 libraries library NNS cord-002542-f7l4ty2j 94 8 were be VBD cord-002542-f7l4ty2j 94 9 generated generate VBN cord-002542-f7l4ty2j 94 10 using use VBG cord-002542-f7l4ty2j 94 11 100ng 100ng NNP cord-002542-f7l4ty2j 94 12 of of IN cord-002542-f7l4ty2j 94 13 RNA RNA NNP cord-002542-f7l4ty2j 94 14 using use VBG cord-002542-f7l4ty2j 94 15 the the DT cord-002542-f7l4ty2j 94 16 ' ' `` cord-002542-f7l4ty2j 94 17 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 94 18 ' ' '' cord-002542-f7l4ty2j 94 19 protocol protocol NN cord-002542-f7l4ty2j 94 20 as as IN cord-002542-f7l4ty2j 94 21 previously previously RB cord-002542-f7l4ty2j 94 22 described describe VBN cord-002542-f7l4ty2j 94 23 by by IN cord-002542-f7l4ty2j 94 24 Routh Routh NNP cord-002542-f7l4ty2j 94 25 et et NNP cord-002542-f7l4ty2j 94 26 al al NNP cord-002542-f7l4ty2j 94 27 . . . cord-002542-f7l4ty2j 95 1 [ [ -LRB- cord-002542-f7l4ty2j 95 2 35 35 CD cord-002542-f7l4ty2j 95 3 , , , cord-002542-f7l4ty2j 95 4 44 44 CD cord-002542-f7l4ty2j 95 5 , , , cord-002542-f7l4ty2j 95 6 45 45 CD cord-002542-f7l4ty2j 95 7 ] ] -RRB- cord-002542-f7l4ty2j 95 8 . . . cord-002542-f7l4ty2j 96 1 Briefly briefly RB cord-002542-f7l4ty2j 96 2 , , , cord-002542-f7l4ty2j 96 3 cDNA cDNA NNP cord-002542-f7l4ty2j 96 4 is be VBZ cord-002542-f7l4ty2j 96 5 synthesized synthesize VBN cord-002542-f7l4ty2j 96 6 through through IN cord-002542-f7l4ty2j 96 7 RT RT NNP cord-002542-f7l4ty2j 96 8 - - HYPH cord-002542-f7l4ty2j 96 9 PCR PCR NNP cord-002542-f7l4ty2j 96 10 initiated initiate VBD cord-002542-f7l4ty2j 96 11 from from IN cord-002542-f7l4ty2j 96 12 semi semi JJ cord-002542-f7l4ty2j 96 13 - - JJ cord-002542-f7l4ty2j 96 14 random random JJ cord-002542-f7l4ty2j 96 15 ( ( -LRB- cord-002542-f7l4ty2j 96 16 6N 6n NN cord-002542-f7l4ty2j 96 17 ) ) -RRB- cord-002542-f7l4ty2j 96 18 primers primer NNS cord-002542-f7l4ty2j 96 19 containing contain VBG cord-002542-f7l4ty2j 96 20 a a DT cord-002542-f7l4ty2j 96 21 partial partial JJ cord-002542-f7l4ty2j 96 22 Illumina Illumina NNP cord-002542-f7l4ty2j 96 23 p7 p7 NN cord-002542-f7l4ty2j 96 24 adapter adapter NN cord-002542-f7l4ty2j 96 25 ( ( -LRB- cord-002542-f7l4ty2j 96 26 GTGACTGGAGTTCAGACGTGTGCTCTTCCGATCTNNNNNN GTGACTGGAGTTCAGACGTGTGCTCTTCCGATCTNNNNNN NNP cord-002542-f7l4ty2j 96 27 ) ) -RRB- cord-002542-f7l4ty2j 96 28 and and CC cord-002542-f7l4ty2j 96 29 stochastically stochastically RB cord-002542-f7l4ty2j 96 30 terminated terminate VBN cord-002542-f7l4ty2j 96 31 by by IN cord-002542-f7l4ty2j 96 32 the the DT cord-002542-f7l4ty2j 96 33 addition addition NN cord-002542-f7l4ty2j 96 34 of of IN cord-002542-f7l4ty2j 96 35 azido azido NNP cord-002542-f7l4ty2j 96 36 - - HYPH cord-002542-f7l4ty2j 96 37 NTPs NTPs NNP cord-002542-f7l4ty2j 96 38 ( ( -LRB- cord-002542-f7l4ty2j 96 39 AzNTP AzNTP NNP cord-002542-f7l4ty2j 96 40 ) ) -RRB- cord-002542-f7l4ty2j 96 41 at at IN cord-002542-f7l4ty2j 96 42 a a DT cord-002542-f7l4ty2j 96 43 ratio ratio NN cord-002542-f7l4ty2j 96 44 of of IN cord-002542-f7l4ty2j 96 45 1:35 1:35 CD cord-002542-f7l4ty2j 97 1 AzNTP azntp NN cord-002542-f7l4ty2j 97 2 : : : cord-002542-f7l4ty2j 97 3 dNTPs dntp NNS cord-002542-f7l4ty2j 97 4 . . . cord-002542-f7l4ty2j 98 1 Subsequently subsequently RB cord-002542-f7l4ty2j 98 2 , , , cord-002542-f7l4ty2j 98 3 the the DT cord-002542-f7l4ty2j 98 4 p5 p5 NNP cord-002542-f7l4ty2j 98 5 Click Click NNP cord-002542-f7l4ty2j 98 6 - - HYPH cord-002542-f7l4ty2j 98 7 Adapter Adapter NNP cord-002542-f7l4ty2j 98 8 ( ( -LRB- cord-002542-f7l4ty2j 98 9 5'-Hexynyl 5'-hexynyl CD cord-002542-f7l4ty2j 98 10 - - HYPH cord-002542-f7l4ty2j 98 11 NNNNAGATCGGAAGAGCGTCGTGTA NNNNAGATCGGAAGAGCGTCGTGTA NNP cord-002542-f7l4ty2j 98 12 GGGAAAGAGTGTAGATCTCGGTGGTCGCCGTATCATT GGGAAAGAGTGTAGATCTCGGTGGTCGCCGTATCATT NNP cord-002542-f7l4ty2j 98 13 , , , cord-002542-f7l4ty2j 98 14 IDT IDT NNP cord-002542-f7l4ty2j 98 15 ) ) -RRB- cord-002542-f7l4ty2j 98 16 was be VBD cord-002542-f7l4ty2j 98 17 click click NN cord-002542-f7l4ty2j 98 18 - - HYPH cord-002542-f7l4ty2j 98 19 ligated ligate VBN cord-002542-f7l4ty2j 98 20 onto onto IN cord-002542-f7l4ty2j 98 21 the the DT cord-002542-f7l4ty2j 98 22 azido azido NNP cord-002542-f7l4ty2j 98 23 - - HYPH cord-002542-f7l4ty2j 98 24 terminated terminate VBN cord-002542-f7l4ty2j 98 25 cDNA cdna NN cord-002542-f7l4ty2j 98 26 fragment fragment NN cord-002542-f7l4ty2j 98 27 using use VBG cord-002542-f7l4ty2j 98 28 copper copper NN cord-002542-f7l4ty2j 98 29 - - HYPH cord-002542-f7l4ty2j 98 30 catalysed catalyse VBN cord-002542-f7l4ty2j 98 31 azide azide NN cord-002542-f7l4ty2j 98 32 - - HYPH cord-002542-f7l4ty2j 98 33 alkyne alkyne NN cord-002542-f7l4ty2j 98 34 cycloaddition cycloaddition NN cord-002542-f7l4ty2j 98 35 ( ( -LRB- cord-002542-f7l4ty2j 98 36 CuAAC CuAAC NNP cord-002542-f7l4ty2j 98 37 ) ) -RRB- cord-002542-f7l4ty2j 98 38 in in IN cord-002542-f7l4ty2j 98 39 the the DT cord-002542-f7l4ty2j 98 40 presence presence NN cord-002542-f7l4ty2j 98 41 of of IN cord-002542-f7l4ty2j 98 42 TBTA TBTA NNP cord-002542-f7l4ty2j 98 43 ligand ligand NN cord-002542-f7l4ty2j 98 44 ( ( -LRB- cord-002542-f7l4ty2j 98 45 Lumiprobe Lumiprobe NNP cord-002542-f7l4ty2j 98 46 ) ) -RRB- cord-002542-f7l4ty2j 98 47 and and CC cord-002542-f7l4ty2j 98 48 Vitamin vitamin NN cord-002542-f7l4ty2j 98 49 C c NN cord-002542-f7l4ty2j 98 50 catalyst catalyst NN cord-002542-f7l4ty2j 98 51 in in IN cord-002542-f7l4ty2j 98 52 55 55 CD cord-002542-f7l4ty2j 98 53 % % NN cord-002542-f7l4ty2j 98 54 DMSO DMSO NNP cord-002542-f7l4ty2j 98 55 . . . cord-002542-f7l4ty2j 99 1 After after IN cord-002542-f7l4ty2j 99 2 purifying purify VBG cord-002542-f7l4ty2j 99 3 the the DT cord-002542-f7l4ty2j 99 4 click click NN cord-002542-f7l4ty2j 99 5 - - HYPH cord-002542-f7l4ty2j 99 6 linked link VBN cord-002542-f7l4ty2j 99 7 cDNA cdna NN cord-002542-f7l4ty2j 99 8 with with IN cord-002542-f7l4ty2j 99 9 a a DT cord-002542-f7l4ty2j 99 10 Zymo Zymo NNP cord-002542-f7l4ty2j 99 11 DNA dna NN cord-002542-f7l4ty2j 99 12 clean clean JJ cord-002542-f7l4ty2j 99 13 column column NN cord-002542-f7l4ty2j 99 14 , , , cord-002542-f7l4ty2j 99 15 18 18 CD cord-002542-f7l4ty2j 99 16 cycles cycle NNS cord-002542-f7l4ty2j 99 17 of of IN cord-002542-f7l4ty2j 99 18 OneTaq OneTaq NNP cord-002542-f7l4ty2j 99 19 ( ( -LRB- cord-002542-f7l4ty2j 99 20 NEB NEB NNP cord-002542-f7l4ty2j 99 21 ) ) -RRB- cord-002542-f7l4ty2j 99 22 PCR PCR NNP cord-002542-f7l4ty2j 99 23 amplification amplification NN cord-002542-f7l4ty2j 99 24 adds add VBZ cord-002542-f7l4ty2j 99 25 the the DT cord-002542-f7l4ty2j 99 26 remainder remainder NN cord-002542-f7l4ty2j 99 27 of of IN cord-002542-f7l4ty2j 99 28 the the DT cord-002542-f7l4ty2j 99 29 p7 p7 NN cord-002542-f7l4ty2j 99 30 adapter adapter NN cord-002542-f7l4ty2j 99 31 along along IN cord-002542-f7l4ty2j 99 32 with with IN cord-002542-f7l4ty2j 99 33 the the DT cord-002542-f7l4ty2j 99 34 desired desire VBN cord-002542-f7l4ty2j 99 35 TruSeq TruSeq NNP cord-002542-f7l4ty2j 99 36 index index NN cord-002542-f7l4ty2j 99 37 sequence sequence NN cord-002542-f7l4ty2j 99 38 . . . cord-002542-f7l4ty2j 100 1 PCR PCR NNP cord-002542-f7l4ty2j 100 2 product product NN cord-002542-f7l4ty2j 100 3 was be VBD cord-002542-f7l4ty2j 100 4 cleaned clean VBN cord-002542-f7l4ty2j 100 5 again again RB cord-002542-f7l4ty2j 100 6 with with IN cord-002542-f7l4ty2j 100 7 a a DT cord-002542-f7l4ty2j 100 8 Zymo Zymo NNP cord-002542-f7l4ty2j 100 9 DNA dna NN cord-002542-f7l4ty2j 100 10 clean clean JJ cord-002542-f7l4ty2j 100 11 column column NN cord-002542-f7l4ty2j 100 12 to to TO cord-002542-f7l4ty2j 100 13 remove remove VB cord-002542-f7l4ty2j 100 14 excess excess JJ cord-002542-f7l4ty2j 100 15 primers primer NNS cord-002542-f7l4ty2j 100 16 and and CC cord-002542-f7l4ty2j 100 17 then then RB cord-002542-f7l4ty2j 100 18 ran run VBD cord-002542-f7l4ty2j 100 19 on on IN cord-002542-f7l4ty2j 100 20 a a DT cord-002542-f7l4ty2j 100 21 1 1 CD cord-002542-f7l4ty2j 100 22 - - SYM cord-002542-f7l4ty2j 100 23 2 2 CD cord-002542-f7l4ty2j 100 24 % % NN cord-002542-f7l4ty2j 100 25 precast precast NN cord-002542-f7l4ty2j 100 26 agarose agarose NN cord-002542-f7l4ty2j 100 27 e e NN cord-002542-f7l4ty2j 100 28 - - NN cord-002542-f7l4ty2j 100 29 gel gel NN cord-002542-f7l4ty2j 100 30 ( ( -LRB- cord-002542-f7l4ty2j 100 31 Invitrogen Invitrogen NNP cord-002542-f7l4ty2j 100 32 , , , cord-002542-f7l4ty2j 100 33 E E NNP cord-002542-f7l4ty2j 100 34 - - HYPH cord-002542-f7l4ty2j 100 35 Gel Gel NNP cord-002542-f7l4ty2j 100 36 Electrophoresis Electrophoresis NNP cord-002542-f7l4ty2j 100 37 System System NNP cord-002542-f7l4ty2j 100 38 ) ) -RRB- cord-002542-f7l4ty2j 100 39 . . . cord-002542-f7l4ty2j 101 1 cDNA cDNA NNP cord-002542-f7l4ty2j 101 2 libraries library NNS cord-002542-f7l4ty2j 101 3 between between IN cord-002542-f7l4ty2j 101 4 400 400 CD cord-002542-f7l4ty2j 101 5 to to IN cord-002542-f7l4ty2j 101 6 700bp 700bp NNP cord-002542-f7l4ty2j 101 7 were be VBD cord-002542-f7l4ty2j 101 8 excised excise VBN cord-002542-f7l4ty2j 101 9 corresponding correspond VBG cord-002542-f7l4ty2j 101 10 to to TO cord-002542-f7l4ty2j 101 11 insert insert VB cord-002542-f7l4ty2j 101 12 sizes size NNS cord-002542-f7l4ty2j 101 13 of of IN cord-002542-f7l4ty2j 101 14 250 250 CD cord-002542-f7l4ty2j 101 15 - - HYPH cord-002542-f7l4ty2j 101 16 550bp 550bp NN cord-002542-f7l4ty2j 101 17 and and CC cord-002542-f7l4ty2j 101 18 cleaned clean VBD cord-002542-f7l4ty2j 101 19 using use VBG cord-002542-f7l4ty2j 101 20 the the DT cord-002542-f7l4ty2j 101 21 Zymo Zymo NNP cord-002542-f7l4ty2j 101 22 Research Research NNP cord-002542-f7l4ty2j 101 23 Gel Gel NNP cord-002542-f7l4ty2j 101 24 DNA DNA NNP cord-002542-f7l4ty2j 101 25 Recovery Recovery NNP cord-002542-f7l4ty2j 101 26 Kit kit NN cord-002542-f7l4ty2j 101 27 . . . cord-002542-f7l4ty2j 102 1 Final final JJ cord-002542-f7l4ty2j 102 2 cDNA cdna NN cord-002542-f7l4ty2j 102 3 libraries library NNS cord-002542-f7l4ty2j 102 4 were be VBD cord-002542-f7l4ty2j 102 5 quantified quantify VBN cord-002542-f7l4ty2j 102 6 using use VBG cord-002542-f7l4ty2j 102 7 a a DT cord-002542-f7l4ty2j 102 8 QuBit QuBit NNP cord-002542-f7l4ty2j 102 9 fluorimeter fluorimeter NN cord-002542-f7l4ty2j 102 10 ( ( -LRB- cord-002542-f7l4ty2j 102 11 Life Life NNP cord-002542-f7l4ty2j 102 12 Tech Tech NNP cord-002542-f7l4ty2j 102 13 ) ) -RRB- cord-002542-f7l4ty2j 102 14 and and CC cord-002542-f7l4ty2j 102 15 loaded load VBN cord-002542-f7l4ty2j 102 16 on on IN cord-002542-f7l4ty2j 102 17 a a DT cord-002542-f7l4ty2j 102 18 HiSeq HiSeq NNP cord-002542-f7l4ty2j 102 19 1500 1500 CD cord-002542-f7l4ty2j 102 20 single single JJ cord-002542-f7l4ty2j 102 21 read read NN cord-002542-f7l4ty2j 102 22 rapid rapid JJ cord-002542-f7l4ty2j 102 23 run run NN cord-002542-f7l4ty2j 102 24 flowcell flowcell NNP cord-002542-f7l4ty2j 102 25 for for IN cord-002542-f7l4ty2j 102 26 1x150 1x150 CD cord-002542-f7l4ty2j 102 27 reads read NNS cord-002542-f7l4ty2j 102 28 and and CC cord-002542-f7l4ty2j 102 29 7 7 CD cord-002542-f7l4ty2j 102 30 nucleotides nucleotide NNS cord-002542-f7l4ty2j 102 31 of of IN cord-002542-f7l4ty2j 102 32 the the DT cord-002542-f7l4ty2j 102 33 index index NN cord-002542-f7l4ty2j 102 34 . . . cord-002542-f7l4ty2j 103 1 FHV FHV NNP cord-002542-f7l4ty2j 103 2 libraries library NNS cord-002542-f7l4ty2j 103 3 used use VBN cord-002542-f7l4ty2j 103 4 for for IN cord-002542-f7l4ty2j 103 5 the the DT cord-002542-f7l4ty2j 103 6 triplicate triplicate JJ cord-002542-f7l4ty2j 103 7 study study NN cord-002542-f7l4ty2j 103 8 shown show VBN cord-002542-f7l4ty2j 103 9 in in IN cord-002542-f7l4ty2j 103 10 S2 S2 NNP cord-002542-f7l4ty2j 103 11 Fig Fig NNP cord-002542-f7l4ty2j 103 12 were be VBD cord-002542-f7l4ty2j 103 13 sequenced sequence VBN cord-002542-f7l4ty2j 103 14 on on IN cord-002542-f7l4ty2j 103 15 a a DT cord-002542-f7l4ty2j 103 16 MiSeq MiSeq NNP cord-002542-f7l4ty2j 103 17 platform platform NN cord-002542-f7l4ty2j 103 18 with with IN cord-002542-f7l4ty2j 103 19 v3 v3 NN cord-002542-f7l4ty2j 103 20 chemistry chemistry NN cord-002542-f7l4ty2j 103 21 for for IN cord-002542-f7l4ty2j 103 22 600 600 CD cord-002542-f7l4ty2j 103 23 cycles cycle NNS cord-002542-f7l4ty2j 103 24 ( ( -LRB- cord-002542-f7l4ty2j 103 25 2x300 2x300 CD cord-002542-f7l4ty2j 103 26 ) ) -RRB- cord-002542-f7l4ty2j 103 27 . . . cord-002542-f7l4ty2j 104 1 Reads read NNS cord-002542-f7l4ty2j 104 2 were be VBD cord-002542-f7l4ty2j 104 3 trimmed trim VBN cord-002542-f7l4ty2j 104 4 to to IN cord-002542-f7l4ty2j 104 5 150nts 150nts CD cord-002542-f7l4ty2j 104 6 prior prior RB cord-002542-f7l4ty2j 104 7 to to IN cord-002542-f7l4ty2j 104 8 analysis analysis NN cord-002542-f7l4ty2j 104 9 to to TO cord-002542-f7l4ty2j 104 10 emulate emulate VB cord-002542-f7l4ty2j 104 11 the the DT cord-002542-f7l4ty2j 104 12 libraries library NNS cord-002542-f7l4ty2j 104 13 sequenced sequence VBN cord-002542-f7l4ty2j 104 14 on on IN cord-002542-f7l4ty2j 104 15 the the DT cord-002542-f7l4ty2j 104 16 HiSeq HiSeq NNP cord-002542-f7l4ty2j 104 17 . . . cord-002542-f7l4ty2j 105 1 Raw raw JJ cord-002542-f7l4ty2j 105 2 reads read NNS cord-002542-f7l4ty2j 105 3 were be VBD cord-002542-f7l4ty2j 105 4 processed process VBN cord-002542-f7l4ty2j 105 5 by by IN cord-002542-f7l4ty2j 105 6 first first RB cord-002542-f7l4ty2j 105 7 removing remove VBG cord-002542-f7l4ty2j 105 8 the the DT cord-002542-f7l4ty2j 105 9 Illumina Illumina NNP cord-002542-f7l4ty2j 105 10 TruSeq TruSeq NNP cord-002542-f7l4ty2j 105 11 adaptor adaptor NN cord-002542-f7l4ty2j 105 12 using use VBG cord-002542-f7l4ty2j 105 13 Cutadapt Cutadapt NNP cord-002542-f7l4ty2j 105 14 [ [ -LRB- cord-002542-f7l4ty2j 105 15 46 46 CD cord-002542-f7l4ty2j 105 16 ] ] -RRB- cord-002542-f7l4ty2j 105 17 with with IN cord-002542-f7l4ty2j 105 18 default default NN cord-002542-f7l4ty2j 105 19 parameters parameter NNS cord-002542-f7l4ty2j 105 20 . . . cord-002542-f7l4ty2j 106 1 Next next RB cord-002542-f7l4ty2j 106 2 , , , cord-002542-f7l4ty2j 106 3 the the DT cord-002542-f7l4ty2j 106 4 first first JJ cord-002542-f7l4ty2j 106 5 6 6 CD cord-002542-f7l4ty2j 106 6 nucleotides nucleotide NNS cord-002542-f7l4ty2j 106 7 ( ( -LRB- cord-002542-f7l4ty2j 106 8 corresponding correspond VBG cord-002542-f7l4ty2j 106 9 to to IN cord-002542-f7l4ty2j 106 10 the the DT cord-002542-f7l4ty2j 106 11 random random JJ cord-002542-f7l4ty2j 106 12 nucleotides nucleotide NNS cord-002542-f7l4ty2j 106 13 and and CC cord-002542-f7l4ty2j 106 14 triazole triazole NN cord-002542-f7l4ty2j 106 15 - - HYPH cord-002542-f7l4ty2j 106 16 linkage linkage NN cord-002542-f7l4ty2j 106 17 included include VBN cord-002542-f7l4ty2j 106 18 in in IN cord-002542-f7l4ty2j 106 19 the the DT cord-002542-f7l4ty2j 106 20 Click Click NNP cord-002542-f7l4ty2j 106 21 - - HYPH cord-002542-f7l4ty2j 106 22 Adaptor Adaptor NNP cord-002542-f7l4ty2j 106 23 ) ) -RRB- cord-002542-f7l4ty2j 106 24 were be VBD cord-002542-f7l4ty2j 106 25 trimmed trim VBN cord-002542-f7l4ty2j 106 26 and and CC cord-002542-f7l4ty2j 106 27 any any DT cord-002542-f7l4ty2j 106 28 reads read NNS cord-002542-f7l4ty2j 106 29 that that WDT cord-002542-f7l4ty2j 106 30 contained contain VBD cord-002542-f7l4ty2j 106 31 nucleotides nucleotide NNS cord-002542-f7l4ty2j 106 32 with with IN cord-002542-f7l4ty2j 106 33 a a DT cord-002542-f7l4ty2j 106 34 PHRED PHRED NNP cord-002542-f7l4ty2j 106 35 score score NN cord-002542-f7l4ty2j 106 36 < < XX cord-002542-f7l4ty2j 106 37 20 20 CD cord-002542-f7l4ty2j 106 38 were be VBD cord-002542-f7l4ty2j 106 39 removed remove VBN cord-002542-f7l4ty2j 106 40 using use VBG cord-002542-f7l4ty2j 106 41 the the DT cord-002542-f7l4ty2j 106 42 FASTX FASTX NNP cord-002542-f7l4ty2j 106 43 toolkit toolkit NN cord-002542-f7l4ty2j 106 44 ( ( -LRB- cord-002542-f7l4ty2j 106 45 http://hannonlab.cshl.edu/fastx_toolkit/ http://hannonlab.cshl.edu/fastx_toolkit/ NNP cord-002542-f7l4ty2j 106 46 ) ) -RRB- cord-002542-f7l4ty2j 106 47 . . . cord-002542-f7l4ty2j 107 1 The the DT cord-002542-f7l4ty2j 107 2 remaining remain VBG cord-002542-f7l4ty2j 107 3 reads read NNS cord-002542-f7l4ty2j 107 4 were be VBD cord-002542-f7l4ty2j 107 5 aligned align VBN cord-002542-f7l4ty2j 107 6 end end NN cord-002542-f7l4ty2j 107 7 - - HYPH cord-002542-f7l4ty2j 107 8 to to IN cord-002542-f7l4ty2j 107 9 - - HYPH cord-002542-f7l4ty2j 107 10 end end NN cord-002542-f7l4ty2j 107 11 with with IN cord-002542-f7l4ty2j 107 12 Bowtie Bowtie NNP cord-002542-f7l4ty2j 107 13 ( ( -LRB- cord-002542-f7l4ty2j 107 14 v1.0.1 v1.0.1 NNP cord-002542-f7l4ty2j 107 15 ) ) -RRB- cord-002542-f7l4ty2j 108 1 [ [ -LRB- cord-002542-f7l4ty2j 108 2 47 47 CD cord-002542-f7l4ty2j 108 3 ] ] -RRB- cord-002542-f7l4ty2j 109 1 ( ( -LRB- cord-002542-f7l4ty2j 109 2 command command NN cord-002542-f7l4ty2j 109 3 line line NN cord-002542-f7l4ty2j 109 4 parameters parameter NNS cord-002542-f7l4ty2j 109 5 : : : cord-002542-f7l4ty2j 110 1 -v -v JJS cord-002542-f7l4ty2j 110 2 3 3 CD cord-002542-f7l4ty2j 110 3 --best --b JJS cord-002542-f7l4ty2j 110 4 ) ) -RRB- cord-002542-f7l4ty2j 111 1 first first RB cord-002542-f7l4ty2j 111 2 to to IN cord-002542-f7l4ty2j 111 3 the the DT cord-002542-f7l4ty2j 111 4 FHV FHV NNP cord-002542-f7l4ty2j 111 5 genome genome NN cord-002542-f7l4ty2j 112 1 ( ( -LRB- cord-002542-f7l4ty2j 112 2 NC_004414 NC_004414 NNP cord-002542-f7l4ty2j 112 3 and and CC cord-002542-f7l4ty2j 112 4 NC_004146 NC_004146 NNP cord-002542-f7l4ty2j 112 5 ) ) -RRB- cord-002542-f7l4ty2j 112 6 and and CC cord-002542-f7l4ty2j 112 7 next next JJ cord-002542-f7l4ty2j 112 8 to to TO cord-002542-f7l4ty2j 112 9 host host VB cord-002542-f7l4ty2j 112 10 D. D. NNP cord-002542-f7l4ty2j 112 11 melanogaster melanogaster NN cord-002542-f7l4ty2j 112 12 genome genome NNP cord-002542-f7l4ty2j 112 13 ( ( -LRB- cord-002542-f7l4ty2j 112 14 fb5_22 fb5_22 NN cord-002542-f7l4ty2j 112 15 ) ) -RRB- cord-002542-f7l4ty2j 112 16 . . . cord-002542-f7l4ty2j 113 1 The the DT cord-002542-f7l4ty2j 113 2 remaining remain VBG cord-002542-f7l4ty2j 113 3 unmapped unmapped JJ cord-002542-f7l4ty2j 113 4 reads read NNS cord-002542-f7l4ty2j 113 5 were be VBD cord-002542-f7l4ty2j 113 6 processed process VBN cord-002542-f7l4ty2j 113 7 to to TO cord-002542-f7l4ty2j 113 8 identify identify VB cord-002542-f7l4ty2j 113 9 recombination recombination NN cord-002542-f7l4ty2j 113 10 events event NNS cord-002542-f7l4ty2j 113 11 using use VBG cord-002542-f7l4ty2j 113 12 the the DT cord-002542-f7l4ty2j 113 13 python python NNP cord-002542-f7l4ty2j 113 14 script script NN cord-002542-f7l4ty2j 113 15 ' ' `` cord-002542-f7l4ty2j 113 16 ViReMa virema UH cord-002542-f7l4ty2j 113 17 ' ' '' cord-002542-f7l4ty2j 113 18 ( ( -LRB- cord-002542-f7l4ty2j 113 19 Viral Viral NNP cord-002542-f7l4ty2j 113 20 Recombination Recombination NNP cord-002542-f7l4ty2j 113 21 Mapper Mapper NNP cord-002542-f7l4ty2j 113 22 ) ) -RRB- cord-002542-f7l4ty2j 113 23 [ [ -LRB- cord-002542-f7l4ty2j 113 24 32 32 CD cord-002542-f7l4ty2j 113 25 ] ] -RRB- cord-002542-f7l4ty2j 114 1 ( ( -LRB- cord-002542-f7l4ty2j 114 2 command command NN cord-002542-f7l4ty2j 114 3 line line NN cord-002542-f7l4ty2j 114 4 parameters:--N parameters:--n ADD cord-002542-f7l4ty2j 114 5 1 1 CD cord-002542-f7l4ty2j 114 6 --X --x CD cord-002542-f7l4ty2j 114 7 5 5 CD cord-002542-f7l4ty2j 115 1 --Seed --seed CD cord-002542-f7l4ty2j 115 2 25 25 CD cord-002542-f7l4ty2j 115 3 --Host_Seed --host_seed SYM cord-002542-f7l4ty2j 115 4 30 30 CD cord-002542-f7l4ty2j 115 5 --Defuzz --defuzz CD cord-002542-f7l4ty2j 115 6 0 0 CD cord-002542-f7l4ty2j 115 7 --MicroInDel --microindel CD cord-002542-f7l4ty2j 115 8 5 5 CD cord-002542-f7l4ty2j 115 9 ) ) -RRB- cord-002542-f7l4ty2j 115 10 . . . cord-002542-f7l4ty2j 116 1 The the DT cord-002542-f7l4ty2j 116 2 frequency frequency NN cord-002542-f7l4ty2j 116 3 of of IN cord-002542-f7l4ty2j 116 4 a a DT cord-002542-f7l4ty2j 116 5 specific specific JJ cord-002542-f7l4ty2j 116 6 recombination recombination NN cord-002542-f7l4ty2j 116 7 event event NN cord-002542-f7l4ty2j 116 8 is be VBZ cord-002542-f7l4ty2j 116 9 approximated approximate VBN cord-002542-f7l4ty2j 116 10 by by IN cord-002542-f7l4ty2j 116 11 dividing divide VBG cord-002542-f7l4ty2j 116 12 the the DT cord-002542-f7l4ty2j 116 13 number number NN cord-002542-f7l4ty2j 116 14 of of IN cord-002542-f7l4ty2j 116 15 reads read NNS cord-002542-f7l4ty2j 116 16 mapping mapping NN cord-002542-f7l4ty2j 116 17 to to IN cord-002542-f7l4ty2j 116 18 this this DT cord-002542-f7l4ty2j 116 19 recombination recombination NN cord-002542-f7l4ty2j 116 20 ( ( -LRB- cord-002542-f7l4ty2j 116 21 N N NNP cord-002542-f7l4ty2j 116 22 ) ) -RRB- cord-002542-f7l4ty2j 116 23 by by IN cord-002542-f7l4ty2j 116 24 N n CD cord-002542-f7l4ty2j 116 25 plus plus CC cord-002542-f7l4ty2j 116 26 the the DT cord-002542-f7l4ty2j 116 27 average average NN cord-002542-f7l4ty2j 116 28 of of IN cord-002542-f7l4ty2j 116 29 the the DT cord-002542-f7l4ty2j 116 30 number number NN cord-002542-f7l4ty2j 116 31 of of IN cord-002542-f7l4ty2j 116 32 reads read NNS cord-002542-f7l4ty2j 116 33 mapping mapping NN cord-002542-f7l4ty2j 116 34 to to IN cord-002542-f7l4ty2j 116 35 the the DT cord-002542-f7l4ty2j 116 36 wild wild JJ cord-002542-f7l4ty2j 116 37 - - HYPH cord-002542-f7l4ty2j 116 38 type type NN cord-002542-f7l4ty2j 116 39 genome genome NN cord-002542-f7l4ty2j 116 40 at at IN cord-002542-f7l4ty2j 116 41 each each DT cord-002542-f7l4ty2j 116 42 of of IN cord-002542-f7l4ty2j 116 43 the the DT cord-002542-f7l4ty2j 116 44 recombination recombination NN cord-002542-f7l4ty2j 116 45 coordinates coordinate VBZ cord-002542-f7l4ty2j 116 46 . . . cord-002542-f7l4ty2j 117 1 The the DT cord-002542-f7l4ty2j 117 2 Oxford Oxford NNP cord-002542-f7l4ty2j 117 3 Nanopore Nanopore NNP cord-002542-f7l4ty2j 117 4 Technologies Technologies NNPS cord-002542-f7l4ty2j 117 5 's 's POS cord-002542-f7l4ty2j 117 6 ( ( -LRB- cord-002542-f7l4ty2j 117 7 ONT ONT NNP cord-002542-f7l4ty2j 117 8 ) ) -RRB- cord-002542-f7l4ty2j 117 9 MinION MinION NNP cord-002542-f7l4ty2j 117 10 and and CC cord-002542-f7l4ty2j 117 11 flowcells flowcell NNS cord-002542-f7l4ty2j 117 12 were be VBD cord-002542-f7l4ty2j 117 13 acquired acquire VBN cord-002542-f7l4ty2j 117 14 as as IN cord-002542-f7l4ty2j 117 15 part part NN cord-002542-f7l4ty2j 117 16 of of IN cord-002542-f7l4ty2j 117 17 the the DT cord-002542-f7l4ty2j 117 18 ONT ONT NNP cord-002542-f7l4ty2j 117 19 early early JJ cord-002542-f7l4ty2j 117 20 - - HYPH cord-002542-f7l4ty2j 117 21 access access NN cord-002542-f7l4ty2j 117 22 program program NN cord-002542-f7l4ty2j 117 23 . . . cord-002542-f7l4ty2j 118 1 To to TO cord-002542-f7l4ty2j 118 2 prepare prepare VB cord-002542-f7l4ty2j 118 3 sequencing sequencing NN cord-002542-f7l4ty2j 118 4 libraries library NNS cord-002542-f7l4ty2j 118 5 for for IN cord-002542-f7l4ty2j 118 6 the the DT cord-002542-f7l4ty2j 118 7 MinION minion NN cord-002542-f7l4ty2j 118 8 , , , cord-002542-f7l4ty2j 118 9 50ng 50ng NN cord-002542-f7l4ty2j 118 10 of of IN cord-002542-f7l4ty2j 118 11 RNA RNA NNP cord-002542-f7l4ty2j 118 12 was be VBD cord-002542-f7l4ty2j 118 13 reverse reverse RB cord-002542-f7l4ty2j 118 14 transcribed transcribe VBN cord-002542-f7l4ty2j 118 15 using use VBG cord-002542-f7l4ty2j 118 16 RNA RNA NNP cord-002542-f7l4ty2j 118 17 specific specific JJ cord-002542-f7l4ty2j 118 18 primers primer NNS cord-002542-f7l4ty2j 118 19 that that WDT cord-002542-f7l4ty2j 118 20 were be VBD cord-002542-f7l4ty2j 118 21 complimentary complimentary JJ cord-002542-f7l4ty2j 118 22 to to IN cord-002542-f7l4ty2j 118 23 the the DT cord-002542-f7l4ty2j 118 24 3 3 CD cord-002542-f7l4ty2j 118 25 ' ' NN cord-002542-f7l4ty2j 118 26 end end NN cord-002542-f7l4ty2j 118 27 of of IN cord-002542-f7l4ty2j 118 28 the the DT cord-002542-f7l4ty2j 118 29 respective respective JJ cord-002542-f7l4ty2j 118 30 genome genome NN cord-002542-f7l4ty2j 118 31 ( ( -LRB- cord-002542-f7l4ty2j 118 32 RNA1_RP rna1_rp NN cord-002542-f7l4ty2j 118 33 : : : cord-002542-f7l4ty2j 118 34 ACCTCTGCCCTTTCGGGCTA ACCTCTGCCCTTTCGGGCTA NNP cord-002542-f7l4ty2j 118 35 or or CC cord-002542-f7l4ty2j 118 36 RNA2_RP rna2_rp NN cord-002542-f7l4ty2j 118 37 : : : cord-002542-f7l4ty2j 118 38 ACCTT ACCTT NNP cord-002542-f7l4ty2j 118 39 AGTCTGTTGACTTAA AGTCTGTTGACTTAA NNP cord-002542-f7l4ty2j 118 40 ) ) -RRB- cord-002542-f7l4ty2j 118 41 . . . cord-002542-f7l4ty2j 119 1 cDNA cDNA NNP cord-002542-f7l4ty2j 119 2 was be VBD cord-002542-f7l4ty2j 119 3 then then RB cord-002542-f7l4ty2j 119 4 amplified amplify VBN cord-002542-f7l4ty2j 119 5 using use VBG cord-002542-f7l4ty2j 119 6 the the DT cord-002542-f7l4ty2j 119 7 standard standard JJ cord-002542-f7l4ty2j 119 8 Phusion Phusion NNP cord-002542-f7l4ty2j 119 9 ( ( -LRB- cord-002542-f7l4ty2j 119 10 NEB NEB NNP cord-002542-f7l4ty2j 119 11 ) ) -RRB- cord-002542-f7l4ty2j 119 12 PCR pcr NN cord-002542-f7l4ty2j 119 13 protocol protocol NN cord-002542-f7l4ty2j 119 14 using use VBG cord-002542-f7l4ty2j 119 15 genome genome NN cord-002542-f7l4ty2j 119 16 specific specific JJ cord-002542-f7l4ty2j 119 17 primers primer NNS cord-002542-f7l4ty2j 119 18 ( ( -LRB- cord-002542-f7l4ty2j 119 19 RNA1_FP RNA1_FP NNS cord-002542-f7l4ty2j 119 20 : : : cord-002542-f7l4ty2j 119 21 GTTTTCGAAACAAATAAAAC gttttcgaaacaaataaaac NN cord-002542-f7l4ty2j 119 22 or or CC cord-002542-f7l4ty2j 119 23 RNA2_FP rna2_fp XX cord-002542-f7l4ty2j 119 24 : : : cord-002542-f7l4ty2j 119 25 GTAAACAATTCCAAGTTCCA GTAAACAATTCCAAGTTCCA NNP cord-002542-f7l4ty2j 119 26 ) ) -RRB- cord-002542-f7l4ty2j 119 27 for for IN cord-002542-f7l4ty2j 119 28 19 19 CD cord-002542-f7l4ty2j 119 29 cycles cycle NNS cord-002542-f7l4ty2j 119 30 . . . cord-002542-f7l4ty2j 120 1 Excess excess JJ cord-002542-f7l4ty2j 120 2 primers primer NNS cord-002542-f7l4ty2j 120 3 were be VBD cord-002542-f7l4ty2j 120 4 removed remove VBN cord-002542-f7l4ty2j 120 5 from from IN cord-002542-f7l4ty2j 120 6 the the DT cord-002542-f7l4ty2j 120 7 PCR PCR NNP cord-002542-f7l4ty2j 120 8 product product NN cord-002542-f7l4ty2j 120 9 using use VBG cord-002542-f7l4ty2j 120 10 AMPure AMPure NNP cord-002542-f7l4ty2j 120 11 XP XP NNP cord-002542-f7l4ty2j 120 12 beads bead NNS cord-002542-f7l4ty2j 120 13 ( ( -LRB- cord-002542-f7l4ty2j 120 14 Beckman Beckman NNP cord-002542-f7l4ty2j 120 15 Coulter Coulter NNP cord-002542-f7l4ty2j 120 16 ) ) -RRB- cord-002542-f7l4ty2j 120 17 at at IN cord-002542-f7l4ty2j 120 18 a a DT cord-002542-f7l4ty2j 120 19 ratio ratio NN cord-002542-f7l4ty2j 120 20 of of IN cord-002542-f7l4ty2j 120 21 1:1 1:1 CD cord-002542-f7l4ty2j 120 22 AMPure ampure CD cord-002542-f7l4ty2j 120 23 bead bead NN cord-002542-f7l4ty2j 120 24 : : : cord-002542-f7l4ty2j 120 25 PCR PCR NNP cord-002542-f7l4ty2j 120 26 product product NN cord-002542-f7l4ty2j 120 27 . . . cord-002542-f7l4ty2j 121 1 Samples sample NNS cord-002542-f7l4ty2j 121 2 were be VBD cord-002542-f7l4ty2j 121 3 then then RB cord-002542-f7l4ty2j 121 4 barcoded barcode VBN cord-002542-f7l4ty2j 121 5 and and CC cord-002542-f7l4ty2j 121 6 prepared prepare VBD cord-002542-f7l4ty2j 121 7 following follow VBG cord-002542-f7l4ty2j 121 8 the the DT cord-002542-f7l4ty2j 121 9 manufacture manufacture NN cord-002542-f7l4ty2j 121 10 's 's POS cord-002542-f7l4ty2j 121 11 protocol protocol NN cord-002542-f7l4ty2j 121 12 ( ( -LRB- cord-002542-f7l4ty2j 121 13 R9 R9 NNP cord-002542-f7l4ty2j 121 14 Native Native NNP cord-002542-f7l4ty2j 121 15 Barcoding Barcoding NNP cord-002542-f7l4ty2j 121 16 Kit Kit NNP cord-002542-f7l4ty2j 121 17 I -PRON- PRP cord-002542-f7l4ty2j 121 18 and and CC cord-002542-f7l4ty2j 121 19 Nanopore Nanopore NNP cord-002542-f7l4ty2j 121 20 Sequencing Sequencing NNP cord-002542-f7l4ty2j 121 21 Kit Kit NNP cord-002542-f7l4ty2j 121 22 ) ) -RRB- cord-002542-f7l4ty2j 121 23 with with IN cord-002542-f7l4ty2j 121 24 adjustments adjustment NNS cord-002542-f7l4ty2j 121 25 to to TO cord-002542-f7l4ty2j 121 26 tailor tailor VB cord-002542-f7l4ty2j 121 27 input input NN cord-002542-f7l4ty2j 121 28 cDNA cdna NN cord-002542-f7l4ty2j 121 29 quantities quantity NNS cord-002542-f7l4ty2j 121 30 . . . cord-002542-f7l4ty2j 122 1 A a DT cord-002542-f7l4ty2j 122 2 target target NN cord-002542-f7l4ty2j 122 3 of of IN cord-002542-f7l4ty2j 122 4 1ug 1ug NN cord-002542-f7l4ty2j 122 5 of of IN cord-002542-f7l4ty2j 122 6 fragmented fragmented JJ cord-002542-f7l4ty2j 122 7 DNA dna NN cord-002542-f7l4ty2j 122 8 at at IN cord-002542-f7l4ty2j 122 9 approximately approximately RB cord-002542-f7l4ty2j 122 10 8'000 8'000 CD cord-002542-f7l4ty2j 122 11 nts nts NNPS cord-002542-f7l4ty2j 122 12 is be VBZ cord-002542-f7l4ty2j 122 13 considered consider VBN cord-002542-f7l4ty2j 122 14 optimal optimal JJ cord-002542-f7l4ty2j 122 15 for for IN cord-002542-f7l4ty2j 122 16 library library NN cord-002542-f7l4ty2j 122 17 generation generation NN cord-002542-f7l4ty2j 122 18 using use VBG cord-002542-f7l4ty2j 122 19 this this DT cord-002542-f7l4ty2j 122 20 kit kit NN cord-002542-f7l4ty2j 122 21 . . . cord-002542-f7l4ty2j 123 1 The the DT cord-002542-f7l4ty2j 123 2 input input NN cord-002542-f7l4ty2j 123 3 amounts amount VBZ cord-002542-f7l4ty2j 123 4 for for IN cord-002542-f7l4ty2j 123 5 RNA1 RNA1 NNP cord-002542-f7l4ty2j 123 6 ( ( -LRB- cord-002542-f7l4ty2j 123 7 3107 3107 CD cord-002542-f7l4ty2j 123 8 bp bp NNP cord-002542-f7l4ty2j 123 9 ) ) -RRB- cord-002542-f7l4ty2j 123 10 and and CC cord-002542-f7l4ty2j 123 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 123 12 ( ( -LRB- cord-002542-f7l4ty2j 123 13 1400 1400 CD cord-002542-f7l4ty2j 123 14 bp bp NNP cord-002542-f7l4ty2j 123 15 ) ) -RRB- cord-002542-f7l4ty2j 123 16 were be VBD cord-002542-f7l4ty2j 123 17 thus thus RB cord-002542-f7l4ty2j 123 18 adjusted adjust VBN cord-002542-f7l4ty2j 123 19 to to IN cord-002542-f7l4ty2j 123 20 192ng 192ng JJ cord-002542-f7l4ty2j 123 21 and and CC cord-002542-f7l4ty2j 123 22 88ng 88ng NN cord-002542-f7l4ty2j 123 23 respectively respectively RB cord-002542-f7l4ty2j 123 24 and and CC cord-002542-f7l4ty2j 123 25 combined combine VBN cord-002542-f7l4ty2j 123 26 in in IN cord-002542-f7l4ty2j 123 27 46uL 46ul CD cord-002542-f7l4ty2j 123 28 water water NN cord-002542-f7l4ty2j 123 29 to to TO cord-002542-f7l4ty2j 123 30 maintain maintain VB cord-002542-f7l4ty2j 123 31 optimal optimal JJ cord-002542-f7l4ty2j 123 32 DNA dna NN cord-002542-f7l4ty2j 123 33 end end NN cord-002542-f7l4ty2j 123 34 molarity molarity NN cord-002542-f7l4ty2j 123 35 . . . cord-002542-f7l4ty2j 124 1 After after IN cord-002542-f7l4ty2j 124 2 ligation ligation NN cord-002542-f7l4ty2j 124 3 of of IN cord-002542-f7l4ty2j 124 4 barcodes barcode NNS cord-002542-f7l4ty2j 124 5 , , , cord-002542-f7l4ty2j 124 6 equal equal JJ cord-002542-f7l4ty2j 124 7 amount amount NN cord-002542-f7l4ty2j 124 8 of of IN cord-002542-f7l4ty2j 124 9 each each DT cord-002542-f7l4ty2j 124 10 DNA dna NN cord-002542-f7l4ty2j 124 11 library library NN cord-002542-f7l4ty2j 124 12 ( ( -LRB- cord-002542-f7l4ty2j 124 13 9 9 CD cord-002542-f7l4ty2j 124 14 samples sample NNS cord-002542-f7l4ty2j 124 15 in in IN cord-002542-f7l4ty2j 124 16 total total NN cord-002542-f7l4ty2j 124 17 ) ) -RRB- cord-002542-f7l4ty2j 124 18 were be VBD cord-002542-f7l4ty2j 124 19 pooled pool VBN cord-002542-f7l4ty2j 124 20 and and CC cord-002542-f7l4ty2j 124 21 loaded load VBN cord-002542-f7l4ty2j 124 22 onto onto IN cord-002542-f7l4ty2j 124 23 a a DT cord-002542-f7l4ty2j 124 24 MinION MinION NNP cord-002542-f7l4ty2j 124 25 MkIB MkIB NNP cord-002542-f7l4ty2j 124 26 device device NN cord-002542-f7l4ty2j 124 27 equipped equip VBN cord-002542-f7l4ty2j 124 28 with with IN cord-002542-f7l4ty2j 124 29 an an DT cord-002542-f7l4ty2j 124 30 R9 R9 NNP cord-002542-f7l4ty2j 124 31 flow flow NN cord-002542-f7l4ty2j 124 32 cell cell NN cord-002542-f7l4ty2j 124 33 . . . cord-002542-f7l4ty2j 125 1 The the DT cord-002542-f7l4ty2j 125 2 MinKNOW minknow JJ cord-002542-f7l4ty2j 125 3 control control NN cord-002542-f7l4ty2j 125 4 software software NN cord-002542-f7l4ty2j 125 5 was be VBD cord-002542-f7l4ty2j 125 6 used use VBN cord-002542-f7l4ty2j 125 7 to to TO cord-002542-f7l4ty2j 125 8 select select VB cord-002542-f7l4ty2j 125 9 a a DT cord-002542-f7l4ty2j 125 10 48-hour 48-hour JJ cord-002542-f7l4ty2j 125 11 sequencing sequencing NN cord-002542-f7l4ty2j 125 12 protocol protocol NN cord-002542-f7l4ty2j 125 13 and and CC cord-002542-f7l4ty2j 125 14 was be VBD cord-002542-f7l4ty2j 125 15 allowed allow VBN cord-002542-f7l4ty2j 125 16 to to TO cord-002542-f7l4ty2j 125 17 proceed proceed VB cord-002542-f7l4ty2j 125 18 for for IN cord-002542-f7l4ty2j 125 19 at at RB cord-002542-f7l4ty2j 125 20 least least RBS cord-002542-f7l4ty2j 125 21 36 36 CD cord-002542-f7l4ty2j 125 22 hours hour NNS cord-002542-f7l4ty2j 125 23 , , , cord-002542-f7l4ty2j 125 24 until until IN cord-002542-f7l4ty2j 125 25 high high JJ cord-002542-f7l4ty2j 125 26 - - HYPH cord-002542-f7l4ty2j 125 27 quality quality NN cord-002542-f7l4ty2j 125 28 data datum NNS cord-002542-f7l4ty2j 125 29 accumulation accumulation NN cord-002542-f7l4ty2j 125 30 ceased cease VBD cord-002542-f7l4ty2j 125 31 . . . cord-002542-f7l4ty2j 126 1 Raw raw JJ cord-002542-f7l4ty2j 126 2 data datum NNS cord-002542-f7l4ty2j 126 3 was be VBD cord-002542-f7l4ty2j 126 4 uploaded upload VBN cord-002542-f7l4ty2j 126 5 automatically automatically RB cord-002542-f7l4ty2j 126 6 by by IN cord-002542-f7l4ty2j 126 7 Metrichor Metrichor NNP cord-002542-f7l4ty2j 126 8 software software NN cord-002542-f7l4ty2j 126 9 for for IN cord-002542-f7l4ty2j 126 10 cloudbased cloudbased JJ cord-002542-f7l4ty2j 126 11 base base NN cord-002542-f7l4ty2j 126 12 - - HYPH cord-002542-f7l4ty2j 126 13 calling call VBG cord-002542-f7l4ty2j 126 14 using use VBG cord-002542-f7l4ty2j 126 15 default default NN cord-002542-f7l4ty2j 126 16 settings setting NNS cord-002542-f7l4ty2j 126 17 and and CC cord-002542-f7l4ty2j 126 18 quality quality NN cord-002542-f7l4ty2j 126 19 filtering filter VBG cord-002542-f7l4ty2j 126 20 for for IN cord-002542-f7l4ty2j 126 21 2-dimensional 2-dimensional JJ cord-002542-f7l4ty2j 126 22 reads read NNS cord-002542-f7l4ty2j 126 23 . . . cord-002542-f7l4ty2j 127 1 Reads read NNS cord-002542-f7l4ty2j 127 2 were be VBD cord-002542-f7l4ty2j 127 3 extracted extract VBN cord-002542-f7l4ty2j 127 4 from from IN cord-002542-f7l4ty2j 127 5 HDF5 hdf5 JJ cord-002542-f7l4ty2j 127 6 format format NN cord-002542-f7l4ty2j 127 7 files file NNS cord-002542-f7l4ty2j 127 8 ( ( -LRB- cord-002542-f7l4ty2j 127 9 fast5 fast5 NN cord-002542-f7l4ty2j 127 10 ) ) -RRB- cord-002542-f7l4ty2j 127 11 using use VBG cord-002542-f7l4ty2j 127 12 poretools poretool NNS cord-002542-f7l4ty2j 127 13 [ [ -LRB- cord-002542-f7l4ty2j 127 14 48 48 CD cord-002542-f7l4ty2j 127 15 ] ] -RRB- cord-002542-f7l4ty2j 127 16 . . . cord-002542-f7l4ty2j 128 1 ONT ONT NNP cord-002542-f7l4ty2j 128 2 nanopore nanopore NNP cord-002542-f7l4ty2j 128 3 data datum NNS cord-002542-f7l4ty2j 128 4 processing processing NN cord-002542-f7l4ty2j 128 5 and and CC cord-002542-f7l4ty2j 128 6 alignment alignment NN cord-002542-f7l4ty2j 128 7 Full full JJ cord-002542-f7l4ty2j 128 8 - - HYPH cord-002542-f7l4ty2j 128 9 length length NN cord-002542-f7l4ty2j 128 10 ONT ONT NNP cord-002542-f7l4ty2j 128 11 reads read VBZ cord-002542-f7l4ty2j 128 12 were be VBD cord-002542-f7l4ty2j 128 13 mapped map VBN cord-002542-f7l4ty2j 128 14 to to IN cord-002542-f7l4ty2j 128 15 the the DT cord-002542-f7l4ty2j 128 16 Flock Flock NNP cord-002542-f7l4ty2j 128 17 House House NNP cord-002542-f7l4ty2j 128 18 virus virus NN cord-002542-f7l4ty2j 128 19 genome genome NN cord-002542-f7l4ty2j 128 20 using use VBG cord-002542-f7l4ty2j 128 21 the the DT cord-002542-f7l4ty2j 128 22 pacbio pacbio NNP cord-002542-f7l4ty2j 128 23 wrapper wrapper NN cord-002542-f7l4ty2j 128 24 from from IN cord-002542-f7l4ty2j 128 25 the the DT cord-002542-f7l4ty2j 128 26 BBMAP BBMAP NNP cord-002542-f7l4ty2j 128 27 v36 v36 NN cord-002542-f7l4ty2j 128 28 suite suite NN cord-002542-f7l4ty2j 128 29 ( ( -LRB- cord-002542-f7l4ty2j 128 30 command command NN cord-002542-f7l4ty2j 128 31 line line NN cord-002542-f7l4ty2j 128 32 parameters parameter NNS cord-002542-f7l4ty2j 128 33 : : : cord-002542-f7l4ty2j 128 34 fastareadlen fastareadlen NNP cord-002542-f7l4ty2j 128 35 = = SYM cord-002542-f7l4ty2j 128 36 6000 6000 CD cord-002542-f7l4ty2j 128 37 vslow vslow NN cord-002542-f7l4ty2j 128 38 = = SYM cord-002542-f7l4ty2j 128 39 t t NNP cord-002542-f7l4ty2j 128 40 maxindel maxindel NNP cord-002542-f7l4ty2j 128 41 = = SYM cord-002542-f7l4ty2j 128 42 3100 3100 CD cord-002542-f7l4ty2j 128 43 minid minid NNP cord-002542-f7l4ty2j 128 44 = = SYM cord-002542-f7l4ty2j 128 45 0.5 0.5 CD cord-002542-f7l4ty2j 128 46 local local JJ cord-002542-f7l4ty2j 128 47 = = SYM cord-002542-f7l4ty2j 128 48 f f NNP cord-002542-f7l4ty2j 128 49 ignorebadquality ignorebadquality NNP cord-002542-f7l4ty2j 128 50 = = SYM cord-002542-f7l4ty2j 128 51 t t NNP cord-002542-f7l4ty2j 128 52 usequality usequality NN cord-002542-f7l4ty2j 128 53 = = SYM cord-002542-f7l4ty2j 128 54 f f NNP cord-002542-f7l4ty2j 128 55 ) ) -RRB- cord-002542-f7l4ty2j 128 56 . . . cord-002542-f7l4ty2j 129 1 Alignment Alignment NNP cord-002542-f7l4ty2j 129 2 SAM SAM NNP cord-002542-f7l4ty2j 129 3 files file NNS cord-002542-f7l4ty2j 129 4 were be VBD cord-002542-f7l4ty2j 129 5 visualized visualize VBN cord-002542-f7l4ty2j 129 6 using use VBG cord-002542-f7l4ty2j 129 7 the the DT cord-002542-f7l4ty2j 129 8 Tablet Tablet NNP cord-002542-f7l4ty2j 129 9 sequence sequence NN cord-002542-f7l4ty2j 129 10 viewer viewer NN cord-002542-f7l4ty2j 129 11 [ [ -LRB- cord-002542-f7l4ty2j 129 12 49 49 CD cord-002542-f7l4ty2j 129 13 ] ] -RRB- cord-002542-f7l4ty2j 129 14 . . . cord-002542-f7l4ty2j 130 1 SAM SAM NNP cord-002542-f7l4ty2j 130 2 files file NNS cord-002542-f7l4ty2j 130 3 were be VBD cord-002542-f7l4ty2j 130 4 filtered filter VBN cord-002542-f7l4ty2j 130 5 to to TO cord-002542-f7l4ty2j 130 6 ensure ensure VB cord-002542-f7l4ty2j 130 7 that that IN cord-002542-f7l4ty2j 130 8 MinION MinION NNP cord-002542-f7l4ty2j 130 9 reads read VBZ cord-002542-f7l4ty2j 130 10 mapped map VBN cord-002542-f7l4ty2j 130 11 from from IN cord-002542-f7l4ty2j 130 12 the the DT cord-002542-f7l4ty2j 130 13 first first JJ cord-002542-f7l4ty2j 130 14 25 25 CD cord-002542-f7l4ty2j 130 15 nts nt NNS cord-002542-f7l4ty2j 130 16 to to IN cord-002542-f7l4ty2j 130 17 the the DT cord-002542-f7l4ty2j 130 18 final final JJ cord-002542-f7l4ty2j 130 19 25 25 CD cord-002542-f7l4ty2j 130 20 nts nt NNS cord-002542-f7l4ty2j 130 21 of of IN cord-002542-f7l4ty2j 130 22 the the DT cord-002542-f7l4ty2j 130 23 reference reference NN cord-002542-f7l4ty2j 130 24 genome genome NN cord-002542-f7l4ty2j 130 25 ( ( -LRB- cord-002542-f7l4ty2j 130 26 accounting account VBG cord-002542-f7l4ty2j 130 27 for for IN cord-002542-f7l4ty2j 130 28 deletions deletion NNS cord-002542-f7l4ty2j 130 29 and and CC cord-002542-f7l4ty2j 130 30 insertions insertion NNS cord-002542-f7l4ty2j 130 31 ) ) -RRB- cord-002542-f7l4ty2j 130 32 , , , cord-002542-f7l4ty2j 130 33 due due IN cord-002542-f7l4ty2j 130 34 to to IN cord-002542-f7l4ty2j 130 35 the the DT cord-002542-f7l4ty2j 130 36 presence presence NN cord-002542-f7l4ty2j 130 37 of of IN cord-002542-f7l4ty2j 130 38 truncated truncate VBN cord-002542-f7l4ty2j 130 39 nanopore nanopore NNP cord-002542-f7l4ty2j 130 40 reads read VBZ cord-002542-f7l4ty2j 130 41 and and CC cord-002542-f7l4ty2j 130 42 mis mis NN cord-002542-f7l4ty2j 130 43 - - NN cord-002542-f7l4ty2j 130 44 priming priming NN cord-002542-f7l4ty2j 130 45 during during IN cord-002542-f7l4ty2j 130 46 the the DT cord-002542-f7l4ty2j 130 47 cDNA cdna NN cord-002542-f7l4ty2j 130 48 PCR pcr NN cord-002542-f7l4ty2j 130 49 amplification amplification NN cord-002542-f7l4ty2j 130 50 steps step NNS cord-002542-f7l4ty2j 130 51 . . . cord-002542-f7l4ty2j 131 1 Errors error NNS cord-002542-f7l4ty2j 131 2 including include VBG cord-002542-f7l4ty2j 131 3 substitutions substitution NNS cord-002542-f7l4ty2j 131 4 , , , cord-002542-f7l4ty2j 131 5 insertions insertion NNS cord-002542-f7l4ty2j 131 6 and and CC cord-002542-f7l4ty2j 131 7 deletions deletion NNS cord-002542-f7l4ty2j 131 8 were be VBD cord-002542-f7l4ty2j 131 9 counted count VBN cord-002542-f7l4ty2j 131 10 using use VBG cord-002542-f7l4ty2j 131 11 the the DT cord-002542-f7l4ty2j 131 12 samtools samtool NNS cord-002542-f7l4ty2j 131 13 [ [ -LRB- cord-002542-f7l4ty2j 131 14 50 50 CD cord-002542-f7l4ty2j 131 15 ] ] -RRB- cord-002542-f7l4ty2j 131 16 mpileup mpileup NNP cord-002542-f7l4ty2j 131 17 command command NN cord-002542-f7l4ty2j 131 18 and and CC cord-002542-f7l4ty2j 131 19 error error NN cord-002542-f7l4ty2j 131 20 rates rate NNS cord-002542-f7l4ty2j 131 21 at at IN cord-002542-f7l4ty2j 131 22 each each DT cord-002542-f7l4ty2j 131 23 position position NN cord-002542-f7l4ty2j 131 24 were be VBD cord-002542-f7l4ty2j 131 25 calculated calculate VBN cord-002542-f7l4ty2j 131 26 by by IN cord-002542-f7l4ty2j 131 27 dividing divide VBG cord-002542-f7l4ty2j 131 28 this this DT cord-002542-f7l4ty2j 131 29 value value NN cord-002542-f7l4ty2j 131 30 by by IN cord-002542-f7l4ty2j 131 31 the the DT cord-002542-f7l4ty2j 131 32 read read NN cord-002542-f7l4ty2j 131 33 depth depth NN cord-002542-f7l4ty2j 131 34 at at IN cord-002542-f7l4ty2j 131 35 this this DT cord-002542-f7l4ty2j 131 36 position position NN cord-002542-f7l4ty2j 131 37 ( ( -LRB- cord-002542-f7l4ty2j 131 38 S5 S5 NNP cord-002542-f7l4ty2j 131 39 Fig Fig NNP cord-002542-f7l4ty2j 131 40 ) ) -RRB- cord-002542-f7l4ty2j 131 41 . . . cord-002542-f7l4ty2j 132 1 Insertion insertion NN cord-002542-f7l4ty2j 132 2 and and CC cord-002542-f7l4ty2j 132 3 deletion deletion NN cord-002542-f7l4ty2j 132 4 events event NNS cord-002542-f7l4ty2j 132 5 longer long RBR cord-002542-f7l4ty2j 132 6 that that IN cord-002542-f7l4ty2j 132 7 25 25 CD cord-002542-f7l4ty2j 132 8 nts nt NNS cord-002542-f7l4ty2j 132 9 were be VBD cord-002542-f7l4ty2j 132 10 extracted extract VBN cord-002542-f7l4ty2j 132 11 using use VBG cord-002542-f7l4ty2j 132 12 the the DT cord-002542-f7l4ty2j 132 13 CIGAR cigar NN cord-002542-f7l4ty2j 132 14 string string NN cord-002542-f7l4ty2j 132 15 of of IN cord-002542-f7l4ty2j 132 16 the the DT cord-002542-f7l4ty2j 132 17 SAM SAM NNP cord-002542-f7l4ty2j 132 18 files file NNS cord-002542-f7l4ty2j 132 19 using use VBG cord-002542-f7l4ty2j 132 20 simple simple JJ cord-002542-f7l4ty2j 132 21 in in IN cord-002542-f7l4ty2j 132 22 - - HYPH cord-002542-f7l4ty2j 132 23 house house NN cord-002542-f7l4ty2j 132 24 scripts script NNS cord-002542-f7l4ty2j 132 25 . . . cord-002542-f7l4ty2j 133 1 For for IN cord-002542-f7l4ty2j 133 2 recombination recombination NN cord-002542-f7l4ty2j 133 3 sites site NNS cord-002542-f7l4ty2j 133 4 containing contain VBG cord-002542-f7l4ty2j 133 5 ' ' `` cord-002542-f7l4ty2j 133 6 fuzz fuzz NN cord-002542-f7l4ty2j 133 7 ' ' '' cord-002542-f7l4ty2j 133 8 , , , cord-002542-f7l4ty2j 133 9 where where WRB cord-002542-f7l4ty2j 133 10 nucleotides nucleotide NNS cord-002542-f7l4ty2j 133 11 surrounding surround VBG cord-002542-f7l4ty2j 133 12 the the DT cord-002542-f7l4ty2j 133 13 putative putative JJ cord-002542-f7l4ty2j 133 14 recombination recombination NN cord-002542-f7l4ty2j 133 15 events event NNS cord-002542-f7l4ty2j 133 16 are be VBP cord-002542-f7l4ty2j 133 17 the the DT cord-002542-f7l4ty2j 133 18 same same JJ cord-002542-f7l4ty2j 133 19 for for IN cord-002542-f7l4ty2j 133 20 both both CC cord-002542-f7l4ty2j 133 21 the the DT cord-002542-f7l4ty2j 133 22 acceptor acceptor NN cord-002542-f7l4ty2j 133 23 and and CC cord-002542-f7l4ty2j 133 24 donor donor NN cord-002542-f7l4ty2j 133 25 sites site NNS cord-002542-f7l4ty2j 133 26 , , , cord-002542-f7l4ty2j 133 27 the the DT cord-002542-f7l4ty2j 133 28 recombination recombination NN cord-002542-f7l4ty2j 133 29 event event NN cord-002542-f7l4ty2j 133 30 was be VBD cord-002542-f7l4ty2j 133 31 reported report VBN cord-002542-f7l4ty2j 133 32 as as IN cord-002542-f7l4ty2j 133 33 occurring occur VBG cord-002542-f7l4ty2j 133 34 in in IN cord-002542-f7l4ty2j 133 35 the the DT cord-002542-f7l4ty2j 133 36 middle middle NN cord-002542-f7l4ty2j 133 37 of of IN cord-002542-f7l4ty2j 133 38 the the DT cord-002542-f7l4ty2j 133 39 ' ' `` cord-002542-f7l4ty2j 133 40 fuzzy fuzzy JJ cord-002542-f7l4ty2j 133 41 ' ' '' cord-002542-f7l4ty2j 133 42 region region NN cord-002542-f7l4ty2j 133 43 , , , cord-002542-f7l4ty2j 133 44 or or CC cord-002542-f7l4ty2j 133 45 at at IN cord-002542-f7l4ty2j 133 46 the the DT cord-002542-f7l4ty2j 133 47 5 5 CD cord-002542-f7l4ty2j 133 48 ' ' POS cord-002542-f7l4ty2j 133 49 side side NN cord-002542-f7l4ty2j 133 50 of of IN cord-002542-f7l4ty2j 133 51 the the DT cord-002542-f7l4ty2j 133 52 middle middle JJ cord-002542-f7l4ty2j 133 53 two two CD cord-002542-f7l4ty2j 133 54 nucleotides nucleotide NNS cord-002542-f7l4ty2j 133 55 in in IN cord-002542-f7l4ty2j 133 56 the the DT cord-002542-f7l4ty2j 133 57 orientation orientation NN cord-002542-f7l4ty2j 133 58 of of IN cord-002542-f7l4ty2j 133 59 the the DT cord-002542-f7l4ty2j 133 60 reference reference NN cord-002542-f7l4ty2j 133 61 if if IN cord-002542-f7l4ty2j 133 62 the the DT cord-002542-f7l4ty2j 133 63 fuzzy fuzzy JJ cord-002542-f7l4ty2j 133 64 site site NN cord-002542-f7l4ty2j 133 65 contained contain VBD cord-002542-f7l4ty2j 133 66 an an DT cord-002542-f7l4ty2j 133 67 even even JJ cord-002542-f7l4ty2j 133 68 number number NN cord-002542-f7l4ty2j 133 69 of of IN cord-002542-f7l4ty2j 133 70 residues residue NNS cord-002542-f7l4ty2j 133 71 . . . cord-002542-f7l4ty2j 134 1 This this DT cord-002542-f7l4ty2j 134 2 is be VBZ cord-002542-f7l4ty2j 134 3 the the DT cord-002542-f7l4ty2j 134 4 same same JJ cord-002542-f7l4ty2j 134 5 methodology methodology NN cord-002542-f7l4ty2j 134 6 as as IN cord-002542-f7l4ty2j 134 7 employed employ VBN cord-002542-f7l4ty2j 134 8 in in IN cord-002542-f7l4ty2j 134 9 the the DT cord-002542-f7l4ty2j 134 10 ViReMa virema NN cord-002542-f7l4ty2j 134 11 script script NN cord-002542-f7l4ty2j 134 12 [ [ -LRB- cord-002542-f7l4ty2j 134 13 32 32 CD cord-002542-f7l4ty2j 134 14 ] ] -RRB- cord-002542-f7l4ty2j 134 15 used use VBN cord-002542-f7l4ty2j 134 16 to to TO cord-002542-f7l4ty2j 134 17 map map VB cord-002542-f7l4ty2j 134 18 recombination recombination NN cord-002542-f7l4ty2j 134 19 event event NN cord-002542-f7l4ty2j 134 20 in in IN cord-002542-f7l4ty2j 134 21 the the DT cord-002542-f7l4ty2j 134 22 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 134 23 data datum NNS cord-002542-f7l4ty2j 134 24 . . . cord-002542-f7l4ty2j 135 1 Insertion insertion NN cord-002542-f7l4ty2j 135 2 events event NNS cord-002542-f7l4ty2j 135 3 and and CC cord-002542-f7l4ty2j 135 4 soft soft JJ cord-002542-f7l4ty2j 135 5 - - HYPH cord-002542-f7l4ty2j 135 6 pads pad NNS cord-002542-f7l4ty2j 135 7 longer long RBR cord-002542-f7l4ty2j 135 8 than than IN cord-002542-f7l4ty2j 135 9 100 100 CD cord-002542-f7l4ty2j 135 10 nts nt NNS cord-002542-f7l4ty2j 135 11 were be VBD cord-002542-f7l4ty2j 135 12 extracted extract VBN cord-002542-f7l4ty2j 135 13 and and CC cord-002542-f7l4ty2j 135 14 their -PRON- PRP$ cord-002542-f7l4ty2j 135 15 nucleotide nucleotide JJ cord-002542-f7l4ty2j 135 16 sequence sequence NN cord-002542-f7l4ty2j 135 17 was be VBD cord-002542-f7l4ty2j 135 18 analyzed analyze VBN cord-002542-f7l4ty2j 135 19 using use VBG cord-002542-f7l4ty2j 135 20 an an DT cord-002542-f7l4ty2j 135 21 online online JJ cord-002542-f7l4ty2j 135 22 BLASTn BLASTn NNS cord-002542-f7l4ty2j 135 23 search search NN cord-002542-f7l4ty2j 135 24 to to TO cord-002542-f7l4ty2j 135 25 determine determine VB cord-002542-f7l4ty2j 135 26 their -PRON- PRP$ cord-002542-f7l4ty2j 135 27 identity identity NN cord-002542-f7l4ty2j 135 28 . . . cord-002542-f7l4ty2j 136 1 To to TO cord-002542-f7l4ty2j 136 2 annotate annotate VB cord-002542-f7l4ty2j 136 3 the the DT cord-002542-f7l4ty2j 136 4 defective defective JJ cord-002542-f7l4ty2j 136 5 genomes genome NNS cord-002542-f7l4ty2j 136 6 detected detect VBN cord-002542-f7l4ty2j 136 7 by by IN cord-002542-f7l4ty2j 136 8 MinION MinION VBG cord-002542-f7l4ty2j 136 9 nanopore nanopore JJ cord-002542-f7l4ty2j 136 10 sequencing sequencing NN cord-002542-f7l4ty2j 136 11 or or CC cord-002542-f7l4ty2j 136 12 recombination recombination NN cord-002542-f7l4ty2j 136 13 events event NNS cord-002542-f7l4ty2j 136 14 detected detect VBN cord-002542-f7l4ty2j 136 15 by by IN cord-002542-f7l4ty2j 136 16 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 136 17 , , , cord-002542-f7l4ty2j 136 18 we -PRON- PRP cord-002542-f7l4ty2j 136 19 use use VBP cord-002542-f7l4ty2j 136 20 underscores underscore VBZ cord-002542-f7l4ty2j 136 21 ' ' `` cord-002542-f7l4ty2j 136 22 _ _ NN cord-002542-f7l4ty2j 136 23 ' ' '' cord-002542-f7l4ty2j 136 24 to to TO cord-002542-f7l4ty2j 136 25 denote denote VB cord-002542-f7l4ty2j 136 26 continued continued JJ cord-002542-f7l4ty2j 136 27 mapping mapping NN cord-002542-f7l4ty2j 136 28 , , , cord-002542-f7l4ty2j 136 29 and and CC cord-002542-f7l4ty2j 136 30 carets caret NNS cord-002542-f7l4ty2j 136 31 ' ' '' cord-002542-f7l4ty2j 136 32 ^ ^ SYM cord-002542-f7l4ty2j 136 33 ' ' '' cord-002542-f7l4ty2j 136 34 to to TO cord-002542-f7l4ty2j 136 35 denote denote VB cord-002542-f7l4ty2j 136 36 a a DT cord-002542-f7l4ty2j 136 37 recombination recombination NN cord-002542-f7l4ty2j 136 38 events event NNS cord-002542-f7l4ty2j 136 39 . . . cord-002542-f7l4ty2j 137 1 For for IN cord-002542-f7l4ty2j 137 2 example example NN cord-002542-f7l4ty2j 137 3 , , , cord-002542-f7l4ty2j 137 4 " " '' cord-002542-f7l4ty2j 137 5 1_317 1_317 CD cord-002542-f7l4ty2j 137 6 ^ ^ : cord-002542-f7l4ty2j 137 7 1091_1242 1091_1242 CD cord-002542-f7l4ty2j 137 8 ^ ^ : cord-002542-f7l4ty2j 137 9 2301_3107 2301_3107 CD cord-002542-f7l4ty2j 137 10 " " '' cord-002542-f7l4ty2j 137 11 indicates indicate VBZ cord-002542-f7l4ty2j 137 12 an an DT cord-002542-f7l4ty2j 137 13 authentic authentic JJ cord-002542-f7l4ty2j 137 14 mapping mapping NN cord-002542-f7l4ty2j 137 15 from from IN cord-002542-f7l4ty2j 137 16 nt nt RB cord-002542-f7l4ty2j 137 17 1 1 CD cord-002542-f7l4ty2j 137 18 to to IN cord-002542-f7l4ty2j 137 19 317 317 CD cord-002542-f7l4ty2j 137 20 , , , cord-002542-f7l4ty2j 137 21 then then RB cord-002542-f7l4ty2j 137 22 a a DT cord-002542-f7l4ty2j 137 23 deletion deletion NN cord-002542-f7l4ty2j 137 24 event event NN cord-002542-f7l4ty2j 137 25 removing remove VBG cord-002542-f7l4ty2j 137 26 nts nts NNPS cord-002542-f7l4ty2j 137 27 318 318 CD cord-002542-f7l4ty2j 137 28 through through IN cord-002542-f7l4ty2j 137 29 1090 1090 CD cord-002542-f7l4ty2j 137 30 , , , cord-002542-f7l4ty2j 137 31 then then RB cord-002542-f7l4ty2j 137 32 another another DT cord-002542-f7l4ty2j 137 33 authentic authentic JJ cord-002542-f7l4ty2j 137 34 mapping mapping NN cord-002542-f7l4ty2j 137 35 from from IN cord-002542-f7l4ty2j 137 36 1091 1091 CD cord-002542-f7l4ty2j 137 37 to to IN cord-002542-f7l4ty2j 137 38 1242 1242 CD cord-002542-f7l4ty2j 137 39 , , , cord-002542-f7l4ty2j 137 40 followed follow VBN cord-002542-f7l4ty2j 137 41 by by IN cord-002542-f7l4ty2j 137 42 another another DT cord-002542-f7l4ty2j 137 43 deletion deletion NN cord-002542-f7l4ty2j 137 44 removing remove VBG cord-002542-f7l4ty2j 137 45 nts nts NNPS cord-002542-f7l4ty2j 137 46 1243 1243 CD cord-002542-f7l4ty2j 137 47 through through IN cord-002542-f7l4ty2j 137 48 2300 2300 CD cord-002542-f7l4ty2j 137 49 , , , cord-002542-f7l4ty2j 137 50 and and CC cord-002542-f7l4ty2j 137 51 finally finally RB cord-002542-f7l4ty2j 137 52 an an DT cord-002542-f7l4ty2j 137 53 authentic authentic JJ cord-002542-f7l4ty2j 137 54 mapping mapping NN cord-002542-f7l4ty2j 137 55 from from IN cord-002542-f7l4ty2j 137 56 nt nt RB cord-002542-f7l4ty2j 137 57 2301 2301 CD cord-002542-f7l4ty2j 137 58 to to IN cord-002542-f7l4ty2j 137 59 3107 3107 CD cord-002542-f7l4ty2j 137 60 . . . cord-002542-f7l4ty2j 138 1 The the DT cord-002542-f7l4ty2j 138 2 Shannon Shannon NNP cord-002542-f7l4ty2j 138 3 Entropy Entropy NNP cord-002542-f7l4ty2j 138 4 Index Index NNP cord-002542-f7l4ty2j 138 5 is be VBZ cord-002542-f7l4ty2j 138 6 given give VBN cord-002542-f7l4ty2j 138 7 by by IN cord-002542-f7l4ty2j 138 8 : : : cord-002542-f7l4ty2j 139 1 HðXÞ HðXÞ NNP cord-002542-f7l4ty2j 139 2 ¼ ¼ NNP cord-002542-f7l4ty2j 139 3 À à NN cord-002542-f7l4ty2j 139 4 P p NN cord-002542-f7l4ty2j 139 5 NÀ NÀ NNP cord-002542-f7l4ty2j 139 6 1 1 CD cord-002542-f7l4ty2j 139 7 i¼0 i¼0 NN cord-002542-f7l4ty2j 140 1 p p NNP cord-002542-f7l4ty2j 140 2 i i PRP cord-002542-f7l4ty2j 140 3 ln ln NN cord-002542-f7l4ty2j 140 4 p p NN cord-002542-f7l4ty2j 140 5 i i PRP cord-002542-f7l4ty2j 140 6 For for IN cord-002542-f7l4ty2j 140 7 the the DT cord-002542-f7l4ty2j 140 8 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 140 9 data datum NNS cord-002542-f7l4ty2j 141 1 , , , cord-002542-f7l4ty2j 141 2 each each DT cord-002542-f7l4ty2j 141 3 recombination recombination NN cord-002542-f7l4ty2j 141 4 event event NN cord-002542-f7l4ty2j 141 5 is be VBZ cord-002542-f7l4ty2j 141 6 treated treat VBN cord-002542-f7l4ty2j 141 7 as as IN cord-002542-f7l4ty2j 141 8 independent independent JJ cord-002542-f7l4ty2j 141 9 with with IN cord-002542-f7l4ty2j 141 10 its -PRON- PRP$ cord-002542-f7l4ty2j 141 11 probability probability NN cord-002542-f7l4ty2j 141 12 determined determine VBN cord-002542-f7l4ty2j 141 13 by by IN cord-002542-f7l4ty2j 141 14 dividing divide VBG cord-002542-f7l4ty2j 141 15 the the DT cord-002542-f7l4ty2j 141 16 number number NN cord-002542-f7l4ty2j 141 17 of of IN cord-002542-f7l4ty2j 141 18 reads read NNS cord-002542-f7l4ty2j 141 19 mapping mapping NN cord-002542-f7l4ty2j 141 20 to to IN cord-002542-f7l4ty2j 141 21 the the DT cord-002542-f7l4ty2j 141 22 present present JJ cord-002542-f7l4ty2j 141 23 recombination recombination NN cord-002542-f7l4ty2j 141 24 event event NN cord-002542-f7l4ty2j 141 25 divided divide VBN cord-002542-f7l4ty2j 141 26 by by IN cord-002542-f7l4ty2j 141 27 the the DT cord-002542-f7l4ty2j 141 28 average average JJ cord-002542-f7l4ty2j 141 29 coverage coverage NN cord-002542-f7l4ty2j 141 30 over over IN cord-002542-f7l4ty2j 141 31 the the DT cord-002542-f7l4ty2j 141 32 whole whole JJ cord-002542-f7l4ty2j 141 33 viral viral JJ cord-002542-f7l4ty2j 141 34 RNA RNA NNP cord-002542-f7l4ty2j 141 35 . . . cord-002542-f7l4ty2j 142 1 For for IN cord-002542-f7l4ty2j 142 2 the the DT cord-002542-f7l4ty2j 142 3 MinION MinION NNP cord-002542-f7l4ty2j 142 4 data datum NNS cord-002542-f7l4ty2j 142 5 , , , cord-002542-f7l4ty2j 142 6 each each DT cord-002542-f7l4ty2j 142 7 individual individual JJ cord-002542-f7l4ty2j 142 8 read read VBD cord-002542-f7l4ty2j 142 9 mapping mapping NN cord-002542-f7l4ty2j 142 10 is be VBZ cord-002542-f7l4ty2j 142 11 treated treat VBN cord-002542-f7l4ty2j 142 12 as as IN cord-002542-f7l4ty2j 142 13 an an DT cord-002542-f7l4ty2j 142 14 individual individual JJ cord-002542-f7l4ty2j 142 15 event event NN cord-002542-f7l4ty2j 142 16 with with IN cord-002542-f7l4ty2j 142 17 the the DT cord-002542-f7l4ty2j 142 18 frequency frequency NN cord-002542-f7l4ty2j 142 19 determined determine VBN cord-002542-f7l4ty2j 142 20 by by IN cord-002542-f7l4ty2j 142 21 dividing divide VBG cord-002542-f7l4ty2j 142 22 the the DT cord-002542-f7l4ty2j 142 23 number number NN cord-002542-f7l4ty2j 142 24 of of IN cord-002542-f7l4ty2j 142 25 identically identically RB cord-002542-f7l4ty2j 142 26 mapping mapping NN cord-002542-f7l4ty2j 142 27 reads read NNS cord-002542-f7l4ty2j 142 28 divided divide VBN cord-002542-f7l4ty2j 142 29 by by IN cord-002542-f7l4ty2j 142 30 total total JJ cord-002542-f7l4ty2j 142 31 mapped map VBN cord-002542-f7l4ty2j 142 32 reads read NNS cord-002542-f7l4ty2j 142 33 . . . cord-002542-f7l4ty2j 143 1 Tissue tissue NN cord-002542-f7l4ty2j 143 2 culture culture NN cord-002542-f7l4ty2j 143 3 infective infective JJ cord-002542-f7l4ty2j 143 4 dose dose NN cord-002542-f7l4ty2j 143 5 50 50 CD cord-002542-f7l4ty2j 144 1 ( ( -LRB- cord-002542-f7l4ty2j 144 2 TCID50 TCID50 NNP cord-002542-f7l4ty2j 144 3 ) ) -RRB- cord-002542-f7l4ty2j 144 4 analyses analysis NNS cord-002542-f7l4ty2j 144 5 of of IN cord-002542-f7l4ty2j 144 6 the the DT cord-002542-f7l4ty2j 144 7 supernatants supernatant NNS cord-002542-f7l4ty2j 144 8 from from IN cord-002542-f7l4ty2j 144 9 each each DT cord-002542-f7l4ty2j 144 10 passage passage NN cord-002542-f7l4ty2j 144 11 were be VBD cord-002542-f7l4ty2j 144 12 performed perform VBN cord-002542-f7l4ty2j 144 13 using use VBG cord-002542-f7l4ty2j 144 14 standard standard JJ cord-002542-f7l4ty2j 144 15 protocols protocol NNS cord-002542-f7l4ty2j 144 16 [ [ -LRB- cord-002542-f7l4ty2j 144 17 51 51 CD cord-002542-f7l4ty2j 144 18 ] ] -RRB- cord-002542-f7l4ty2j 144 19 . . . cord-002542-f7l4ty2j 145 1 For for IN cord-002542-f7l4ty2j 145 2 purified purify VBN cord-002542-f7l4ty2j 145 3 particles particle NNS cord-002542-f7l4ty2j 145 4 of of IN cord-002542-f7l4ty2j 145 5 each each DT cord-002542-f7l4ty2j 145 6 passage passage NN cord-002542-f7l4ty2j 145 7 TCID50 TCID50 NNP cord-002542-f7l4ty2j 145 8 was be VBD cord-002542-f7l4ty2j 145 9 calculated calculate VBN cord-002542-f7l4ty2j 145 10 with with IN cord-002542-f7l4ty2j 145 11 slight slight JJ cord-002542-f7l4ty2j 145 12 modifications modification NNS cord-002542-f7l4ty2j 145 13 . . . cord-002542-f7l4ty2j 146 1 Specifically specifically RB cord-002542-f7l4ty2j 146 2 , , , cord-002542-f7l4ty2j 146 3 1 1 CD cord-002542-f7l4ty2j 146 4 x x SYM cord-002542-f7l4ty2j 146 5 10 10 CD cord-002542-f7l4ty2j 146 6 5 5 CD cord-002542-f7l4ty2j 146 7 cells cell NNS cord-002542-f7l4ty2j 146 8 ( ( -LRB- cord-002542-f7l4ty2j 146 9 S2 s2 NN cord-002542-f7l4ty2j 146 10 ) ) -RRB- cord-002542-f7l4ty2j 146 11 per per FW cord-002542-f7l4ty2j 146 12 well well RB cord-002542-f7l4ty2j 146 13 were be VBD cord-002542-f7l4ty2j 146 14 plated plate VBN cord-002542-f7l4ty2j 146 15 in in IN cord-002542-f7l4ty2j 146 16 96 96 CD cord-002542-f7l4ty2j 146 17 well well JJ cord-002542-f7l4ty2j 146 18 format format NN cord-002542-f7l4ty2j 146 19 . . . cord-002542-f7l4ty2j 147 1 Virus virus NN cord-002542-f7l4ty2j 147 2 samples sample NNS cord-002542-f7l4ty2j 147 3 were be VBD cord-002542-f7l4ty2j 147 4 quantified quantify VBN cord-002542-f7l4ty2j 147 5 by by IN cord-002542-f7l4ty2j 147 6 measuring measure VBG cord-002542-f7l4ty2j 147 7 the the DT cord-002542-f7l4ty2j 147 8 OD OD NNP cord-002542-f7l4ty2j 147 9 260 260 CD cord-002542-f7l4ty2j 147 10 nm nm NN cord-002542-f7l4ty2j 147 11 . . . cord-002542-f7l4ty2j 148 1 An an DT cord-002542-f7l4ty2j 148 2 OD OD NNP cord-002542-f7l4ty2j 148 3 of of IN cord-002542-f7l4ty2j 148 4 4.15 4.15 CD cord-002542-f7l4ty2j 148 5 corresponds correspond VBZ cord-002542-f7l4ty2j 148 6 to to IN cord-002542-f7l4ty2j 148 7 1 1 CD cord-002542-f7l4ty2j 148 8 mg mg NN cord-002542-f7l4ty2j 148 9 virus virus NN cord-002542-f7l4ty2j 148 10 [ [ -LRB- cord-002542-f7l4ty2j 148 11 52 52 CD cord-002542-f7l4ty2j 148 12 ] ] -RRB- cord-002542-f7l4ty2j 148 13 , , , cord-002542-f7l4ty2j 148 14 which which WDT cord-002542-f7l4ty2j 148 15 in in IN cord-002542-f7l4ty2j 148 16 turn turn NN cord-002542-f7l4ty2j 148 17 corresponds correspond VBZ cord-002542-f7l4ty2j 148 18 to to IN cord-002542-f7l4ty2j 148 19 6.4 6.4 CD cord-002542-f7l4ty2j 148 20 x x SYM cord-002542-f7l4ty2j 148 21 10 10 CD cord-002542-f7l4ty2j 148 22 13 13 CD cord-002542-f7l4ty2j 148 23 virus virus NN cord-002542-f7l4ty2j 148 24 particles particle NNS cord-002542-f7l4ty2j 148 25 assuming assume VBG cord-002542-f7l4ty2j 148 26 a a DT cord-002542-f7l4ty2j 148 27 virion virion NN cord-002542-f7l4ty2j 148 28 mass mass NN cord-002542-f7l4ty2j 148 29 of of IN cord-002542-f7l4ty2j 148 30 9.4MDa 9.4mda CD cord-002542-f7l4ty2j 148 31 [ [ -LRB- cord-002542-f7l4ty2j 148 32 53 53 CD cord-002542-f7l4ty2j 148 33 ] ] -RRB- cord-002542-f7l4ty2j 148 34 . . . cord-002542-f7l4ty2j 149 1 Purified purify VBN cord-002542-f7l4ty2j 149 2 virus virus NN cord-002542-f7l4ty2j 149 3 samples sample NNS cord-002542-f7l4ty2j 149 4 were be VBD cord-002542-f7l4ty2j 149 5 diluted dilute VBN cord-002542-f7l4ty2j 149 6 to to IN cord-002542-f7l4ty2j 149 7 a a DT cord-002542-f7l4ty2j 149 8 starting start VBG cord-002542-f7l4ty2j 149 9 concentration concentration NN cord-002542-f7l4ty2j 149 10 of of IN cord-002542-f7l4ty2j 149 11 47ng 47ng NN cord-002542-f7l4ty2j 149 12 / / SYM cord-002542-f7l4ty2j 149 13 μL μL NNP cord-002542-f7l4ty2j 149 14 , , , cord-002542-f7l4ty2j 149 15 which which WDT cord-002542-f7l4ty2j 149 16 corresponds correspond VBZ cord-002542-f7l4ty2j 149 17 to to IN cord-002542-f7l4ty2j 149 18 3 3 CD cord-002542-f7l4ty2j 149 19 x x SYM cord-002542-f7l4ty2j 149 20 10 10 CD cord-002542-f7l4ty2j 149 21 10 10 CD cord-002542-f7l4ty2j 149 22 virus virus NN cord-002542-f7l4ty2j 149 23 particles particle NNS cord-002542-f7l4ty2j 149 24 per per IN cord-002542-f7l4ty2j 149 25 10μL. 10μl. CD cord-002542-f7l4ty2j 149 26 These these DT cord-002542-f7l4ty2j 149 27 quantities quantity NNS cord-002542-f7l4ty2j 149 28 were be VBD cord-002542-f7l4ty2j 149 29 chosen choose VBN cord-002542-f7l4ty2j 149 30 as as IN cord-002542-f7l4ty2j 149 31 particle particle NN cord-002542-f7l4ty2j 149 32 - - HYPH cord-002542-f7l4ty2j 149 33 to to IN cord-002542-f7l4ty2j 149 34 - - HYPH cord-002542-f7l4ty2j 149 35 PFU pfu NN cord-002542-f7l4ty2j 149 36 ratios ratio NNS cord-002542-f7l4ty2j 149 37 for for IN cord-002542-f7l4ty2j 149 38 rescued rescue VBN cord-002542-f7l4ty2j 149 39 FHV FHV NNP cord-002542-f7l4ty2j 149 40 has have VBZ cord-002542-f7l4ty2j 149 41 previously previously RB cord-002542-f7l4ty2j 149 42 been be VBN cord-002542-f7l4ty2j 149 43 reported report VBN cord-002542-f7l4ty2j 149 44 to to TO cord-002542-f7l4ty2j 149 45 be be VB cord-002542-f7l4ty2j 149 46 300 300 CD cord-002542-f7l4ty2j 149 47 - - SYM cord-002542-f7l4ty2j 149 48 400 400 CD cord-002542-f7l4ty2j 149 49 particles particle NNS cord-002542-f7l4ty2j 149 50 [ [ -LRB- cord-002542-f7l4ty2j 149 51 26 26 CD cord-002542-f7l4ty2j 149 52 , , , cord-002542-f7l4ty2j 149 53 52 52 CD cord-002542-f7l4ty2j 149 54 ] ] -RRB- cord-002542-f7l4ty2j 149 55 . . . cord-002542-f7l4ty2j 150 1 Therefore therefore RB cord-002542-f7l4ty2j 150 2 3 3 CD cord-002542-f7l4ty2j 150 3 x x SYM cord-002542-f7l4ty2j 150 4 10 10 CD cord-002542-f7l4ty2j 150 5 10 10 CD cord-002542-f7l4ty2j 150 6 particles particle NNS cord-002542-f7l4ty2j 150 7 per per IN cord-002542-f7l4ty2j 150 8 10 10 CD cord-002542-f7l4ty2j 150 9 5 5 CD cord-002542-f7l4ty2j 150 10 cells cell NNS cord-002542-f7l4ty2j 150 11 corresponds correspond VBZ cord-002542-f7l4ty2j 150 12 to to IN cord-002542-f7l4ty2j 150 13 approximately approximately RB cord-002542-f7l4ty2j 150 14 1000 1000 CD cord-002542-f7l4ty2j 150 15 PFUs pfus NN cord-002542-f7l4ty2j 150 16 per per IN cord-002542-f7l4ty2j 150 17 cell cell NN cord-002542-f7l4ty2j 150 18 . . . cord-002542-f7l4ty2j 151 1 Eight eight CD cord-002542-f7l4ty2j 151 2 serial serial JJ cord-002542-f7l4ty2j 151 3 10-fold 10-fold JJ cord-002542-f7l4ty2j 151 4 dilutions dilution NNS cord-002542-f7l4ty2j 151 5 were be VBD cord-002542-f7l4ty2j 151 6 subsequently subsequently RB cord-002542-f7l4ty2j 151 7 made make VBN cord-002542-f7l4ty2j 151 8 and and CC cord-002542-f7l4ty2j 151 9 added add VBN cord-002542-f7l4ty2j 151 10 to to IN cord-002542-f7l4ty2j 151 11 each each DT cord-002542-f7l4ty2j 151 12 column column NN cord-002542-f7l4ty2j 151 13 of of IN cord-002542-f7l4ty2j 151 14 the the DT cord-002542-f7l4ty2j 151 15 96-well 96-well CD cord-002542-f7l4ty2j 151 16 plate plate NN cord-002542-f7l4ty2j 151 17 ( ( -LRB- cord-002542-f7l4ty2j 151 18 8 8 CD cord-002542-f7l4ty2j 151 19 replicate replicate VB cord-002542-f7l4ty2j 151 20 wells well NNS cord-002542-f7l4ty2j 151 21 per per IN cord-002542-f7l4ty2j 151 22 dilution dilution NN cord-002542-f7l4ty2j 151 23 ) ) -RRB- cord-002542-f7l4ty2j 151 24 , , , cord-002542-f7l4ty2j 151 25 as as IN cord-002542-f7l4ty2j 151 26 per per IN cord-002542-f7l4ty2j 151 27 standard standard JJ cord-002542-f7l4ty2j 151 28 TCID50 tcid50 CD cord-002542-f7l4ty2j 151 29 protocols protocol NNS cord-002542-f7l4ty2j 151 30 . . . cord-002542-f7l4ty2j 152 1 Virus virus NN cord-002542-f7l4ty2j 152 2 was be VBD cord-002542-f7l4ty2j 152 3 allowed allow VBN cord-002542-f7l4ty2j 152 4 to to TO cord-002542-f7l4ty2j 152 5 grow grow VB cord-002542-f7l4ty2j 152 6 for for IN cord-002542-f7l4ty2j 152 7 4 4 CD cord-002542-f7l4ty2j 152 8 days day NNS cord-002542-f7l4ty2j 152 9 after after IN cord-002542-f7l4ty2j 152 10 which which WDT cord-002542-f7l4ty2j 152 11 the the DT cord-002542-f7l4ty2j 152 12 number number NN cord-002542-f7l4ty2j 152 13 of of IN cord-002542-f7l4ty2j 152 14 positive positive JJ cord-002542-f7l4ty2j 152 15 wells well NNS cord-002542-f7l4ty2j 152 16 exhibiting exhibit VBG cord-002542-f7l4ty2j 152 17 cytopathic cytopathic JJ cord-002542-f7l4ty2j 152 18 effect effect NN cord-002542-f7l4ty2j 152 19 ( ( -LRB- cord-002542-f7l4ty2j 152 20 CPE CPE NNP cord-002542-f7l4ty2j 152 21 ) ) -RRB- cord-002542-f7l4ty2j 152 22 were be VBD cord-002542-f7l4ty2j 152 23 counted count VBN cord-002542-f7l4ty2j 152 24 . . . cord-002542-f7l4ty2j 153 1 The the DT cord-002542-f7l4ty2j 153 2 TCID50 TCID50 NNP cord-002542-f7l4ty2j 153 3 values value NNS cord-002542-f7l4ty2j 153 4 and and CC cord-002542-f7l4ty2j 153 5 effective effective JJ cord-002542-f7l4ty2j 153 6 MOI MOI NNP cord-002542-f7l4ty2j 153 7 were be VBD cord-002542-f7l4ty2j 153 8 calculated calculate VBN cord-002542-f7l4ty2j 153 9 using use VBG cord-002542-f7l4ty2j 153 10 the the DT cord-002542-f7l4ty2j 153 11 Reed Reed NNP cord-002542-f7l4ty2j 153 12 and and CC cord-002542-f7l4ty2j 153 13 Muench Muench NNP cord-002542-f7l4ty2j 153 14 Calculator Calculator NNP cord-002542-f7l4ty2j 153 15 [ [ -LRB- cord-002542-f7l4ty2j 153 16 51 51 CD cord-002542-f7l4ty2j 153 17 ] ] -RRB- cord-002542-f7l4ty2j 153 18 . . . cord-002542-f7l4ty2j 154 1 We -PRON- PRP cord-002542-f7l4ty2j 154 2 further further RB cord-002542-f7l4ty2j 154 3 counted count VBD cord-002542-f7l4ty2j 154 4 the the DT cord-002542-f7l4ty2j 154 5 total total JJ cord-002542-f7l4ty2j 154 6 number number NN cord-002542-f7l4ty2j 154 7 of of IN cord-002542-f7l4ty2j 154 8 cells cell NNS cord-002542-f7l4ty2j 154 9 that that WDT cord-002542-f7l4ty2j 154 10 were be VBD cord-002542-f7l4ty2j 154 11 present present JJ cord-002542-f7l4ty2j 154 12 in in IN cord-002542-f7l4ty2j 154 13 each each DT cord-002542-f7l4ty2j 154 14 well well RB cord-002542-f7l4ty2j 154 15 after after IN cord-002542-f7l4ty2j 154 16 infection infection NN cord-002542-f7l4ty2j 154 17 using use VBG cord-002542-f7l4ty2j 154 18 a a DT cord-002542-f7l4ty2j 154 19 Guava Guava NNP cord-002542-f7l4ty2j 154 20 easyCyte easycyte JJ cord-002542-f7l4ty2j 154 21 HT HT NNP cord-002542-f7l4ty2j 154 22 ( ( -LRB- cord-002542-f7l4ty2j 154 23 Millipore Millipore NNP cord-002542-f7l4ty2j 154 24 ) ) -RRB- cord-002542-f7l4ty2j 154 25 flow flow VBP cord-002542-f7l4ty2j 154 26 cytometer cytometer NN cord-002542-f7l4ty2j 154 27 to to TO cord-002542-f7l4ty2j 154 28 provide provide VB cord-002542-f7l4ty2j 154 29 us -PRON- PRP cord-002542-f7l4ty2j 154 30 with with IN cord-002542-f7l4ty2j 154 31 quantifiable quantifiable JJ cord-002542-f7l4ty2j 154 32 amount amount NN cord-002542-f7l4ty2j 154 33 of of IN cord-002542-f7l4ty2j 154 34 cell cell NN cord-002542-f7l4ty2j 154 35 death death NN cord-002542-f7l4ty2j 154 36 . . . cord-002542-f7l4ty2j 155 1 50μL 50μl CD cord-002542-f7l4ty2j 155 2 from from IN cord-002542-f7l4ty2j 155 3 each each DT cord-002542-f7l4ty2j 155 4 well well NN cord-002542-f7l4ty2j 155 5 was be VBD cord-002542-f7l4ty2j 155 6 diluted dilute VBN cord-002542-f7l4ty2j 155 7 in in IN cord-002542-f7l4ty2j 155 8 150μL 150μl CD cord-002542-f7l4ty2j 155 9 PBS PBS NNP cord-002542-f7l4ty2j 155 10 and and CC cord-002542-f7l4ty2j 155 11 injected inject VBD cord-002542-f7l4ty2j 155 12 using use VBG cord-002542-f7l4ty2j 155 13 manufactures manufacture NNS cord-002542-f7l4ty2j 155 14 ' ' POS cord-002542-f7l4ty2j 155 15 protocols protocol NNS cord-002542-f7l4ty2j 155 16 . . . cord-002542-f7l4ty2j 156 1 The the DT cord-002542-f7l4ty2j 156 2 InCyt InCyt NNP cord-002542-f7l4ty2j 156 3 v3.1 v3.1 NN cord-002542-f7l4ty2j 156 4 software software NN cord-002542-f7l4ty2j 156 5 was be VBD cord-002542-f7l4ty2j 156 6 used use VBN cord-002542-f7l4ty2j 156 7 to to TO cord-002542-f7l4ty2j 156 8 collect collect VB cord-002542-f7l4ty2j 156 9 data datum NNS cord-002542-f7l4ty2j 156 10 with with IN cord-002542-f7l4ty2j 156 11 the the DT cord-002542-f7l4ty2j 156 12 following follow VBG cord-002542-f7l4ty2j 156 13 parameters parameter NNS cord-002542-f7l4ty2j 156 14 : : : cord-002542-f7l4ty2j 156 15 collection collection NN cord-002542-f7l4ty2j 156 16 time time NN cord-002542-f7l4ty2j 156 17 : : : cord-002542-f7l4ty2j 156 18 30sec 30sec JJ cord-002542-f7l4ty2j 156 19 ; ; : cord-002542-f7l4ty2j 156 20 flow flow NN cord-002542-f7l4ty2j 156 21 rate rate NN cord-002542-f7l4ty2j 156 22 : : : cord-002542-f7l4ty2j 156 23 0.59μL 0.59μl CD cord-002542-f7l4ty2j 156 24 / / SYM cord-002542-f7l4ty2j 156 25 sec sec NNP cord-002542-f7l4ty2j 156 26 ; ; : cord-002542-f7l4ty2j 156 27 FSC FSC NNP cord-002542-f7l4ty2j 156 28 : : : cord-002542-f7l4ty2j 156 29 16 16 CD cord-002542-f7l4ty2j 157 1 ; ; : cord-002542-f7l4ty2j 157 2 SSC SSC NNP cord-002542-f7l4ty2j 157 3 : : : cord-002542-f7l4ty2j 157 4 25 25 CD cord-002542-f7l4ty2j 157 5 ; ; , cord-002542-f7l4ty2j 157 6 threshold threshold NN cord-002542-f7l4ty2j 157 7 : : : cord-002542-f7l4ty2j 157 8 0 0 NFP cord-002542-f7l4ty2j 157 9 . . . cord-002542-f7l4ty2j 158 1 The the DT cord-002542-f7l4ty2j 158 2 region region NN cord-002542-f7l4ty2j 158 3 used use VBD cord-002542-f7l4ty2j 158 4 to to TO cord-002542-f7l4ty2j 158 5 determine determine VB cord-002542-f7l4ty2j 158 6 live live JJ cord-002542-f7l4ty2j 158 7 cells cell NNS cord-002542-f7l4ty2j 158 8 was be VBD cord-002542-f7l4ty2j 158 9 based base VBN cord-002542-f7l4ty2j 158 10 on on IN cord-002542-f7l4ty2j 158 11 scattering scatter VBG cord-002542-f7l4ty2j 158 12 features feature NNS cord-002542-f7l4ty2j 158 13 of of IN cord-002542-f7l4ty2j 158 14 the the DT cord-002542-f7l4ty2j 158 15 negative negative JJ cord-002542-f7l4ty2j 158 16 controls control NNS cord-002542-f7l4ty2j 158 17 ( ( -LRB- cord-002542-f7l4ty2j 158 18 wells well NNS cord-002542-f7l4ty2j 158 19 with with IN cord-002542-f7l4ty2j 158 20 no no DT cord-002542-f7l4ty2j 158 21 viral viral JJ cord-002542-f7l4ty2j 158 22 infection infection NN cord-002542-f7l4ty2j 158 23 ) ) -RRB- cord-002542-f7l4ty2j 159 1 ( ( -LRB- cord-002542-f7l4ty2j 159 2 S7 S7 NNP cord-002542-f7l4ty2j 159 3 Fig Fig NNP cord-002542-f7l4ty2j 159 4 ) ) -RRB- cord-002542-f7l4ty2j 159 5 . . . cord-002542-f7l4ty2j 160 1 All all DT cord-002542-f7l4ty2j 160 2 raw raw JJ cord-002542-f7l4ty2j 160 3 Illumina Illumina NNP cord-002542-f7l4ty2j 160 4 data datum NNS cord-002542-f7l4ty2j 160 5 and and CC cord-002542-f7l4ty2j 160 6 demultiplexed demultiplexed NNP cord-002542-f7l4ty2j 160 7 MinION MinION NNP cord-002542-f7l4ty2j 160 8 nanopore nanopore NNP cord-002542-f7l4ty2j 160 9 data datum NNS cord-002542-f7l4ty2j 160 10 passing pass VBG cord-002542-f7l4ty2j 160 11 quality quality NN cord-002542-f7l4ty2j 160 12 filters filter NNS cord-002542-f7l4ty2j 160 13 ( ( -LRB- cord-002542-f7l4ty2j 160 14 comprising comprise VBG cord-002542-f7l4ty2j 160 15 2D 2D NNP cord-002542-f7l4ty2j 160 16 , , , cord-002542-f7l4ty2j 160 17 template template NN cord-002542-f7l4ty2j 160 18 and and CC cord-002542-f7l4ty2j 160 19 complement complement JJ cord-002542-f7l4ty2j 160 20 strands strand NNS cord-002542-f7l4ty2j 160 21 ) ) -RRB- cord-002542-f7l4ty2j 160 22 associated associate VBN cord-002542-f7l4ty2j 160 23 with with IN cord-002542-f7l4ty2j 160 24 this this DT cord-002542-f7l4ty2j 160 25 manuscript manuscript NN cord-002542-f7l4ty2j 160 26 are be VBP cord-002542-f7l4ty2j 160 27 available available JJ cord-002542-f7l4ty2j 160 28 on on IN cord-002542-f7l4ty2j 160 29 the the DT cord-002542-f7l4ty2j 160 30 SRA SRA NNP cord-002542-f7l4ty2j 160 31 NCBI NCBI NNP cord-002542-f7l4ty2j 160 32 archive archive NN cord-002542-f7l4ty2j 160 33 with with IN cord-002542-f7l4ty2j 160 34 study study NN cord-002542-f7l4ty2j 160 35 number number NN cord-002542-f7l4ty2j 160 36 SRP094723 srp094723 NN cord-002542-f7l4ty2j 160 37 and and CC cord-002542-f7l4ty2j 161 1 BioProject BioProject NNP cord-002542-f7l4ty2j 161 2 number number NN cord-002542-f7l4ty2j 161 3 PRJNA352872 PRJNA352872 NNP cord-002542-f7l4ty2j 161 4 . . . cord-002542-f7l4ty2j 162 1 D. D. NNP cord-002542-f7l4ty2j 162 2 melanogaster melanogaster NNP cord-002542-f7l4ty2j 162 3 ( ( -LRB- cord-002542-f7l4ty2j 162 4 S2 S2 NNP cord-002542-f7l4ty2j 162 5 ) ) -RRB- cord-002542-f7l4ty2j 162 6 cells cell NNS cord-002542-f7l4ty2j 162 7 in in IN cord-002542-f7l4ty2j 162 8 culture culture NN cord-002542-f7l4ty2j 162 9 were be VBD cord-002542-f7l4ty2j 162 10 transfected transfecte VBN cord-002542-f7l4ty2j 162 11 with with IN cord-002542-f7l4ty2j 162 12 cDNA cdna NN cord-002542-f7l4ty2j 162 13 plasmids plasmid NNS cord-002542-f7l4ty2j 162 14 containing contain VBG cord-002542-f7l4ty2j 162 15 each each DT cord-002542-f7l4ty2j 162 16 of of IN cord-002542-f7l4ty2j 162 17 the the DT cord-002542-f7l4ty2j 162 18 Flock Flock NNP cord-002542-f7l4ty2j 162 19 House House NNP cord-002542-f7l4ty2j 162 20 virus virus NN cord-002542-f7l4ty2j 162 21 genomic genomic JJ cord-002542-f7l4ty2j 162 22 RNAs rna NNS cord-002542-f7l4ty2j 162 23 followed follow VBN cord-002542-f7l4ty2j 162 24 by by IN cord-002542-f7l4ty2j 162 25 a a DT cord-002542-f7l4ty2j 162 26 hepatitis hepatitis NN cord-002542-f7l4ty2j 162 27 D d NN cord-002542-f7l4ty2j 162 28 virus virus NN cord-002542-f7l4ty2j 162 29 ( ( -LRB- cord-002542-f7l4ty2j 162 30 HDV HDV NNP cord-002542-f7l4ty2j 162 31 ) ) -RRB- cord-002542-f7l4ty2j 162 32 ribozyme ribozyme NN cord-002542-f7l4ty2j 162 33 sequence sequence NN cord-002542-f7l4ty2j 162 34 . . . cord-002542-f7l4ty2j 163 1 After after IN cord-002542-f7l4ty2j 163 2 induction induction NN cord-002542-f7l4ty2j 163 3 , , , cord-002542-f7l4ty2j 163 4 the the DT cord-002542-f7l4ty2j 163 5 HDV HDV NNP cord-002542-f7l4ty2j 163 6 ribozyme ribozyme NN cord-002542-f7l4ty2j 163 7 regenerates regenerate VBZ cord-002542-f7l4ty2j 163 8 the the DT cord-002542-f7l4ty2j 163 9 authentic authentic JJ cord-002542-f7l4ty2j 163 10 3 3 CD cord-002542-f7l4ty2j 163 11 ' ' NN cord-002542-f7l4ty2j 163 12 end end NN cord-002542-f7l4ty2j 163 13 of of IN cord-002542-f7l4ty2j 163 14 the the DT cord-002542-f7l4ty2j 163 15 positive positive JJ cord-002542-f7l4ty2j 163 16 sense sense NN cord-002542-f7l4ty2j 163 17 viral viral JJ cord-002542-f7l4ty2j 163 18 RNA RNA NNP cord-002542-f7l4ty2j 163 19 , , , cord-002542-f7l4ty2j 163 20 which which WDT cord-002542-f7l4ty2j 163 21 is be VBZ cord-002542-f7l4ty2j 163 22 thus thus RB cord-002542-f7l4ty2j 163 23 successfully successfully RB cord-002542-f7l4ty2j 163 24 recognized recognize VBN cord-002542-f7l4ty2j 163 25 by by IN cord-002542-f7l4ty2j 163 26 the the DT cord-002542-f7l4ty2j 163 27 FHV FHV NNP cord-002542-f7l4ty2j 163 28 RdRp RdRp NNP cord-002542-f7l4ty2j 163 29 allowing allow VBG cord-002542-f7l4ty2j 163 30 the the DT cord-002542-f7l4ty2j 163 31 initiation initiation NN cord-002542-f7l4ty2j 163 32 of of IN cord-002542-f7l4ty2j 163 33 viral viral JJ cord-002542-f7l4ty2j 163 34 replication replication NN cord-002542-f7l4ty2j 163 35 [ [ -LRB- cord-002542-f7l4ty2j 163 36 54 54 CD cord-002542-f7l4ty2j 163 37 ] ] -RRB- cord-002542-f7l4ty2j 163 38 . . . cord-002542-f7l4ty2j 164 1 We -PRON- PRP cord-002542-f7l4ty2j 164 2 choose choose VBP cord-002542-f7l4ty2j 164 3 to to TO cord-002542-f7l4ty2j 164 4 initiate initiate VB cord-002542-f7l4ty2j 164 5 replication replication NN cord-002542-f7l4ty2j 164 6 with with IN cord-002542-f7l4ty2j 164 7 this this DT cord-002542-f7l4ty2j 164 8 method method NN cord-002542-f7l4ty2j 164 9 to to TO cord-002542-f7l4ty2j 164 10 ensure ensure VB cord-002542-f7l4ty2j 164 11 that that IN cord-002542-f7l4ty2j 164 12 the the DT cord-002542-f7l4ty2j 164 13 starting start VBG cord-002542-f7l4ty2j 164 14 viral viral JJ cord-002542-f7l4ty2j 164 15 population population NN cord-002542-f7l4ty2j 164 16 would would MD cord-002542-f7l4ty2j 164 17 be be VB cord-002542-f7l4ty2j 164 18 homogeneous homogeneous JJ cord-002542-f7l4ty2j 164 19 containing contain VBG cord-002542-f7l4ty2j 164 20 only only RB cord-002542-f7l4ty2j 164 21 the the DT cord-002542-f7l4ty2j 164 22 full full JJ cord-002542-f7l4ty2j 164 23 - - HYPH cord-002542-f7l4ty2j 164 24 length length NN cord-002542-f7l4ty2j 164 25 RNAs rna NNS cord-002542-f7l4ty2j 164 26 derived derive VBN cord-002542-f7l4ty2j 164 27 from from IN cord-002542-f7l4ty2j 164 28 the the DT cord-002542-f7l4ty2j 164 29 plasmid plasmid NN cord-002542-f7l4ty2j 164 30 cDNA cdna NN cord-002542-f7l4ty2j 164 31 . . . cord-002542-f7l4ty2j 165 1 After after IN cord-002542-f7l4ty2j 165 2 transfection transfection NN cord-002542-f7l4ty2j 165 3 , , , cord-002542-f7l4ty2j 165 4 the the DT cord-002542-f7l4ty2j 165 5 viral viral JJ cord-002542-f7l4ty2j 165 6 inoculum inoculum NN cord-002542-f7l4ty2j 165 7 was be VBD cord-002542-f7l4ty2j 165 8 allowed allow VBN cord-002542-f7l4ty2j 165 9 to to TO cord-002542-f7l4ty2j 165 10 amplify amplify VB cord-002542-f7l4ty2j 165 11 for for IN cord-002542-f7l4ty2j 165 12 3 3 CD cord-002542-f7l4ty2j 165 13 days day NNS cord-002542-f7l4ty2j 165 14 ( ( -LRB- cord-002542-f7l4ty2j 165 15 Passage passage NN cord-002542-f7l4ty2j 165 16 number number NN cord-002542-f7l4ty2j 165 17 = = SYM cord-002542-f7l4ty2j 165 18 P0 p0 NN cord-002542-f7l4ty2j 165 19 ) ) -RRB- cord-002542-f7l4ty2j 165 20 , , , cord-002542-f7l4ty2j 165 21 after after IN cord-002542-f7l4ty2j 165 22 which which WDT cord-002542-f7l4ty2j 165 23 most most JJS cord-002542-f7l4ty2j 165 24 cells cell NNS cord-002542-f7l4ty2j 165 25 exhibited exhibit VBD cord-002542-f7l4ty2j 165 26 cytopathic cytopathic JJ cord-002542-f7l4ty2j 165 27 effect effect NN cord-002542-f7l4ty2j 165 28 . . . cord-002542-f7l4ty2j 166 1 Subsequently subsequently RB cord-002542-f7l4ty2j 166 2 , , , cord-002542-f7l4ty2j 166 3 the the DT cord-002542-f7l4ty2j 166 4 supernatant supernatant NN cord-002542-f7l4ty2j 166 5 from from IN cord-002542-f7l4ty2j 166 6 infected infected JJ cord-002542-f7l4ty2j 166 7 cells cell NNS cord-002542-f7l4ty2j 166 8 was be VBD cord-002542-f7l4ty2j 166 9 collected collect VBN cord-002542-f7l4ty2j 166 10 and and CC cord-002542-f7l4ty2j 166 11 a a DT cord-002542-f7l4ty2j 166 12 1mL 1ml CD cord-002542-f7l4ty2j 166 13 fraction fraction NN cord-002542-f7l4ty2j 166 14 ( ( -LRB- cord-002542-f7l4ty2j 166 15 10 10 CD cord-002542-f7l4ty2j 166 16 % % NN cord-002542-f7l4ty2j 166 17 of of IN cord-002542-f7l4ty2j 166 18 the the DT cord-002542-f7l4ty2j 166 19 total total JJ cord-002542-f7l4ty2j 166 20 volume volume NN cord-002542-f7l4ty2j 166 21 ) ) -RRB- cord-002542-f7l4ty2j 166 22 was be VBD cord-002542-f7l4ty2j 166 23 used use VBN cord-002542-f7l4ty2j 166 24 to to TO cord-002542-f7l4ty2j 166 25 infect infect VB cord-002542-f7l4ty2j 166 26 10mL 10ml CD cord-002542-f7l4ty2j 166 27 of of IN cord-002542-f7l4ty2j 166 28 fresh fresh JJ cord-002542-f7l4ty2j 166 29 S2 s2 NN cord-002542-f7l4ty2j 166 30 cells cell NNS cord-002542-f7l4ty2j 166 31 in in IN cord-002542-f7l4ty2j 166 32 triplicate triplicate NN cord-002542-f7l4ty2j 166 33 ( ( -LRB- cord-002542-f7l4ty2j 166 34 Replicates replicate VBZ cord-002542-f7l4ty2j 166 35 R1 R1 NNP cord-002542-f7l4ty2j 166 36 , , , cord-002542-f7l4ty2j 166 37 R2 R2 NNP cord-002542-f7l4ty2j 166 38 , , , cord-002542-f7l4ty2j 166 39 and and CC cord-002542-f7l4ty2j 166 40 R3 R3 NNP cord-002542-f7l4ty2j 166 41 ) ) -RRB- cord-002542-f7l4ty2j 166 42 . . . cord-002542-f7l4ty2j 167 1 Again again RB cord-002542-f7l4ty2j 167 2 , , , cord-002542-f7l4ty2j 167 3 after after IN cord-002542-f7l4ty2j 167 4 three three CD cord-002542-f7l4ty2j 167 5 days day NNS cord-002542-f7l4ty2j 167 6 , , , cord-002542-f7l4ty2j 167 7 1mL 1ml CD cord-002542-f7l4ty2j 167 8 of of IN cord-002542-f7l4ty2j 167 9 the the DT cord-002542-f7l4ty2j 167 10 supernatant supernatant NN cord-002542-f7l4ty2j 167 11 was be VBD cord-002542-f7l4ty2j 167 12 harvested harvest VBN cord-002542-f7l4ty2j 167 13 and and CC cord-002542-f7l4ty2j 167 14 used use VBN cord-002542-f7l4ty2j 167 15 to to TO cord-002542-f7l4ty2j 167 16 infect infect VB cord-002542-f7l4ty2j 167 17 fresh fresh JJ cord-002542-f7l4ty2j 167 18 S2 s2 NN cord-002542-f7l4ty2j 167 19 cells cell NNS cord-002542-f7l4ty2j 167 20 in in IN cord-002542-f7l4ty2j 167 21 series series NN cord-002542-f7l4ty2j 167 22 for for IN cord-002542-f7l4ty2j 167 23 a a DT cord-002542-f7l4ty2j 167 24 total total NN cord-002542-f7l4ty2j 167 25 of of IN cord-002542-f7l4ty2j 167 26 nine nine CD cord-002542-f7l4ty2j 167 27 3-day 3-day JJ cord-002542-f7l4ty2j 167 28 passages passage NNS cord-002542-f7l4ty2j 167 29 ( ( -LRB- cord-002542-f7l4ty2j 167 30 Passage passage NN cord-002542-f7l4ty2j 167 31 numbers number NNS cord-002542-f7l4ty2j 167 32 = = SYM cord-002542-f7l4ty2j 167 33 P1 P1 NNP cord-002542-f7l4ty2j 167 34 -P9 -p9 NN cord-002542-f7l4ty2j 167 35 ) ) -RRB- cord-002542-f7l4ty2j 167 36 . . . cord-002542-f7l4ty2j 168 1 Therefore therefore RB cord-002542-f7l4ty2j 168 2 , , , cord-002542-f7l4ty2j 168 3 one one CD cord-002542-f7l4ty2j 168 4 single single JJ cord-002542-f7l4ty2j 168 5 inoculum inoculum NN cord-002542-f7l4ty2j 168 6 was be VBD cord-002542-f7l4ty2j 168 7 used use VBN cord-002542-f7l4ty2j 168 8 to to TO cord-002542-f7l4ty2j 168 9 generate generate VB cord-002542-f7l4ty2j 168 10 three three CD cord-002542-f7l4ty2j 168 11 distinct distinct JJ cord-002542-f7l4ty2j 168 12 lineages lineage NNS cord-002542-f7l4ty2j 168 13 as as IN cord-002542-f7l4ty2j 168 14 shown show VBN cord-002542-f7l4ty2j 168 15 in in IN cord-002542-f7l4ty2j 168 16 Fig Fig NNP cord-002542-f7l4ty2j 168 17 1 1 CD cord-002542-f7l4ty2j 168 18 . . . cord-002542-f7l4ty2j 169 1 For for IN cord-002542-f7l4ty2j 169 2 each each DT cord-002542-f7l4ty2j 169 3 passage passage NN cord-002542-f7l4ty2j 169 4 and and CC cord-002542-f7l4ty2j 169 5 replicate replicate VB cord-002542-f7l4ty2j 169 6 , , , cord-002542-f7l4ty2j 169 7 including include VBG cord-002542-f7l4ty2j 169 8 the the DT cord-002542-f7l4ty2j 169 9 original original JJ cord-002542-f7l4ty2j 169 10 inoculum inoculum NN cord-002542-f7l4ty2j 169 11 , , , cord-002542-f7l4ty2j 169 12 viral viral JJ cord-002542-f7l4ty2j 169 13 particles particle NNS cord-002542-f7l4ty2j 169 14 were be VBD cord-002542-f7l4ty2j 169 15 purified purify VBN cord-002542-f7l4ty2j 169 16 over over IN cord-002542-f7l4ty2j 169 17 a a DT cord-002542-f7l4ty2j 169 18 sucrose sucrose NN cord-002542-f7l4ty2j 169 19 cushion cushion NN cord-002542-f7l4ty2j 169 20 and and CC cord-002542-f7l4ty2j 169 21 non non JJ cord-002542-f7l4ty2j 169 22 - - JJ cord-002542-f7l4ty2j 169 23 encapsidated encapsidated JJ cord-002542-f7l4ty2j 169 24 genetic genetic JJ cord-002542-f7l4ty2j 169 25 material material NN cord-002542-f7l4ty2j 169 26 was be VBD cord-002542-f7l4ty2j 169 27 degraded degrade VBN cord-002542-f7l4ty2j 169 28 to to TO cord-002542-f7l4ty2j 169 29 ensure ensure VB cord-002542-f7l4ty2j 169 30 that that IN cord-002542-f7l4ty2j 169 31 the the DT cord-002542-f7l4ty2j 169 32 genetic genetic JJ cord-002542-f7l4ty2j 169 33 material material NN cord-002542-f7l4ty2j 169 34 subsequently subsequently RB cord-002542-f7l4ty2j 169 35 analyzed analyze VBN cord-002542-f7l4ty2j 169 36 was be VBD cord-002542-f7l4ty2j 169 37 packaged package VBN cord-002542-f7l4ty2j 169 38 within within IN cord-002542-f7l4ty2j 169 39 the the DT cord-002542-f7l4ty2j 169 40 viral viral JJ cord-002542-f7l4ty2j 169 41 capsid capsid NN cord-002542-f7l4ty2j 169 42 . . . cord-002542-f7l4ty2j 170 1 RNA RNA NNP cord-002542-f7l4ty2j 170 2 was be VBD cord-002542-f7l4ty2j 170 3 extracted extract VBN cord-002542-f7l4ty2j 170 4 from from IN cord-002542-f7l4ty2j 170 5 the the DT cord-002542-f7l4ty2j 170 6 purified purify VBN cord-002542-f7l4ty2j 170 7 viral viral JJ cord-002542-f7l4ty2j 170 8 particles particle NNS cord-002542-f7l4ty2j 170 9 using use VBG cord-002542-f7l4ty2j 170 10 standard standard JJ cord-002542-f7l4ty2j 170 11 silica silica NN cord-002542-f7l4ty2j 170 12 - - HYPH cord-002542-f7l4ty2j 170 13 based base VBN cord-002542-f7l4ty2j 170 14 spin spin NN cord-002542-f7l4ty2j 170 15 columns column NNS cord-002542-f7l4ty2j 170 16 . . . cord-002542-f7l4ty2j 171 1 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 171 2 libraries library NNS cord-002542-f7l4ty2j 171 3 [ [ -LRB- cord-002542-f7l4ty2j 171 4 35 35 CD cord-002542-f7l4ty2j 171 5 ] ] -RRB- cord-002542-f7l4ty2j 171 6 were be VBD cord-002542-f7l4ty2j 171 7 synthesized synthesize VBN cord-002542-f7l4ty2j 171 8 from from IN cord-002542-f7l4ty2j 171 9 the the DT cord-002542-f7l4ty2j 171 10 purified purify VBN cord-002542-f7l4ty2j 171 11 viral viral JJ cord-002542-f7l4ty2j 171 12 genomic genomic NN cord-002542-f7l4ty2j 171 13 RNA RNA NNP cord-002542-f7l4ty2j 171 14 and and CC cord-002542-f7l4ty2j 171 15 sequenced sequence VBN cord-002542-f7l4ty2j 171 16 on on IN cord-002542-f7l4ty2j 171 17 an an DT cord-002542-f7l4ty2j 171 18 Illumina Illumina NNP cord-002542-f7l4ty2j 171 19 HiSeq HiSeq NNP cord-002542-f7l4ty2j 171 20 1500 1500 CD cord-002542-f7l4ty2j 171 21 for for IN cord-002542-f7l4ty2j 171 22 1x150 1x150 CD cord-002542-f7l4ty2j 171 23 single single JJ cord-002542-f7l4ty2j 171 24 - - HYPH cord-002542-f7l4ty2j 171 25 end end NN cord-002542-f7l4ty2j 171 26 reads read NNS cord-002542-f7l4ty2j 171 27 . . . cord-002542-f7l4ty2j 172 1 The the DT cord-002542-f7l4ty2j 172 2 inoculum inoculum NN cord-002542-f7l4ty2j 172 3 sample sample NN cord-002542-f7l4ty2j 172 4 was be VBD cord-002542-f7l4ty2j 172 5 sequenced sequence VBN cord-002542-f7l4ty2j 172 6 on on IN cord-002542-f7l4ty2j 172 7 a a DT cord-002542-f7l4ty2j 172 8 separate separate JJ cord-002542-f7l4ty2j 172 9 flowcell flowcell NN cord-002542-f7l4ty2j 172 10 to to IN cord-002542-f7l4ty2j 172 11 all all DT cord-002542-f7l4ty2j 172 12 other other JJ cord-002542-f7l4ty2j 172 13 samples sample NNS cord-002542-f7l4ty2j 172 14 to to TO cord-002542-f7l4ty2j 172 15 prevent prevent VB cord-002542-f7l4ty2j 172 16 any any DT cord-002542-f7l4ty2j 172 17 cross cross NN cord-002542-f7l4ty2j 172 18 - - NN cord-002542-f7l4ty2j 172 19 contamination contamination NN cord-002542-f7l4ty2j 172 20 from from IN cord-002542-f7l4ty2j 172 21 incorrect incorrect JJ cord-002542-f7l4ty2j 172 22 demultiplexing demultiplexing NN cord-002542-f7l4ty2j 172 23 . . . cord-002542-f7l4ty2j 173 1 We -PRON- PRP cord-002542-f7l4ty2j 173 2 obtained obtain VBD cord-002542-f7l4ty2j 173 3 1.2 1.2 CD cord-002542-f7l4ty2j 173 4 - - SYM cord-002542-f7l4ty2j 173 5 30.6 30.6 CD cord-002542-f7l4ty2j 173 6 million million CD cord-002542-f7l4ty2j 173 7 reads read VBZ cord-002542-f7l4ty2j 173 8 after after IN cord-002542-f7l4ty2j 173 9 trimming trim VBG cord-002542-f7l4ty2j 173 10 and and CC cord-002542-f7l4ty2j 173 11 quality quality NN cord-002542-f7l4ty2j 173 12 filtering filter VBG cord-002542-f7l4ty2j 173 13 for for IN cord-002542-f7l4ty2j 173 14 each each DT cord-002542-f7l4ty2j 173 15 passaged passage VBN cord-002542-f7l4ty2j 173 16 sample sample NN cord-002542-f7l4ty2j 173 17 , , , cord-002542-f7l4ty2j 173 18 and and CC cord-002542-f7l4ty2j 173 19 41.6 41.6 CD cord-002542-f7l4ty2j 173 20 million million CD cord-002542-f7l4ty2j 173 21 reads read VBZ cord-002542-f7l4ty2j 173 22 for for IN cord-002542-f7l4ty2j 173 23 the the DT cord-002542-f7l4ty2j 173 24 original original JJ cord-002542-f7l4ty2j 173 25 inoculum inoculum NN cord-002542-f7l4ty2j 173 26 ( ( -LRB- cord-002542-f7l4ty2j 173 27 Table table NN cord-002542-f7l4ty2j 173 28 1 1 CD cord-002542-f7l4ty2j 173 29 and and CC cord-002542-f7l4ty2j 173 30 S1 S1 NNP cord-002542-f7l4ty2j 173 31 Table Table NNP cord-002542-f7l4ty2j 173 32 ) ) -RRB- cord-002542-f7l4ty2j 173 33 . . . cord-002542-f7l4ty2j 174 1 1 1 CD cord-002542-f7l4ty2j 174 2 million million CD cord-002542-f7l4ty2j 174 3 reads read NNS cord-002542-f7l4ty2j 174 4 corresponds correspond VBZ cord-002542-f7l4ty2j 174 5 to to IN cord-002542-f7l4ty2j 174 6 an an DT cord-002542-f7l4ty2j 174 7 average average JJ cord-002542-f7l4ty2j 174 8 coverage coverage NN cord-002542-f7l4ty2j 174 9 of of IN cord-002542-f7l4ty2j 174 10 greater great JJR cord-002542-f7l4ty2j 174 11 than than IN cord-002542-f7l4ty2j 174 12 33'000X 33'000X NNP cord-002542-f7l4ty2j 174 13 across across IN cord-002542-f7l4ty2j 174 14 the the DT cord-002542-f7l4ty2j 174 15 FHV FHV NNP cord-002542-f7l4ty2j 174 16 genome genome NN cord-002542-f7l4ty2j 174 17 . . . cord-002542-f7l4ty2j 175 1 Reads read NNS cord-002542-f7l4ty2j 175 2 were be VBD cord-002542-f7l4ty2j 175 3 aligned align VBN cord-002542-f7l4ty2j 175 4 to to IN cord-002542-f7l4ty2j 175 5 the the DT cord-002542-f7l4ty2j 175 6 FHV FHV NNP cord-002542-f7l4ty2j 175 7 genome genome NN cord-002542-f7l4ty2j 175 8 and and CC cord-002542-f7l4ty2j 175 9 the the DT cord-002542-f7l4ty2j 175 10 host host NN cord-002542-f7l4ty2j 175 11 genome genome NN cord-002542-f7l4ty2j 175 12 ( ( -LRB- cord-002542-f7l4ty2j 175 13 D. D. NNP cord-002542-f7l4ty2j 175 14 melanogaster melanogaster NN cord-002542-f7l4ty2j 175 15 , , , cord-002542-f7l4ty2j 175 16 fb5_22 fb5_22 NN cord-002542-f7l4ty2j 175 17 ) ) -RRB- cord-002542-f7l4ty2j 175 18 using use VBG cord-002542-f7l4ty2j 175 19 Bowtie Bowtie NNP cord-002542-f7l4ty2j 175 20 end end NN cord-002542-f7l4ty2j 175 21 - - HYPH cord-002542-f7l4ty2j 175 22 to to IN cord-002542-f7l4ty2j 175 23 - - HYPH cord-002542-f7l4ty2j 175 24 end end NN cord-002542-f7l4ty2j 175 25 mapping mapping NN cord-002542-f7l4ty2j 175 26 [ [ -LRB- cord-002542-f7l4ty2j 175 27 47 47 CD cord-002542-f7l4ty2j 175 28 ] ] -RRB- cord-002542-f7l4ty2j 175 29 . . . cord-002542-f7l4ty2j 176 1 As as IN cord-002542-f7l4ty2j 176 2 expected expect VBN cord-002542-f7l4ty2j 176 3 , , , cord-002542-f7l4ty2j 176 4 the the DT cord-002542-f7l4ty2j 176 5 majority majority NN cord-002542-f7l4ty2j 176 6 of of IN cord-002542-f7l4ty2j 176 7 the the DT cord-002542-f7l4ty2j 176 8 reads read NNS cord-002542-f7l4ty2j 176 9 aligned align VBN cord-002542-f7l4ty2j 176 10 to to IN cord-002542-f7l4ty2j 176 11 FHV FHV NNP cord-002542-f7l4ty2j 176 12 RNA1 RNA1 NNP cord-002542-f7l4ty2j 176 13 ( ( -LRB- cord-002542-f7l4ty2j 176 14 3107 3107 CD cord-002542-f7l4ty2j 176 15 nts nts NNPS cord-002542-f7l4ty2j 176 16 ) ) -RRB- cord-002542-f7l4ty2j 176 17 and and CC cord-002542-f7l4ty2j 176 18 FHV FHV NNP cord-002542-f7l4ty2j 176 19 RNA2 RNA2 NNP cord-002542-f7l4ty2j 177 1 ( ( -LRB- cord-002542-f7l4ty2j 177 2 1400 1400 CD cord-002542-f7l4ty2j 177 3 nts nts NNPS cord-002542-f7l4ty2j 177 4 ) ) -RRB- cord-002542-f7l4ty2j 177 5 in in IN cord-002542-f7l4ty2j 177 6 a a DT cord-002542-f7l4ty2j 177 7 ratio ratio NN cord-002542-f7l4ty2j 177 8 reflecting reflect VBG cord-002542-f7l4ty2j 177 9 the the DT cord-002542-f7l4ty2j 177 10 longer long JJR cord-002542-f7l4ty2j 177 11 length length NN cord-002542-f7l4ty2j 177 12 of of IN cord-002542-f7l4ty2j 177 13 RNA1 RNA1 NNP cord-002542-f7l4ty2j 177 14 . . . cord-002542-f7l4ty2j 178 1 As as IN cord-002542-f7l4ty2j 178 2 we -PRON- PRP cord-002542-f7l4ty2j 178 3 have have VBP cord-002542-f7l4ty2j 178 4 observed observe VBN cord-002542-f7l4ty2j 178 5 previously previously RB cord-002542-f7l4ty2j 178 6 [ [ -LRB- cord-002542-f7l4ty2j 178 7 34 34 CD cord-002542-f7l4ty2j 178 8 , , , cord-002542-f7l4ty2j 178 9 55 55 CD cord-002542-f7l4ty2j 178 10 ] ] -RRB- cord-002542-f7l4ty2j 178 11 , , , cord-002542-f7l4ty2j 178 12 0.3 0.3 CD cord-002542-f7l4ty2j 178 13 - - SYM cord-002542-f7l4ty2j 178 14 8.4 8.4 CD cord-002542-f7l4ty2j 178 15 % % NN cord-002542-f7l4ty2j 178 16 of of IN cord-002542-f7l4ty2j 178 17 reads read NNS cord-002542-f7l4ty2j 178 18 correspond correspond VBP cord-002542-f7l4ty2j 178 19 to to TO cord-002542-f7l4ty2j 178 20 host host VB cord-002542-f7l4ty2j 178 21 RNAs rna NNS cord-002542-f7l4ty2j 178 22 that that WDT cord-002542-f7l4ty2j 178 23 are be VBP cord-002542-f7l4ty2j 178 24 encapsidated encapsidate VBN cord-002542-f7l4ty2j 178 25 within within IN cord-002542-f7l4ty2j 178 26 the the DT cord-002542-f7l4ty2j 178 27 viral viral JJ cord-002542-f7l4ty2j 178 28 particles particle NNS cord-002542-f7l4ty2j 178 29 including include VBG cord-002542-f7l4ty2j 178 30 mRNAs mrnas ADD cord-002542-f7l4ty2j 178 31 , , , cord-002542-f7l4ty2j 178 32 ribosomal ribosomal JJ cord-002542-f7l4ty2j 178 33 RNAs rna NNS cord-002542-f7l4ty2j 178 34 and and CC cord-002542-f7l4ty2j 178 35 retrotransposons retrotransposon NNS cord-002542-f7l4ty2j 178 36 . . . cord-002542-f7l4ty2j 179 1 Interestingly interestingly RB cord-002542-f7l4ty2j 179 2 , , , cord-002542-f7l4ty2j 179 3 the the DT cord-002542-f7l4ty2j 179 4 amount amount NN cord-002542-f7l4ty2j 179 5 of of IN cord-002542-f7l4ty2j 179 6 encapsidated encapsidated JJ cord-002542-f7l4ty2j 179 7 host host NN cord-002542-f7l4ty2j 179 8 RNA RNA NNP cord-002542-f7l4ty2j 179 9 increases increase VBZ cord-002542-f7l4ty2j 179 10 modestly modestly RB cord-002542-f7l4ty2j 179 11 through through IN cord-002542-f7l4ty2j 179 12 later later JJ cord-002542-f7l4ty2j 179 13 passages passage NNS cord-002542-f7l4ty2j 179 14 ( ( -LRB- cord-002542-f7l4ty2j 179 15 S1 S1 NNP cord-002542-f7l4ty2j 179 16 Fig Fig NNP cord-002542-f7l4ty2j 179 17 ) ) -RRB- cord-002542-f7l4ty2j 179 18 . . . cord-002542-f7l4ty2j 180 1 Subsequently subsequently RB cord-002542-f7l4ty2j 180 2 , , , cord-002542-f7l4ty2j 180 3 we -PRON- PRP cord-002542-f7l4ty2j 180 4 further further RB cord-002542-f7l4ty2j 180 5 characterized characterize VBD cord-002542-f7l4ty2j 180 6 the the DT cord-002542-f7l4ty2j 180 7 unmapped unmapped JJ cord-002542-f7l4ty2j 180 8 reads read NNS cord-002542-f7l4ty2j 180 9 with with IN cord-002542-f7l4ty2j 180 10 the the DT cord-002542-f7l4ty2j 180 11 Python Python NNP cord-002542-f7l4ty2j 180 12 script script NN cord-002542-f7l4ty2j 180 13 ViReMa virema NN cord-002542-f7l4ty2j 180 14 ( ( -LRB- cord-002542-f7l4ty2j 180 15 " " `` cord-002542-f7l4ty2j 180 16 Virus Virus NNP cord-002542-f7l4ty2j 180 17 Recombination Recombination NNP cord-002542-f7l4ty2j 180 18 Mapper Mapper NNP cord-002542-f7l4ty2j 180 19 " " '' cord-002542-f7l4ty2j 180 20 ) ) -RRB- cord-002542-f7l4ty2j 180 21 [ [ -LRB- cord-002542-f7l4ty2j 180 22 32 32 CD cord-002542-f7l4ty2j 180 23 ] ] -RRB- cord-002542-f7l4ty2j 180 24 . . . cord-002542-f7l4ty2j 181 1 ViReMa ViReMa NNP cord-002542-f7l4ty2j 181 2 is be VBZ cord-002542-f7l4ty2j 181 3 a a DT cord-002542-f7l4ty2j 181 4 computational computational JJ cord-002542-f7l4ty2j 181 5 pipeline pipeline NN cord-002542-f7l4ty2j 181 6 optimized optimize VBN cord-002542-f7l4ty2j 181 7 for for IN cord-002542-f7l4ty2j 181 8 mapping mapping NN cord-002542-f7l4ty2j 181 9 virus virus NN cord-002542-f7l4ty2j 181 10 recombination recombination NN cord-002542-f7l4ty2j 181 11 junctions junction NNS cord-002542-f7l4ty2j 181 12 in in IN cord-002542-f7l4ty2j 181 13 NGS NGS NNP cord-002542-f7l4ty2j 181 14 data datum NNS cord-002542-f7l4ty2j 181 15 with with IN cord-002542-f7l4ty2j 181 16 nucleotide nucleotide JJ cord-002542-f7l4ty2j 181 17 resolution resolution NN cord-002542-f7l4ty2j 181 18 by by IN cord-002542-f7l4ty2j 181 19 dynamically dynamically RB cord-002542-f7l4ty2j 181 20 generating generate VBG cord-002542-f7l4ty2j 181 21 moving move VBG cord-002542-f7l4ty2j 181 22 read read NN cord-002542-f7l4ty2j 181 23 segments segment NNS cord-002542-f7l4ty2j 181 24 . . . cord-002542-f7l4ty2j 182 1 ViReMa ViReMa NNP cord-002542-f7l4ty2j 182 2 is be VBZ cord-002542-f7l4ty2j 182 3 sensitive sensitive JJ cord-002542-f7l4ty2j 182 4 to to IN cord-002542-f7l4ty2j 182 5 many many JJ cord-002542-f7l4ty2j 182 6 types type NNS cord-002542-f7l4ty2j 182 7 of of IN cord-002542-f7l4ty2j 182 8 RNA RNA NNP cord-002542-f7l4ty2j 182 9 recombination recombination NN cord-002542-f7l4ty2j 182 10 events event NNS cord-002542-f7l4ty2j 182 11 . . . cord-002542-f7l4ty2j 183 1 This this DT cord-002542-f7l4ty2j 183 2 includes include VBZ cord-002542-f7l4ty2j 183 3 micro micro NNS cord-002542-f7l4ty2j 183 4 - - HYPH cord-002542-f7l4ty2j 183 5 insertions insertion NNS cord-002542-f7l4ty2j 183 6 and and CC cord-002542-f7l4ty2j 183 7 deletions deletion NNS cord-002542-f7l4ty2j 183 8 ( ( -LRB- cord-002542-f7l4ty2j 183 9 InDels indel NNS cord-002542-f7l4ty2j 183 10 comprising comprise VBG cord-002542-f7l4ty2j 183 11 5 5 CD cord-002542-f7l4ty2j 183 12 or or CC cord-002542-f7l4ty2j 183 13 fewer few JJR cord-002542-f7l4ty2j 183 14 nucleotides nucleotide NNS cord-002542-f7l4ty2j 183 15 ) ) -RRB- cord-002542-f7l4ty2j 183 16 , , , cord-002542-f7l4ty2j 183 17 duplications duplication NNS cord-002542-f7l4ty2j 183 18 , , , cord-002542-f7l4ty2j 183 19 deletions deletion NNS cord-002542-f7l4ty2j 183 20 , , , cord-002542-f7l4ty2j 183 21 inter inter JJ cord-002542-f7l4ty2j 183 22 - - JJ cord-002542-f7l4ty2j 183 23 RNA rna JJ cord-002542-f7l4ty2j 183 24 recombination recombination NN cord-002542-f7l4ty2j 183 25 ( ( -LRB- cord-002542-f7l4ty2j 183 26 denoting denote VBG cord-002542-f7l4ty2j 183 27 recombination recombination NN cord-002542-f7l4ty2j 183 28 between between IN cord-002542-f7l4ty2j 183 29 FHV FHV NNP cord-002542-f7l4ty2j 183 30 RNA1 RNA1 NNP cord-002542-f7l4ty2j 183 31 and and CC cord-002542-f7l4ty2j 183 32 RNA2 RNA2 NNP cord-002542-f7l4ty2j 183 33 ) ) -RRB- cord-002542-f7l4ty2j 183 34 and and CC cord-002542-f7l4ty2j 183 35 virus virus NN cord-002542-f7l4ty2j 183 36 - - HYPH cord-002542-f7l4ty2j 183 37 to to IN cord-002542-f7l4ty2j 183 38 - - HYPH cord-002542-f7l4ty2j 183 39 host host NN cord-002542-f7l4ty2j 183 40 recombination recombination NN cord-002542-f7l4ty2j 183 41 events event NNS cord-002542-f7l4ty2j 183 42 , , , cord-002542-f7l4ty2j 183 43 and and CC cord-002542-f7l4ty2j 183 44 reports report VBZ cord-002542-f7l4ty2j 183 45 both both CC cord-002542-f7l4ty2j 183 46 the the DT cord-002542-f7l4ty2j 183 47 identity identity NN cord-002542-f7l4ty2j 183 48 and and CC cord-002542-f7l4ty2j 183 49 frequency frequency NN cord-002542-f7l4ty2j 183 50 of of IN cord-002542-f7l4ty2j 183 51 recombination recombination NN cord-002542-f7l4ty2j 183 52 events event NNS cord-002542-f7l4ty2j 183 53 . . . cord-002542-f7l4ty2j 184 1 Recombination recombination NN cord-002542-f7l4ty2j 184 2 events event NNS cord-002542-f7l4ty2j 184 3 that that WDT cord-002542-f7l4ty2j 184 4 can can MD cord-002542-f7l4ty2j 184 5 not not RB cord-002542-f7l4ty2j 184 6 be be VB cord-002542-f7l4ty2j 184 7 unambiguously unambiguously RB cord-002542-f7l4ty2j 184 8 identified identify VBN cord-002542-f7l4ty2j 184 9 due due IN cord-002542-f7l4ty2j 184 10 to to IN cord-002542-f7l4ty2j 184 11 unmapped unmapped JJ cord-002542-f7l4ty2j 184 12 read read NN cord-002542-f7l4ty2j 184 13 segments segment NNS cord-002542-f7l4ty2j 184 14 , , , cord-002542-f7l4ty2j 185 1 mismatches mismatch NNS cord-002542-f7l4ty2j 185 2 occurring occur VBG cord-002542-f7l4ty2j 185 3 near near RB cord-002542-f7l4ty2j 185 4 to to IN cord-002542-f7l4ty2j 185 5 putative putative JJ cord-002542-f7l4ty2j 185 6 recombination recombination NN cord-002542-f7l4ty2j 185 7 events event NNS cord-002542-f7l4ty2j 185 8 , , , cord-002542-f7l4ty2j 185 9 or or CC cord-002542-f7l4ty2j 185 10 reads read VBZ cord-002542-f7l4ty2j 185 11 containing contain VBG cord-002542-f7l4ty2j 185 12 fragments fragment NNS cord-002542-f7l4ty2j 185 13 of of IN cord-002542-f7l4ty2j 185 14 sequencing sequencing NN cord-002542-f7l4ty2j 185 15 adaptors adaptor NNS cord-002542-f7l4ty2j 185 16 are be VBP cord-002542-f7l4ty2j 185 17 flagged flag VBN cord-002542-f7l4ty2j 185 18 as as IN cord-002542-f7l4ty2j 185 19 ' ' `` cord-002542-f7l4ty2j 185 20 other other JJ cord-002542-f7l4ty2j 185 21 ' ' '' cord-002542-f7l4ty2j 185 22 ( ( -LRB- cord-002542-f7l4ty2j 185 23 Table table NN cord-002542-f7l4ty2j 185 24 1 1 CD cord-002542-f7l4ty2j 185 25 ) ) -RRB- cord-002542-f7l4ty2j 185 26 [ [ -LRB- cord-002542-f7l4ty2j 185 27 32 32 CD cord-002542-f7l4ty2j 185 28 ] ] -RRB- cord-002542-f7l4ty2j 185 29 . . . cord-002542-f7l4ty2j 186 1 In in IN cord-002542-f7l4ty2j 186 2 each each DT cord-002542-f7l4ty2j 186 3 genomic genomic JJ cord-002542-f7l4ty2j 186 4 RNA RNA NNP cord-002542-f7l4ty2j 186 5 we -PRON- PRP cord-002542-f7l4ty2j 186 6 found find VBD cord-002542-f7l4ty2j 186 7 hundreds hundred NNS cord-002542-f7l4ty2j 186 8 of of IN cord-002542-f7l4ty2j 186 9 unique unique JJ cord-002542-f7l4ty2j 186 10 recombination recombination NN cord-002542-f7l4ty2j 186 11 events event NNS cord-002542-f7l4ty2j 186 12 , , , cord-002542-f7l4ty2j 186 13 reflecting reflect VBG cord-002542-f7l4ty2j 186 14 a a DT cord-002542-f7l4ty2j 186 15 diverse diverse JJ cord-002542-f7l4ty2j 186 16 and and CC cord-002542-f7l4ty2j 186 17 complex complex JJ cord-002542-f7l4ty2j 186 18 mutational mutational JJ cord-002542-f7l4ty2j 186 19 landscape landscape NN cord-002542-f7l4ty2j 186 20 ( ( -LRB- cord-002542-f7l4ty2j 186 21 S1 S1 NNP cord-002542-f7l4ty2j 186 22 Datafile Datafile NNP cord-002542-f7l4ty2j 186 23 ) ) -RRB- cord-002542-f7l4ty2j 186 24 . . . cord-002542-f7l4ty2j 187 1 Broadly broadly RB cord-002542-f7l4ty2j 187 2 , , , cord-002542-f7l4ty2j 187 3 we -PRON- PRP cord-002542-f7l4ty2j 187 4 see see VBP cord-002542-f7l4ty2j 187 5 an an DT cord-002542-f7l4ty2j 187 6 increase increase NN cord-002542-f7l4ty2j 187 7 in in IN cord-002542-f7l4ty2j 187 8 the the DT cord-002542-f7l4ty2j 187 9 total total JJ cord-002542-f7l4ty2j 187 10 number number NN cord-002542-f7l4ty2j 187 11 of of IN cord-002542-f7l4ty2j 187 12 recombination recombination NN cord-002542-f7l4ty2j 187 13 events event NNS cord-002542-f7l4ty2j 187 14 during during IN cord-002542-f7l4ty2j 187 15 serial serial JJ cord-002542-f7l4ty2j 187 16 passaging passaging NN cord-002542-f7l4ty2j 187 17 of of IN cord-002542-f7l4ty2j 187 18 FHV FHV NNP cord-002542-f7l4ty2j 187 19 and and CC cord-002542-f7l4ty2j 187 20 a a DT cord-002542-f7l4ty2j 187 21 corresponding corresponding JJ cord-002542-f7l4ty2j 187 22 increase increase NN cord-002542-f7l4ty2j 187 23 in in IN cord-002542-f7l4ty2j 187 24 the the DT cord-002542-f7l4ty2j 187 25 Shannon Shannon NNP cord-002542-f7l4ty2j 187 26 diversity diversity NN cord-002542-f7l4ty2j 187 27 index index NN cord-002542-f7l4ty2j 187 28 ( ( -LRB- cord-002542-f7l4ty2j 187 29 Fig Fig NNP cord-002542-f7l4ty2j 187 30 2A 2a CD cord-002542-f7l4ty2j 187 31 and and CC cord-002542-f7l4ty2j 187 32 2B 2b CD cord-002542-f7l4ty2j 187 33 ) ) -RRB- cord-002542-f7l4ty2j 187 34 . . . cord-002542-f7l4ty2j 188 1 Following follow VBG cord-002542-f7l4ty2j 188 2 these these DT cord-002542-f7l4ty2j 188 3 mapping mapping NN cord-002542-f7l4ty2j 188 4 procedures procedure NNS cord-002542-f7l4ty2j 188 5 , , , cord-002542-f7l4ty2j 188 6 few few JJ cord-002542-f7l4ty2j 188 7 reads read NNS cord-002542-f7l4ty2j 188 8 ( ( -LRB- cord-002542-f7l4ty2j 188 9 0 0 CD cord-002542-f7l4ty2j 188 10 - - SYM cord-002542-f7l4ty2j 188 11 1.2 1.2 CD cord-002542-f7l4ty2j 188 12 % % NN cord-002542-f7l4ty2j 188 13 , , , cord-002542-f7l4ty2j 188 14 Table table NN cord-002542-f7l4ty2j 188 15 1 1 CD cord-002542-f7l4ty2j 188 16 and and CC cord-002542-f7l4ty2j 188 17 S1 S1 NNP cord-002542-f7l4ty2j 188 18 Table Table NNP cord-002542-f7l4ty2j 188 19 ) ) -RRB- cord-002542-f7l4ty2j 188 20 remained remain VBD cord-002542-f7l4ty2j 188 21 uncharacterized uncharacterized JJ cord-002542-f7l4ty2j 188 22 . . . cord-002542-f7l4ty2j 189 1 As as IN cord-002542-f7l4ty2j 189 2 in in IN cord-002542-f7l4ty2j 189 3 previous previous JJ cord-002542-f7l4ty2j 189 4 studies study NNS cord-002542-f7l4ty2j 189 5 , , , cord-002542-f7l4ty2j 189 6 these these DT cord-002542-f7l4ty2j 189 7 were be VBD cord-002542-f7l4ty2j 189 8 found find VBN cord-002542-f7l4ty2j 189 9 to to TO cord-002542-f7l4ty2j 189 10 be be VB cord-002542-f7l4ty2j 189 11 derived derive VBN cord-002542-f7l4ty2j 189 12 from from IN cord-002542-f7l4ty2j 189 13 incorrect incorrect JJ cord-002542-f7l4ty2j 189 14 demultiplexing demultiplexing NN cord-002542-f7l4ty2j 189 15 of of IN cord-002542-f7l4ty2j 189 16 neighboring neighboring NN cord-002542-f7l4ty2j 189 17 samples sample NNS cord-002542-f7l4ty2j 189 18 on on IN cord-002542-f7l4ty2j 189 19 the the DT cord-002542-f7l4ty2j 189 20 HiSeq HiSeq NNP cord-002542-f7l4ty2j 189 21 flow flow NN cord-002542-f7l4ty2j 189 22 - - HYPH cord-002542-f7l4ty2j 189 23 cell cell NN cord-002542-f7l4ty2j 189 24 [ [ -LRB- cord-002542-f7l4ty2j 189 25 56 56 CD cord-002542-f7l4ty2j 189 26 ] ] -RRB- cord-002542-f7l4ty2j 189 27 or or CC cord-002542-f7l4ty2j 189 28 from from IN cord-002542-f7l4ty2j 189 29 contaminants contaminant NNS cord-002542-f7l4ty2j 189 30 in in IN cord-002542-f7l4ty2j 189 31 the the DT cord-002542-f7l4ty2j 189 32 RNAseq RNAseq NNP cord-002542-f7l4ty2j 189 33 library library NN cord-002542-f7l4ty2j 189 34 generation generation NN cord-002542-f7l4ty2j 189 35 [ [ -LRB- cord-002542-f7l4ty2j 189 36 57 57 CD cord-002542-f7l4ty2j 189 37 ] ] -RRB- cord-002542-f7l4ty2j 189 38 . . . cord-002542-f7l4ty2j 190 1 Having have VBG cord-002542-f7l4ty2j 190 2 accounted account VBN cord-002542-f7l4ty2j 190 3 for for IN cord-002542-f7l4ty2j 190 4 almost almost RB cord-002542-f7l4ty2j 190 5 all all DT cord-002542-f7l4ty2j 190 6 of of IN cord-002542-f7l4ty2j 190 7 the the DT cord-002542-f7l4ty2j 190 8 reads read NNS cord-002542-f7l4ty2j 190 9 present present JJ cord-002542-f7l4ty2j 190 10 in in IN cord-002542-f7l4ty2j 190 11 each each DT cord-002542-f7l4ty2j 190 12 dataset dataset NN cord-002542-f7l4ty2j 190 13 , , , cord-002542-f7l4ty2j 190 14 we -PRON- PRP cord-002542-f7l4ty2j 190 15 can can MD cord-002542-f7l4ty2j 190 16 be be VB cord-002542-f7l4ty2j 190 17 confident confident JJ cord-002542-f7l4ty2j 190 18 that that IN cord-002542-f7l4ty2j 190 19 we -PRON- PRP cord-002542-f7l4ty2j 190 20 are be VBP cord-002542-f7l4ty2j 190 21 capturing capture VBG cord-002542-f7l4ty2j 190 22 the the DT cord-002542-f7l4ty2j 190 23 full full JJ cord-002542-f7l4ty2j 190 24 range range NN cord-002542-f7l4ty2j 190 25 of of IN cord-002542-f7l4ty2j 190 26 recombination recombination NN cord-002542-f7l4ty2j 190 27 events event NNS cord-002542-f7l4ty2j 190 28 and/ and/ CD cord-002542-f7l4ty2j 190 29 or or CC cord-002542-f7l4ty2j 190 30 other other JJ cord-002542-f7l4ty2j 190 31 rearrangements rearrangement NNS cord-002542-f7l4ty2j 190 32 present present JJ cord-002542-f7l4ty2j 190 33 within within IN cord-002542-f7l4ty2j 190 34 each each DT cord-002542-f7l4ty2j 190 35 sample sample NN cord-002542-f7l4ty2j 190 36 and and CC cord-002542-f7l4ty2j 190 37 thus thus RB cord-002542-f7l4ty2j 190 38 are be VBP cord-002542-f7l4ty2j 190 39 not not RB cord-002542-f7l4ty2j 190 40 missing miss VBG cord-002542-f7l4ty2j 190 41 important important JJ cord-002542-f7l4ty2j 190 42 or or CC cord-002542-f7l4ty2j 190 43 significant significant JJ cord-002542-f7l4ty2j 190 44 events event NNS cord-002542-f7l4ty2j 190 45 due due IN cord-002542-f7l4ty2j 190 46 to to IN cord-002542-f7l4ty2j 190 47 computational computational JJ cord-002542-f7l4ty2j 190 48 limitations limitation NNS cord-002542-f7l4ty2j 190 49 . . . cord-002542-f7l4ty2j 191 1 To to TO cord-002542-f7l4ty2j 191 2 demonstrate demonstrate VB cord-002542-f7l4ty2j 191 3 the the DT cord-002542-f7l4ty2j 191 4 reproducibility reproducibility NN cord-002542-f7l4ty2j 191 5 of of IN cord-002542-f7l4ty2j 191 6 the the DT cord-002542-f7l4ty2j 191 7 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 191 8 approach approach NN cord-002542-f7l4ty2j 191 9 and and CC cord-002542-f7l4ty2j 191 10 to to TO cord-002542-f7l4ty2j 191 11 assess assess VB cord-002542-f7l4ty2j 191 12 the the DT cord-002542-f7l4ty2j 191 13 limit limit NN cord-002542-f7l4ty2j 191 14 in in IN cord-002542-f7l4ty2j 191 15 terms term NNS cord-002542-f7l4ty2j 191 16 of of IN cord-002542-f7l4ty2j 191 17 our -PRON- PRP$ cord-002542-f7l4ty2j 191 18 ability ability NN cord-002542-f7l4ty2j 191 19 to to TO cord-002542-f7l4ty2j 191 20 successfully successfully RB cord-002542-f7l4ty2j 191 21 detect detect VB cord-002542-f7l4ty2j 191 22 rare rare JJ cord-002542-f7l4ty2j 191 23 recombination recombination NN cord-002542-f7l4ty2j 191 24 events event NNS cord-002542-f7l4ty2j 191 25 , , , cord-002542-f7l4ty2j 191 26 we -PRON- PRP cord-002542-f7l4ty2j 191 27 generated generate VBD cord-002542-f7l4ty2j 191 28 three three CD cord-002542-f7l4ty2j 191 29 Virus virus NN cord-002542-f7l4ty2j 191 30 was be VBD cord-002542-f7l4ty2j 191 31 allowed allow VBN cord-002542-f7l4ty2j 191 32 to to TO cord-002542-f7l4ty2j 191 33 propagate propagate VB cord-002542-f7l4ty2j 191 34 for for IN cord-002542-f7l4ty2j 191 35 three three CD cord-002542-f7l4ty2j 191 36 days day NNS cord-002542-f7l4ty2j 191 37 after after IN cord-002542-f7l4ty2j 191 38 which which WDT cord-002542-f7l4ty2j 191 39 cells cell NNS cord-002542-f7l4ty2j 191 40 and and CC cord-002542-f7l4ty2j 191 41 the the DT cord-002542-f7l4ty2j 191 42 supernatant supernatant NN cord-002542-f7l4ty2j 191 43 were be VBD cord-002542-f7l4ty2j 191 44 collected collect VBN cord-002542-f7l4ty2j 191 45 . . . cord-002542-f7l4ty2j 192 1 A a DT cord-002542-f7l4ty2j 192 2 fraction fraction NN cord-002542-f7l4ty2j 192 3 ( ( -LRB- cord-002542-f7l4ty2j 192 4 1:10 1:10 CD cord-002542-f7l4ty2j 192 5 ) ) -RRB- cord-002542-f7l4ty2j 192 6 was be VBD cord-002542-f7l4ty2j 192 7 used use VBN cord-002542-f7l4ty2j 192 8 to to TO cord-002542-f7l4ty2j 192 9 further further RB cord-002542-f7l4ty2j 192 10 infect infect VB cord-002542-f7l4ty2j 192 11 a a DT cord-002542-f7l4ty2j 192 12 new new JJ cord-002542-f7l4ty2j 192 13 population population NN cord-002542-f7l4ty2j 192 14 of of IN cord-002542-f7l4ty2j 192 15 S2 s2 NN cord-002542-f7l4ty2j 192 16 cells cell NNS cord-002542-f7l4ty2j 192 17 in in IN cord-002542-f7l4ty2j 192 18 a a DT cord-002542-f7l4ty2j 192 19 series series NN cord-002542-f7l4ty2j 192 20 of of IN cord-002542-f7l4ty2j 192 21 passages passage NNS cord-002542-f7l4ty2j 192 22 . . . cord-002542-f7l4ty2j 193 1 The the DT cord-002542-f7l4ty2j 193 2 remaining remain VBG cord-002542-f7l4ty2j 193 3 fraction fraction NN cord-002542-f7l4ty2j 193 4 was be VBD cord-002542-f7l4ty2j 193 5 collected collect VBN cord-002542-f7l4ty2j 193 6 for for IN cord-002542-f7l4ty2j 193 7 analysis analysis NN cord-002542-f7l4ty2j 193 8 . . . cord-002542-f7l4ty2j 194 1 In in IN cord-002542-f7l4ty2j 194 2 total total NN cord-002542-f7l4ty2j 194 3 , , , cord-002542-f7l4ty2j 194 4 three three CD cord-002542-f7l4ty2j 194 5 replicates replicate NNS cord-002542-f7l4ty2j 194 6 of of IN cord-002542-f7l4ty2j 194 7 nine nine CD cord-002542-f7l4ty2j 194 8 passages passage NNS cord-002542-f7l4ty2j 194 9 were be VBD cord-002542-f7l4ty2j 194 10 collected collect VBN cord-002542-f7l4ty2j 194 11 . . . cord-002542-f7l4ty2j 195 1 replicate replicate VB cord-002542-f7l4ty2j 195 2 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 195 3 libraries library NNS cord-002542-f7l4ty2j 195 4 from from IN cord-002542-f7l4ty2j 195 5 the the DT cord-002542-f7l4ty2j 195 6 RNA RNA NNP cord-002542-f7l4ty2j 195 7 sample sample NN cord-002542-f7l4ty2j 195 8 P7R2 P7R2 NNP cord-002542-f7l4ty2j 195 9 , , , cord-002542-f7l4ty2j 195 10 obtained obtain VBD cord-002542-f7l4ty2j 195 11 1x150bp 1x150bp CD cord-002542-f7l4ty2j 195 12 reads read NNS cord-002542-f7l4ty2j 195 13 and and CC cord-002542-f7l4ty2j 195 14 performed perform VBD cord-002542-f7l4ty2j 195 15 the the DT cord-002542-f7l4ty2j 195 16 same same JJ cord-002542-f7l4ty2j 195 17 computational computational JJ cord-002542-f7l4ty2j 195 18 analyses analysis NNS cord-002542-f7l4ty2j 195 19 as as IN cord-002542-f7l4ty2j 195 20 described describe VBN cord-002542-f7l4ty2j 195 21 above above RB cord-002542-f7l4ty2j 195 22 . . . cord-002542-f7l4ty2j 196 1 We -PRON- PRP cord-002542-f7l4ty2j 196 2 mapped map VBD cord-002542-f7l4ty2j 196 3 0.83 0.83 CD cord-002542-f7l4ty2j 196 4 M M NNP cord-002542-f7l4ty2j 196 5 , , , cord-002542-f7l4ty2j 196 6 1.45 1.45 CD cord-002542-f7l4ty2j 196 7 M M NNP cord-002542-f7l4ty2j 196 8 and and CC cord-002542-f7l4ty2j 196 9 1.18 1.18 CD cord-002542-f7l4ty2j 196 10 M M NNP cord-002542-f7l4ty2j 196 11 reads read VBZ cord-002542-f7l4ty2j 196 12 per per IN cord-002542-f7l4ty2j 196 13 library library NN cord-002542-f7l4ty2j 196 14 , , , cord-002542-f7l4ty2j 196 15 giving give VBG cord-002542-f7l4ty2j 196 16 an an DT cord-002542-f7l4ty2j 196 17 approximate approximate JJ cord-002542-f7l4ty2j 196 18 coverage coverage NN cord-002542-f7l4ty2j 196 19 of~42,000 of~42,000 CD cord-002542-f7l4ty2j 196 20 - - HYPH cord-002542-f7l4ty2j 196 21 139,000x 139,000x CD cord-002542-f7l4ty2j 196 22 coverage coverage NN cord-002542-f7l4ty2j 196 23 over over IN cord-002542-f7l4ty2j 196 24 FHV FHV NNP cord-002542-f7l4ty2j 196 25 RNA1 RNA1 NNP cord-002542-f7l4ty2j 197 1 and~18,000 and~18,000 LS cord-002542-f7l4ty2j 197 2 - - . cord-002542-f7l4ty2j 197 3 67,000x 67,000x . cord-002542-f7l4ty2j 198 1 over over IN cord-002542-f7l4ty2j 198 2 FHV FHV NNP cord-002542-f7l4ty2j 198 3 RNA2 RNA2 NNP cord-002542-f7l4ty2j 198 4 ( ( -LRB- cord-002542-f7l4ty2j 198 5 calculated calculate VBN cord-002542-f7l4ty2j 198 6 from from IN cord-002542-f7l4ty2j 198 7 the the DT cord-002542-f7l4ty2j 198 8 average average JJ cord-002542-f7l4ty2j 198 9 coverage coverage NN cord-002542-f7l4ty2j 198 10 over over IN cord-002542-f7l4ty2j 198 11 the the DT cord-002542-f7l4ty2j 198 12 conserved conserve VBN cord-002542-f7l4ty2j 198 13 5 5 CD cord-002542-f7l4ty2j 198 14 ' ' '' cord-002542-f7l4ty2j 198 15 and and CC cord-002542-f7l4ty2j 198 16 3 3 CD cord-002542-f7l4ty2j 198 17 ' ' POS cord-002542-f7l4ty2j 198 18 ends end NNS cord-002542-f7l4ty2j 198 19 ) ) -RRB- cord-002542-f7l4ty2j 198 20 . . . cord-002542-f7l4ty2j 199 1 When when WRB cord-002542-f7l4ty2j 199 2 comparing compare VBG cord-002542-f7l4ty2j 199 3 the the DT cord-002542-f7l4ty2j 199 4 frequency frequency NN cord-002542-f7l4ty2j 199 5 of of IN cord-002542-f7l4ty2j 199 6 unique unique JJ cord-002542-f7l4ty2j 199 7 recombination recombination NN cord-002542-f7l4ty2j 199 8 events event NNS cord-002542-f7l4ty2j 199 9 in in IN cord-002542-f7l4ty2j 199 10 either either DT cord-002542-f7l4ty2j 199 11 RNA1 RNA1 NNP cord-002542-f7l4ty2j 199 12 or or CC cord-002542-f7l4ty2j 199 13 RNA2 RNA2 NNP cord-002542-f7l4ty2j 199 14 between between IN cord-002542-f7l4ty2j 199 15 any any DT cord-002542-f7l4ty2j 199 16 pair pair NN cord-002542-f7l4ty2j 199 17 of of IN cord-002542-f7l4ty2j 199 18 the the DT cord-002542-f7l4ty2j 199 19 three three CD cord-002542-f7l4ty2j 199 20 replicates replicate NNS cord-002542-f7l4ty2j 199 21 , , , cord-002542-f7l4ty2j 199 22 we -PRON- PRP cord-002542-f7l4ty2j 199 23 find find VBP cord-002542-f7l4ty2j 199 24 excellent excellent JJ cord-002542-f7l4ty2j 199 25 correlation correlation NN cord-002542-f7l4ty2j 199 26 ( ( -LRB- cord-002542-f7l4ty2j 199 27 Pearson Pearson NNP cord-002542-f7l4ty2j 199 28 > > XX cord-002542-f7l4ty2j 199 29 0.99 0.99 CD cord-002542-f7l4ty2j 199 30 ) ) -RRB- cord-002542-f7l4ty2j 199 31 even even RB cord-002542-f7l4ty2j 199 32 for for IN cord-002542-f7l4ty2j 199 33 very very RB cord-002542-f7l4ty2j 199 34 infrequent infrequent JJ cord-002542-f7l4ty2j 199 35 recombination recombination NN cord-002542-f7l4ty2j 199 36 events event NNS cord-002542-f7l4ty2j 199 37 , , , cord-002542-f7l4ty2j 199 38 as as IN cord-002542-f7l4ty2j 199 39 illustrated illustrate VBN cord-002542-f7l4ty2j 199 40 in in IN cord-002542-f7l4ty2j 199 41 the the DT cord-002542-f7l4ty2j 199 42 scatter scatter NN cord-002542-f7l4ty2j 199 43 plots plot NNS cord-002542-f7l4ty2j 199 44 in in IN cord-002542-f7l4ty2j 199 45 S2 S2 NNP cord-002542-f7l4ty2j 199 46 Fig Fig NNP cord-002542-f7l4ty2j 199 47 . . . cord-002542-f7l4ty2j 200 1 Events event NNS cord-002542-f7l4ty2j 200 2 that that WDT cord-002542-f7l4ty2j 200 3 were be VBD cord-002542-f7l4ty2j 200 4 found find VBN cord-002542-f7l4ty2j 200 5 in in IN cord-002542-f7l4ty2j 200 6 two two CD cord-002542-f7l4ty2j 200 7 replicates replicate NNS cord-002542-f7l4ty2j 200 8 but but CC cord-002542-f7l4ty2j 200 9 not not RB cord-002542-f7l4ty2j 200 10 a a DT cord-002542-f7l4ty2j 200 11 third third JJ cord-002542-f7l4ty2j 200 12 , , , cord-002542-f7l4ty2j 200 13 never never RB cord-002542-f7l4ty2j 200 14 exceeded exceed VBD cord-002542-f7l4ty2j 200 15 more more JJR cord-002542-f7l4ty2j 200 16 than than IN cord-002542-f7l4ty2j 200 17 20 20 CD cord-002542-f7l4ty2j 200 18 mapped map VBN cord-002542-f7l4ty2j 200 19 reads read NNS cord-002542-f7l4ty2j 200 20 for for IN cord-002542-f7l4ty2j 200 21 RNA1 RNA1 NNP cord-002542-f7l4ty2j 200 22 and and CC cord-002542-f7l4ty2j 200 23 8 8 CD cord-002542-f7l4ty2j 200 24 reads read NNS cord-002542-f7l4ty2j 200 25 for for IN cord-002542-f7l4ty2j 200 26 RNA2 RNA2 NNP cord-002542-f7l4ty2j 200 27 . . . cord-002542-f7l4ty2j 201 1 If if IN cord-002542-f7l4ty2j 201 2 we -PRON- PRP cord-002542-f7l4ty2j 201 3 take take VBP cord-002542-f7l4ty2j 201 4 these these DT cord-002542-f7l4ty2j 201 5 values value NNS cord-002542-f7l4ty2j 201 6 as as IN cord-002542-f7l4ty2j 201 7 a a DT cord-002542-f7l4ty2j 201 8 cut cut NN cord-002542-f7l4ty2j 201 9 - - HYPH cord-002542-f7l4ty2j 201 10 offs off NNS cord-002542-f7l4ty2j 201 11 , , , cord-002542-f7l4ty2j 201 12 below below IN cord-002542-f7l4ty2j 201 13 which which WDT cord-002542-f7l4ty2j 201 14 we -PRON- PRP cord-002542-f7l4ty2j 201 15 begin begin VBP cord-002542-f7l4ty2j 201 16 to to TO cord-002542-f7l4ty2j 201 17 fail fail VB cord-002542-f7l4ty2j 201 18 to to TO cord-002542-f7l4ty2j 201 19 detect detect VB cord-002542-f7l4ty2j 201 20 events event NNS cord-002542-f7l4ty2j 201 21 , , , cord-002542-f7l4ty2j 201 22 then then RB cord-002542-f7l4ty2j 201 23 we -PRON- PRP cord-002542-f7l4ty2j 201 24 can can MD cord-002542-f7l4ty2j 201 25 conservatively conservatively RB cord-002542-f7l4ty2j 201 26 estimate estimate VB cord-002542-f7l4ty2j 201 27 that that IN cord-002542-f7l4ty2j 201 28 we -PRON- PRP cord-002542-f7l4ty2j 201 29 are be VBP cord-002542-f7l4ty2j 201 30 reproducibly reproducibly RB cord-002542-f7l4ty2j 201 31 sensitive sensitive JJ cord-002542-f7l4ty2j 201 32 to to IN cord-002542-f7l4ty2j 201 33 recombinant recombinant JJ cord-002542-f7l4ty2j 201 34 species specie NNS cord-002542-f7l4ty2j 201 35 that that WDT cord-002542-f7l4ty2j 201 36 are be VBP cord-002542-f7l4ty2j 201 37 present present JJ cord-002542-f7l4ty2j 201 38 at at IN cord-002542-f7l4ty2j 201 39 approximately approximately RB cord-002542-f7l4ty2j 201 40 0.048 0.048 CD cord-002542-f7l4ty2j 201 41 % % NN cord-002542-f7l4ty2j 201 42 ( ( -LRB- cord-002542-f7l4ty2j 201 43 20/ 20/ CD cord-002542-f7l4ty2j 201 44 42,000 42,000 CD cord-002542-f7l4ty2j 201 45 ) ) -RRB- cord-002542-f7l4ty2j 201 46 of of IN cord-002542-f7l4ty2j 201 47 RNA1 RNA1 NNP cord-002542-f7l4ty2j 201 48 population population NN cord-002542-f7l4ty2j 201 49 and and CC cord-002542-f7l4ty2j 201 50 0.044 0.044 CD cord-002542-f7l4ty2j 201 51 % % NN cord-002542-f7l4ty2j 201 52 ( ( -LRB- cord-002542-f7l4ty2j 201 53 8/18,000 8/18,000 CD cord-002542-f7l4ty2j 201 54 ) ) -RRB- cord-002542-f7l4ty2j 201 55 of of IN cord-002542-f7l4ty2j 201 56 the the DT cord-002542-f7l4ty2j 201 57 total total JJ cord-002542-f7l4ty2j 201 58 RNA2 RNA2 NNP cord-002542-f7l4ty2j 201 59 population population NN cord-002542-f7l4ty2j 201 60 when when WRB cord-002542-f7l4ty2j 201 61 obtaining~1 obtaining~1 NNP cord-002542-f7l4ty2j 201 62 M M NNP cord-002542-f7l4ty2j 201 63 sequence sequence NN cord-002542-f7l4ty2j 201 64 reads read VBZ cord-002542-f7l4ty2j 201 65 . . . cord-002542-f7l4ty2j 202 1 In in IN cord-002542-f7l4ty2j 202 2 the the DT cord-002542-f7l4ty2j 202 3 inoculum inoculum NN cord-002542-f7l4ty2j 202 4 ( ( -LRB- cord-002542-f7l4ty2j 202 5 P0 p0 NN cord-002542-f7l4ty2j 202 6 ) ) -RRB- cord-002542-f7l4ty2j 202 7 , , , cord-002542-f7l4ty2j 202 8 less less JJR cord-002542-f7l4ty2j 202 9 than than IN cord-002542-f7l4ty2j 202 10 0.2 0.2 CD cord-002542-f7l4ty2j 202 11 % % NN cord-002542-f7l4ty2j 202 12 of of IN cord-002542-f7l4ty2j 202 13 the the DT cord-002542-f7l4ty2j 202 14 all all PDT cord-002542-f7l4ty2j 202 15 the the DT cord-002542-f7l4ty2j 202 16 reads read NNS cord-002542-f7l4ty2j 202 17 mapped map VBN cord-002542-f7l4ty2j 202 18 to to IN cord-002542-f7l4ty2j 202 19 recombination recombination NN cord-002542-f7l4ty2j 202 20 events event NNS cord-002542-f7l4ty2j 202 21 ( ( -LRB- cord-002542-f7l4ty2j 202 22 Table table NN cord-002542-f7l4ty2j 202 23 1 1 CD cord-002542-f7l4ty2j 202 24 , , , cord-002542-f7l4ty2j 202 25 Fig Fig NNP cord-002542-f7l4ty2j 202 26 2A 2a CD cord-002542-f7l4ty2j 202 27 ) ) -RRB- cord-002542-f7l4ty2j 202 28 . . . cord-002542-f7l4ty2j 203 1 Inspection inspection NN cord-002542-f7l4ty2j 203 2 of of IN cord-002542-f7l4ty2j 203 3 these these DT cord-002542-f7l4ty2j 203 4 events event NNS cord-002542-f7l4ty2j 203 5 reveals reveal VBZ cord-002542-f7l4ty2j 203 6 that that IN cord-002542-f7l4ty2j 203 7 they -PRON- PRP cord-002542-f7l4ty2j 203 8 are be VBP cord-002542-f7l4ty2j 203 9 dispersed disperse VBN cord-002542-f7l4ty2j 203 10 throughout throughout IN cord-002542-f7l4ty2j 203 11 each each DT cord-002542-f7l4ty2j 203 12 of of IN cord-002542-f7l4ty2j 203 13 the the DT cord-002542-f7l4ty2j 203 14 genomic genomic JJ cord-002542-f7l4ty2j 203 15 RNAs rna NNS cord-002542-f7l4ty2j 203 16 . . . cord-002542-f7l4ty2j 204 1 RNA1 rna1 NN cord-002542-f7l4ty2j 204 2 recombination recombination NN cord-002542-f7l4ty2j 204 3 events event NNS cord-002542-f7l4ty2j 204 4 are be VBP cord-002542-f7l4ty2j 204 5 the the DT cord-002542-f7l4ty2j 204 6 least least RBS cord-002542-f7l4ty2j 204 7 frequent frequent JJ cord-002542-f7l4ty2j 204 8 , , , cord-002542-f7l4ty2j 204 9 with with IN cord-002542-f7l4ty2j 204 10 only only RB cord-002542-f7l4ty2j 204 11 22 22 CD cord-002542-f7l4ty2j 204 12 unique unique JJ cord-002542-f7l4ty2j 204 13 events event NNS cord-002542-f7l4ty2j 204 14 detected detect VBD cord-002542-f7l4ty2j 204 15 represented represent VBN cord-002542-f7l4ty2j 204 16 by by IN cord-002542-f7l4ty2j 204 17 2920 2920 CD cord-002542-f7l4ty2j 204 18 reads read NNS cord-002542-f7l4ty2j 204 19 and and CC cord-002542-f7l4ty2j 204 20 without without IN cord-002542-f7l4ty2j 204 21 an an DT cord-002542-f7l4ty2j 204 22 apparent apparent JJ cord-002542-f7l4ty2j 204 23 bias bias NN cord-002542-f7l4ty2j 204 24 toward toward IN cord-002542-f7l4ty2j 204 25 any any DT cord-002542-f7l4ty2j 204 26 specific specific JJ cord-002542-f7l4ty2j 204 27 location location NN cord-002542-f7l4ty2j 204 28 . . . cord-002542-f7l4ty2j 205 1 The the DT cord-002542-f7l4ty2j 205 2 three three CD cord-002542-f7l4ty2j 205 3 most most RBS cord-002542-f7l4ty2j 205 4 common common JJ cord-002542-f7l4ty2j 205 5 RNA1 RNA1 NNP cord-002542-f7l4ty2j 205 6 events event NNS cord-002542-f7l4ty2j 205 7 in in IN cord-002542-f7l4ty2j 205 8 the the DT cord-002542-f7l4ty2j 205 9 inoculum inoculum NN cord-002542-f7l4ty2j 205 10 are be VBP cord-002542-f7l4ty2j 205 11 2325 2325 CD cord-002542-f7l4ty2j 205 12 ^ ^ SYM cord-002542-f7l4ty2j 205 13 1241 1241 CD cord-002542-f7l4ty2j 205 14 , , , cord-002542-f7l4ty2j 205 15 1484 1484 CD cord-002542-f7l4ty2j 205 16 ^ ^ SYM cord-002542-f7l4ty2j 205 17 1944 1944 CD cord-002542-f7l4ty2j 205 18 , , , cord-002542-f7l4ty2j 205 19 and and CC cord-002542-f7l4ty2j 205 20 2199 2199 CD cord-002542-f7l4ty2j 205 21 ^ ^ SYM cord-002542-f7l4ty2j 205 22 393 393 CD cord-002542-f7l4ty2j 205 23 with with IN cord-002542-f7l4ty2j 205 24 514 514 CD cord-002542-f7l4ty2j 205 25 , , , cord-002542-f7l4ty2j 205 26 229 229 CD cord-002542-f7l4ty2j 205 27 , , , cord-002542-f7l4ty2j 205 28 and and CC cord-002542-f7l4ty2j 205 29 177 177 CD cord-002542-f7l4ty2j 205 30 mapped map VBD cord-002542-f7l4ty2j 205 31 reads read VBZ cord-002542-f7l4ty2j 205 32 respectively respectively RB cord-002542-f7l4ty2j 205 33 ( ( -LRB- cord-002542-f7l4ty2j 205 34 S1 S1 NNP cord-002542-f7l4ty2j 205 35 Datafile Datafile NNP cord-002542-f7l4ty2j 205 36 ) ) -RRB- cord-002542-f7l4ty2j 205 37 . . . cord-002542-f7l4ty2j 206 1 Read read VB cord-002542-f7l4ty2j 206 2 depth depth NN cord-002542-f7l4ty2j 206 3 for for IN cord-002542-f7l4ty2j 206 4 the the DT cord-002542-f7l4ty2j 206 5 wild wild JJ cord-002542-f7l4ty2j 206 6 - - HYPH cord-002542-f7l4ty2j 206 7 type type NN cord-002542-f7l4ty2j 206 8 genome genome NN cord-002542-f7l4ty2j 206 9 at at IN cord-002542-f7l4ty2j 206 10 these these DT cord-002542-f7l4ty2j 206 11 loci locus NNS cord-002542-f7l4ty2j 206 12 ranges range VBZ cord-002542-f7l4ty2j 206 13 from from IN cord-002542-f7l4ty2j 206 14 400 400 CD cord-002542-f7l4ty2j 206 15 K K NNP cord-002542-f7l4ty2j 206 16 to to IN cord-002542-f7l4ty2j 206 17 1.9 1.9 CD cord-002542-f7l4ty2j 206 18 M M NNP cord-002542-f7l4ty2j 206 19 reads read NNS cord-002542-f7l4ty2j 206 20 , , , cord-002542-f7l4ty2j 206 21 therefore therefore RB cord-002542-f7l4ty2j 206 22 these these DT cord-002542-f7l4ty2j 206 23 recombination recombination NN cord-002542-f7l4ty2j 206 24 events event NNS cord-002542-f7l4ty2j 206 25 make make VBP cord-002542-f7l4ty2j 206 26 - - HYPH cord-002542-f7l4ty2j 206 27 up up NN cord-002542-f7l4ty2j 206 28 at at IN cord-002542-f7l4ty2j 206 29 less less JJR cord-002542-f7l4ty2j 206 30 than than IN cord-002542-f7l4ty2j 206 31 0.1 0.1 CD cord-002542-f7l4ty2j 206 32 % % NN cord-002542-f7l4ty2j 206 33 of of IN cord-002542-f7l4ty2j 206 34 the the DT cord-002542-f7l4ty2j 206 35 total total JJ cord-002542-f7l4ty2j 206 36 viral viral JJ cord-002542-f7l4ty2j 206 37 population population NN cord-002542-f7l4ty2j 206 38 . . . cord-002542-f7l4ty2j 207 1 These these DT cord-002542-f7l4ty2j 207 2 are be VBP cord-002542-f7l4ty2j 207 3 not not RB cord-002542-f7l4ty2j 207 4 the the DT cord-002542-f7l4ty2j 207 5 events event NNS cord-002542-f7l4ty2j 207 6 that that WDT cord-002542-f7l4ty2j 207 7 have have VBP cord-002542-f7l4ty2j 207 8 been be VBN cord-002542-f7l4ty2j 207 9 previously previously RB cord-002542-f7l4ty2j 207 10 reported report VBN cord-002542-f7l4ty2j 207 11 as as IN cord-002542-f7l4ty2j 207 12 forming form VBG cord-002542-f7l4ty2j 207 13 FHV FHV NNP cord-002542-f7l4ty2j 207 14 DI DI NNP cord-002542-f7l4ty2j 207 15 - - HYPH cord-002542-f7l4ty2j 207 16 RNAs rna NNS cord-002542-f7l4ty2j 207 17 , , , cord-002542-f7l4ty2j 207 18 moreover moreover RB cord-002542-f7l4ty2j 207 19 none none NN cord-002542-f7l4ty2j 207 20 of of IN cord-002542-f7l4ty2j 207 21 these these DT cord-002542-f7l4ty2j 207 22 events event NNS cord-002542-f7l4ty2j 207 23 are be VBP cord-002542-f7l4ty2j 207 24 observed observe VBN cord-002542-f7l4ty2j 207 25 again again RB cord-002542-f7l4ty2j 207 26 in in IN cord-002542-f7l4ty2j 207 27 subsequent subsequent JJ cord-002542-f7l4ty2j 207 28 passages passage NNS cord-002542-f7l4ty2j 207 29 , , , cord-002542-f7l4ty2j 207 30 perhaps perhaps RB cord-002542-f7l4ty2j 207 31 due due IN cord-002542-f7l4ty2j 207 32 to to IN cord-002542-f7l4ty2j 207 33 approaching approach VBG cord-002542-f7l4ty2j 207 34 the the DT cord-002542-f7l4ty2j 207 35 sensitivity sensitivity NN cord-002542-f7l4ty2j 207 36 of of IN cord-002542-f7l4ty2j 207 37 discovery discovery NN cord-002542-f7l4ty2j 207 38 limit limit NN cord-002542-f7l4ty2j 207 39 as as IN cord-002542-f7l4ty2j 207 40 described describe VBN cord-002542-f7l4ty2j 207 41 above above RB cord-002542-f7l4ty2j 207 42 . . . cord-002542-f7l4ty2j 208 1 However however RB cord-002542-f7l4ty2j 208 2 , , , cord-002542-f7l4ty2j 208 3 due due IN cord-002542-f7l4ty2j 208 4 to to IN cord-002542-f7l4ty2j 208 5 the the DT cord-002542-f7l4ty2j 208 6 low low JJ cord-002542-f7l4ty2j 208 7 - - HYPH cord-002542-f7l4ty2j 208 8 rate rate NN cord-002542-f7l4ty2j 208 9 of of IN cord-002542-f7l4ty2j 208 10 artifactual artifactual JJ cord-002542-f7l4ty2j 208 11 recombination recombination NN cord-002542-f7l4ty2j 208 12 of of IN cord-002542-f7l4ty2j 208 13 the the DT cord-002542-f7l4ty2j 208 14 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 208 15 approach approach NN cord-002542-f7l4ty2j 208 16 ( ( -LRB- cord-002542-f7l4ty2j 208 17 > > NFP cord-002542-f7l4ty2j 208 18 3 3 CD cord-002542-f7l4ty2j 208 19 events event NNS cord-002542-f7l4ty2j 208 20 per per IN cord-002542-f7l4ty2j 208 21 millions million NNS cord-002542-f7l4ty2j 208 22 reads read VBZ cord-002542-f7l4ty2j 208 23 [ [ -LRB- cord-002542-f7l4ty2j 208 24 35 35 CD cord-002542-f7l4ty2j 208 25 ] ] -RRB- cord-002542-f7l4ty2j 208 26 ) ) -RRB- cord-002542-f7l4ty2j 208 27 , , , cord-002542-f7l4ty2j 208 28 we -PRON- PRP cord-002542-f7l4ty2j 208 29 can can MD cord-002542-f7l4ty2j 208 30 be be VB cord-002542-f7l4ty2j 208 31 confident confident JJ cord-002542-f7l4ty2j 208 32 that that IN cord-002542-f7l4ty2j 208 33 these these DT cord-002542-f7l4ty2j 208 34 are be VBP cord-002542-f7l4ty2j 208 35 not not RB cord-002542-f7l4ty2j 208 36 sequencing sequence VBG cord-002542-f7l4ty2j 208 37 artifacts artifact NNS cord-002542-f7l4ty2j 208 38 [ [ -LRB- cord-002542-f7l4ty2j 208 39 35 35 CD cord-002542-f7l4ty2j 208 40 ] ] -RRB- cord-002542-f7l4ty2j 208 41 . . . cord-002542-f7l4ty2j 209 1 Therefore therefore RB cord-002542-f7l4ty2j 209 2 , , , cord-002542-f7l4ty2j 209 3 these these DT cord-002542-f7l4ty2j 209 4 events event NNS cord-002542-f7l4ty2j 209 5 likely likely RB cord-002542-f7l4ty2j 209 6 represent represent VBP cord-002542-f7l4ty2j 209 7 non non JJ cord-002542-f7l4ty2j 209 8 - - JJ cord-002542-f7l4ty2j 209 9 viable viable JJ cord-002542-f7l4ty2j 209 10 or or CC cord-002542-f7l4ty2j 209 11 transient transient JJ cord-002542-f7l4ty2j 209 12 recombination recombination NN cord-002542-f7l4ty2j 209 13 events event NNS cord-002542-f7l4ty2j 209 14 that that WDT cord-002542-f7l4ty2j 209 15 arose arise VBD cord-002542-f7l4ty2j 209 16 due due JJ cord-002542-f7l4ty2j 209 17 to to IN cord-002542-f7l4ty2j 209 18 stochastic stochastic JJ cord-002542-f7l4ty2j 209 19 non non JJ cord-002542-f7l4ty2j 209 20 - - JJ cord-002542-f7l4ty2j 209 21 homologous homologous JJ cord-002542-f7l4ty2j 209 22 recombination recombination NN cord-002542-f7l4ty2j 209 23 . . . cord-002542-f7l4ty2j 210 1 For for IN cord-002542-f7l4ty2j 210 2 RNA2 RNA2 NNP cord-002542-f7l4ty2j 210 3 in in IN cord-002542-f7l4ty2j 210 4 the the DT cord-002542-f7l4ty2j 210 5 inoculum inoculum NN cord-002542-f7l4ty2j 210 6 , , , cord-002542-f7l4ty2j 210 7 the the DT cord-002542-f7l4ty2j 210 8 three three CD cord-002542-f7l4ty2j 210 9 most most RBS cord-002542-f7l4ty2j 210 10 frequently frequently RB cord-002542-f7l4ty2j 210 11 observed observe VBD cord-002542-f7l4ty2j 210 12 events event NNS cord-002542-f7l4ty2j 210 13 were be VBD cord-002542-f7l4ty2j 210 14 738 738 CD cord-002542-f7l4ty2j 210 15 ^ ^ SYM cord-002542-f7l4ty2j 210 16 1219 1219 CD cord-002542-f7l4ty2j 210 17 , , , cord-002542-f7l4ty2j 210 18 738 738 CD cord-002542-f7l4ty2j 210 19 ^ ^ SYM cord-002542-f7l4ty2j 210 20 1222 1222 CD cord-002542-f7l4ty2j 210 21 and and CC cord-002542-f7l4ty2j 210 22 1024 1024 CD cord-002542-f7l4ty2j 210 23 ^ ^ SYM cord-002542-f7l4ty2j 210 24 1190 1190 CD cord-002542-f7l4ty2j 210 25 , , , cord-002542-f7l4ty2j 210 26 with with IN cord-002542-f7l4ty2j 210 27 9849 9849 CD cord-002542-f7l4ty2j 210 28 , , , cord-002542-f7l4ty2j 210 29 5237 5237 CD cord-002542-f7l4ty2j 210 30 , , , cord-002542-f7l4ty2j 210 31 and and CC cord-002542-f7l4ty2j 210 32 3673 3673 CD cord-002542-f7l4ty2j 210 33 mapped map VBN cord-002542-f7l4ty2j 210 34 reads read VBZ cord-002542-f7l4ty2j 210 35 respectively respectively RB cord-002542-f7l4ty2j 210 36 ( ( -LRB- cord-002542-f7l4ty2j 210 37 S1 S1 NNP cord-002542-f7l4ty2j 210 38 Datafile Datafile NNP cord-002542-f7l4ty2j 210 39 ) ) -RRB- cord-002542-f7l4ty2j 210 40 . . . cord-002542-f7l4ty2j 211 1 Fig Fig NNP cord-002542-f7l4ty2j 211 2 2A 2a CD cord-002542-f7l4ty2j 211 3 ) ) -RRB- cord-002542-f7l4ty2j 211 4 . . . cord-002542-f7l4ty2j 212 1 Again again RB cord-002542-f7l4ty2j 212 2 , , , cord-002542-f7l4ty2j 212 3 these these DT cord-002542-f7l4ty2j 212 4 occur occur VBP cord-002542-f7l4ty2j 212 5 throughout throughout IN cord-002542-f7l4ty2j 212 6 each each DT cord-002542-f7l4ty2j 212 7 of of IN cord-002542-f7l4ty2j 212 8 the the DT cord-002542-f7l4ty2j 212 9 genomic genomic JJ cord-002542-f7l4ty2j 212 10 RNAs rna NNS cord-002542-f7l4ty2j 212 11 . . . cord-002542-f7l4ty2j 213 1 However however RB cord-002542-f7l4ty2j 213 2 , , , cord-002542-f7l4ty2j 213 3 we -PRON- PRP cord-002542-f7l4ty2j 213 4 do do VBP cord-002542-f7l4ty2j 213 5 begin begin VB cord-002542-f7l4ty2j 213 6 to to TO cord-002542-f7l4ty2j 213 7 see see VB cord-002542-f7l4ty2j 213 8 events event NNS cord-002542-f7l4ty2j 213 9 that that WDT cord-002542-f7l4ty2j 213 10 have have VBP cord-002542-f7l4ty2j 213 11 previously previously RB cord-002542-f7l4ty2j 213 12 been be VBN cord-002542-f7l4ty2j 213 13 characterized characterize VBN cord-002542-f7l4ty2j 213 14 as as IN cord-002542-f7l4ty2j 213 15 forming form VBG cord-002542-f7l4ty2j 213 16 DI DI NNP cord-002542-f7l4ty2j 213 17 - - HYPH cord-002542-f7l4ty2j 213 18 RNAs rna NNS cord-002542-f7l4ty2j 213 19 , , , cord-002542-f7l4ty2j 213 20 such such JJ cord-002542-f7l4ty2j 213 21 as as IN cord-002542-f7l4ty2j 213 22 311 311 CD cord-002542-f7l4ty2j 213 23 ^ ^ SYM cord-002542-f7l4ty2j 213 24 1104 1104 CD cord-002542-f7l4ty2j 213 25 and and CC cord-002542-f7l4ty2j 213 26 301 301 CD cord-002542-f7l4ty2j 213 27 ^ ^ SYM cord-002542-f7l4ty2j 213 28 1100 1100 CD cord-002542-f7l4ty2j 213 29 , , , cord-002542-f7l4ty2j 213 30 although although IN cord-002542-f7l4ty2j 213 31 these these DT cord-002542-f7l4ty2j 213 32 events event NNS cord-002542-f7l4ty2j 213 33 are be VBP cord-002542-f7l4ty2j 213 34 present present JJ cord-002542-f7l4ty2j 213 35 at at IN cord-002542-f7l4ty2j 213 36 low low JJ cord-002542-f7l4ty2j 213 37 levels level NNS cord-002542-f7l4ty2j 213 38 ( ( -LRB- cord-002542-f7l4ty2j 213 39 70 70 CD cord-002542-f7l4ty2j 213 40 and and CC cord-002542-f7l4ty2j 213 41 21 21 CD cord-002542-f7l4ty2j 213 42 reads read NNS cord-002542-f7l4ty2j 213 43 in in IN cord-002542-f7l4ty2j 213 44 Replicate Replicate NNP cord-002542-f7l4ty2j 213 45 1 1 CD cord-002542-f7l4ty2j 213 46 from from IN cord-002542-f7l4ty2j 213 47 a a DT cord-002542-f7l4ty2j 213 48 total total NN cord-002542-f7l4ty2j 213 49 of of IN cord-002542-f7l4ty2j 213 50 8.2 8.2 CD cord-002542-f7l4ty2j 213 51 M M NNP cord-002542-f7l4ty2j 213 52 reads read VBZ cord-002542-f7l4ty2j 213 53 mapped map VBN cord-002542-f7l4ty2j 213 54 to to IN cord-002542-f7l4ty2j 213 55 the the DT cord-002542-f7l4ty2j 213 56 FHV FHV NNP cord-002542-f7l4ty2j 213 57 genome genome NN cord-002542-f7l4ty2j 213 58 ) ) -RRB- cord-002542-f7l4ty2j 214 1 ( ( -LRB- cord-002542-f7l4ty2j 214 2 S1 S1 NNP cord-002542-f7l4ty2j 214 3 Datafile Datafile NNP cord-002542-f7l4ty2j 214 4 ) ) -RRB- cord-002542-f7l4ty2j 214 5 . . . cord-002542-f7l4ty2j 215 1 In in IN cord-002542-f7l4ty2j 215 2 subsequent subsequent JJ cord-002542-f7l4ty2j 215 3 passages passage NNS cord-002542-f7l4ty2j 215 4 there there EX cord-002542-f7l4ty2j 215 5 was be VBD cord-002542-f7l4ty2j 215 6 a a DT cord-002542-f7l4ty2j 215 7 rapid rapid JJ cord-002542-f7l4ty2j 215 8 increase increase NN cord-002542-f7l4ty2j 215 9 in in IN cord-002542-f7l4ty2j 215 10 the the DT cord-002542-f7l4ty2j 215 11 total total JJ cord-002542-f7l4ty2j 215 12 proportion proportion NN cord-002542-f7l4ty2j 215 13 of of IN cord-002542-f7l4ty2j 215 14 mapped map VBN cord-002542-f7l4ty2j 215 15 recombination recombination NN cord-002542-f7l4ty2j 215 16 events event NNS cord-002542-f7l4ty2j 215 17 ( ( -LRB- cord-002542-f7l4ty2j 215 18 peaking peak VBG cord-002542-f7l4ty2j 215 19 at at IN cord-002542-f7l4ty2j 215 20 11.9 11.9 CD cord-002542-f7l4ty2j 215 21 % % NN cord-002542-f7l4ty2j 215 22 in in IN cord-002542-f7l4ty2j 215 23 P8R1 P8R1 NNP cord-002542-f7l4ty2j 215 24 ) ) -RRB- cord-002542-f7l4ty2j 216 1 ( ( -LRB- cord-002542-f7l4ty2j 216 2 Table table NN cord-002542-f7l4ty2j 216 3 1 1 CD cord-002542-f7l4ty2j 216 4 , , , cord-002542-f7l4ty2j 216 5 Fig Fig NNP cord-002542-f7l4ty2j 216 6 2A 2a CD cord-002542-f7l4ty2j 216 7 ) ) -RRB- cord-002542-f7l4ty2j 216 8 . . . cord-002542-f7l4ty2j 217 1 In in IN cord-002542-f7l4ty2j 217 2 these these DT cord-002542-f7l4ty2j 217 3 later later JJ cord-002542-f7l4ty2j 217 4 passages passage NNS cord-002542-f7l4ty2j 217 5 for for IN cord-002542-f7l4ty2j 217 6 each each DT cord-002542-f7l4ty2j 217 7 replicate replicate NN cord-002542-f7l4ty2j 217 8 , , , cord-002542-f7l4ty2j 217 9 it -PRON- PRP cord-002542-f7l4ty2j 217 10 can can MD cord-002542-f7l4ty2j 217 11 be be VB cord-002542-f7l4ty2j 217 12 seen see VBN cord-002542-f7l4ty2j 217 13 that that IN cord-002542-f7l4ty2j 217 14 the the DT cord-002542-f7l4ty2j 217 15 most most RBS cord-002542-f7l4ty2j 217 16 common common JJ cord-002542-f7l4ty2j 217 17 recombination recombination NN cord-002542-f7l4ty2j 217 18 events event NNS cord-002542-f7l4ty2j 217 19 are be VBP cord-002542-f7l4ty2j 217 20 deletions deletion NNS cord-002542-f7l4ty2j 217 21 that that WDT cord-002542-f7l4ty2j 217 22 span span VBP cord-002542-f7l4ty2j 217 23 two two CD cord-002542-f7l4ty2j 217 24 regions region NNS cord-002542-f7l4ty2j 217 25 in in IN cord-002542-f7l4ty2j 217 26 each each DT cord-002542-f7l4ty2j 217 27 genomic genomic JJ cord-002542-f7l4ty2j 217 28 RNA RNA NNP cord-002542-f7l4ty2j 217 29 including include VBG cord-002542-f7l4ty2j 217 30 : : : cord-002542-f7l4ty2j 217 31 nts nts NNP cord-002542-f7l4ty2j 217 32 300 300 CD cord-002542-f7l4ty2j 217 33 - - SYM cord-002542-f7l4ty2j 217 34 940 940 CD cord-002542-f7l4ty2j 217 35 and and CC cord-002542-f7l4ty2j 217 36 nts nts NNPS cord-002542-f7l4ty2j 217 37 1240 1240 CD cord-002542-f7l4ty2j 217 38 - - HYPH cord-002542-f7l4ty2j 217 39 2300 2300 CD cord-002542-f7l4ty2j 217 40 of of IN cord-002542-f7l4ty2j 217 41 RNA1 RNA1 NNP cord-002542-f7l4ty2j 217 42 ; ; : cord-002542-f7l4ty2j 217 43 and and CC cord-002542-f7l4ty2j 217 44 nts nts NNPS cord-002542-f7l4ty2j 217 45 250 250 CD cord-002542-f7l4ty2j 217 46 - - HYPH cord-002542-f7l4ty2j 217 47 510 510 CD cord-002542-f7l4ty2j 217 48 and and CC cord-002542-f7l4ty2j 217 49 nts nts NNPS cord-002542-f7l4ty2j 217 50 740 740 CD cord-002542-f7l4ty2j 217 51 - - HYPH cord-002542-f7l4ty2j 217 52 1220 1220 CD cord-002542-f7l4ty2j 217 53 of of IN cord-002542-f7l4ty2j 217 54 RNA2 RNA2 NNP cord-002542-f7l4ty2j 217 55 , , , cord-002542-f7l4ty2j 217 56 consistent consistent JJ cord-002542-f7l4ty2j 217 57 with with IN cord-002542-f7l4ty2j 217 58 previous previous JJ cord-002542-f7l4ty2j 217 59 observations observation NNS cord-002542-f7l4ty2j 217 60 of of IN cord-002542-f7l4ty2j 217 61 FHV FHV NNP cord-002542-f7l4ty2j 217 62 DI DI NNP cord-002542-f7l4ty2j 217 63 - - HYPH cord-002542-f7l4ty2j 217 64 RNAs rna NNS cord-002542-f7l4ty2j 217 65 [ [ -LRB- cord-002542-f7l4ty2j 217 66 31 31 CD cord-002542-f7l4ty2j 217 67 ] ] -RRB- cord-002542-f7l4ty2j 217 68 ( ( -LRB- cord-002542-f7l4ty2j 217 69 S1 S1 NNP cord-002542-f7l4ty2j 217 70 Datafile Datafile NNP cord-002542-f7l4ty2j 217 71 ) ) -RRB- cord-002542-f7l4ty2j 217 72 . . . cord-002542-f7l4ty2j 218 1 However however RB cord-002542-f7l4ty2j 218 2 , , , cord-002542-f7l4ty2j 218 3 the the DT cord-002542-f7l4ty2j 218 4 exact exact JJ cord-002542-f7l4ty2j 218 5 sites site NNS cord-002542-f7l4ty2j 218 6 of of IN cord-002542-f7l4ty2j 218 7 the the DT cord-002542-f7l4ty2j 218 8 recombination recombination NN cord-002542-f7l4ty2j 218 9 events event NNS cord-002542-f7l4ty2j 218 10 , , , cord-002542-f7l4ty2j 218 11 while while IN cord-002542-f7l4ty2j 218 12 repeatedly repeatedly RB cord-002542-f7l4ty2j 218 13 observed observe VBD cord-002542-f7l4ty2j 218 14 over over IN cord-002542-f7l4ty2j 218 15 time time NN cord-002542-f7l4ty2j 218 16 in in IN cord-002542-f7l4ty2j 218 17 each each DT cord-002542-f7l4ty2j 218 18 replicate replicate NN cord-002542-f7l4ty2j 218 19 , , , cord-002542-f7l4ty2j 218 20 varied varied JJ cord-002542-f7l4ty2j 218 21 between between IN cord-002542-f7l4ty2j 218 22 replicates replicate NNS cord-002542-f7l4ty2j 218 23 and and CC cord-002542-f7l4ty2j 218 24 each each DT cord-002542-f7l4ty2j 218 25 had have VBD cord-002542-f7l4ty2j 218 26 distinct distinct JJ cord-002542-f7l4ty2j 218 27 ' ' `` cord-002542-f7l4ty2j 218 28 most most RBS cord-002542-f7l4ty2j 218 29 popular popular JJ cord-002542-f7l4ty2j 218 30 ' ' `` cord-002542-f7l4ty2j 218 31 species specie NNS cord-002542-f7l4ty2j 218 32 in in IN cord-002542-f7l4ty2j 218 33 the the DT cord-002542-f7l4ty2j 218 34 final final JJ cord-002542-f7l4ty2j 218 35 passages passage NNS cord-002542-f7l4ty2j 218 36 ( ( -LRB- cord-002542-f7l4ty2j 218 37 Table table NN cord-002542-f7l4ty2j 218 38 2 2 CD cord-002542-f7l4ty2j 218 39 ) ) -RRB- cord-002542-f7l4ty2j 218 40 . . . cord-002542-f7l4ty2j 219 1 In in IN cord-002542-f7l4ty2j 219 2 some some DT cord-002542-f7l4ty2j 219 3 instances instance NNS cord-002542-f7l4ty2j 219 4 we -PRON- PRP cord-002542-f7l4ty2j 219 5 are be VBP cord-002542-f7l4ty2j 219 6 able able JJ cord-002542-f7l4ty2j 219 7 to to TO cord-002542-f7l4ty2j 219 8 find find VB cord-002542-f7l4ty2j 219 9 that that IN cord-002542-f7l4ty2j 219 10 a a DT cord-002542-f7l4ty2j 219 11 specific specific JJ cord-002542-f7l4ty2j 219 12 event event NN cord-002542-f7l4ty2j 219 13 is be VBZ cord-002542-f7l4ty2j 219 14 predominant predominant JJ cord-002542-f7l4ty2j 219 15 in in IN cord-002542-f7l4ty2j 219 16 one one CD cord-002542-f7l4ty2j 219 17 replicate replicate VB cord-002542-f7l4ty2j 219 18 while while IN cord-002542-f7l4ty2j 219 19 at at IN cord-002542-f7l4ty2j 219 20 low low JJ cord-002542-f7l4ty2j 219 21 levels level NNS cord-002542-f7l4ty2j 219 22 in in IN cord-002542-f7l4ty2j 219 23 another another DT cord-002542-f7l4ty2j 219 24 . . . cord-002542-f7l4ty2j 220 1 Overall overall RB cord-002542-f7l4ty2j 220 2 , , , cord-002542-f7l4ty2j 220 3 these these DT cord-002542-f7l4ty2j 220 4 trends trend NNS cord-002542-f7l4ty2j 220 5 in in IN cord-002542-f7l4ty2j 220 6 the the DT cord-002542-f7l4ty2j 220 7 frequency frequency NN cord-002542-f7l4ty2j 220 8 of of IN cord-002542-f7l4ty2j 220 9 recombination recombination NN cord-002542-f7l4ty2j 220 10 events event NNS cord-002542-f7l4ty2j 220 11 throughout throughout IN cord-002542-f7l4ty2j 220 12 passaging passaging NN cord-002542-f7l4ty2j 220 13 reveal reveal VBP cord-002542-f7l4ty2j 220 14 that that IN cord-002542-f7l4ty2j 220 15 once once RB cord-002542-f7l4ty2j 220 16 defective defective JJ cord-002542-f7l4ty2j 220 17 RNA RNA NNP cord-002542-f7l4ty2j 220 18 species specie NNS cord-002542-f7l4ty2j 220 19 emerge emerge VBP cord-002542-f7l4ty2j 220 20 during during IN cord-002542-f7l4ty2j 220 21 viral viral JJ cord-002542-f7l4ty2j 220 22 passaging passaging NN cord-002542-f7l4ty2j 220 23 they -PRON- PRP cord-002542-f7l4ty2j 220 24 rapidly rapidly RB cord-002542-f7l4ty2j 220 25 accumulate accumulate VBP cord-002542-f7l4ty2j 220 26 . . . cord-002542-f7l4ty2j 221 1 Despite despite IN cord-002542-f7l4ty2j 221 2 the the DT cord-002542-f7l4ty2j 221 3 predominance predominance NN cord-002542-f7l4ty2j 221 4 of of IN cord-002542-f7l4ty2j 221 5 certain certain JJ cord-002542-f7l4ty2j 221 6 recombination recombination NN cord-002542-f7l4ty2j 221 7 events event NNS cord-002542-f7l4ty2j 221 8 in in IN cord-002542-f7l4ty2j 221 9 the the DT cord-002542-f7l4ty2j 221 10 later later JJ cord-002542-f7l4ty2j 221 11 passages passage NNS cord-002542-f7l4ty2j 221 12 , , , cord-002542-f7l4ty2j 221 13 there there EX cord-002542-f7l4ty2j 221 14 still still RB cord-002542-f7l4ty2j 221 15 remained remain VBD cord-002542-f7l4ty2j 221 16 a a DT cord-002542-f7l4ty2j 221 17 large large JJ cord-002542-f7l4ty2j 221 18 number number NN cord-002542-f7l4ty2j 221 19 of of IN cord-002542-f7l4ty2j 221 20 infrequent infrequent JJ cord-002542-f7l4ty2j 221 21 events event NNS cord-002542-f7l4ty2j 221 22 scattered scatter VBN cord-002542-f7l4ty2j 221 23 throughout throughout IN cord-002542-f7l4ty2j 221 24 the the DT cord-002542-f7l4ty2j 221 25 viral viral JJ cord-002542-f7l4ty2j 221 26 genome genome NN cord-002542-f7l4ty2j 221 27 . . . cord-002542-f7l4ty2j 222 1 Many many JJ cord-002542-f7l4ty2j 222 2 of of IN cord-002542-f7l4ty2j 222 3 these these DT cord-002542-f7l4ty2j 222 4 are be VBP cord-002542-f7l4ty2j 222 5 observed observe VBN cord-002542-f7l4ty2j 222 6 only only RB cord-002542-f7l4ty2j 222 7 in in IN cord-002542-f7l4ty2j 222 8 one one CD cord-002542-f7l4ty2j 222 9 passage passage NN cord-002542-f7l4ty2j 222 10 and and CC cord-002542-f7l4ty2j 222 11 not not RB cord-002542-f7l4ty2j 222 12 in in IN cord-002542-f7l4ty2j 222 13 subsequent subsequent JJ cord-002542-f7l4ty2j 222 14 passages passage NNS cord-002542-f7l4ty2j 222 15 . . . cord-002542-f7l4ty2j 223 1 Again again RB cord-002542-f7l4ty2j 223 2 , , , cord-002542-f7l4ty2j 223 3 these these DT cord-002542-f7l4ty2j 223 4 events event NNS cord-002542-f7l4ty2j 223 5 likely likely RB cord-002542-f7l4ty2j 223 6 correspond correspond VBP cord-002542-f7l4ty2j 223 7 to to IN cord-002542-f7l4ty2j 223 8 stochastically stochastically RB cord-002542-f7l4ty2j 223 9 generated generate VBN cord-002542-f7l4ty2j 223 10 RNA RNA NNP cord-002542-f7l4ty2j 223 11 recombination recombination NN cord-002542-f7l4ty2j 223 12 events event NNS cord-002542-f7l4ty2j 223 13 that that WDT cord-002542-f7l4ty2j 223 14 form form VBP cord-002542-f7l4ty2j 223 15 non non JJ cord-002542-f7l4ty2j 223 16 - - JJ cord-002542-f7l4ty2j 223 17 viable viable JJ cord-002542-f7l4ty2j 223 18 defective defective JJ cord-002542-f7l4ty2j 223 19 RNAs rna NNS cord-002542-f7l4ty2j 223 20 . . . cord-002542-f7l4ty2j 224 1 We -PRON- PRP cord-002542-f7l4ty2j 224 2 reasoned reason VBD cord-002542-f7l4ty2j 224 3 that that IN cord-002542-f7l4ty2j 224 4 analyzing analyze VBG cord-002542-f7l4ty2j 224 5 these these DT cord-002542-f7l4ty2j 224 6 events event NNS cord-002542-f7l4ty2j 224 7 would would MD cord-002542-f7l4ty2j 224 8 more more RBR cord-002542-f7l4ty2j 224 9 accurately accurately RB cord-002542-f7l4ty2j 224 10 reveal reveal VB cord-002542-f7l4ty2j 224 11 the the DT cord-002542-f7l4ty2j 224 12 nucleotide nucleotide JJ cord-002542-f7l4ty2j 224 13 preference preference NN cord-002542-f7l4ty2j 224 14 of of IN cord-002542-f7l4ty2j 224 15 the the DT cord-002542-f7l4ty2j 224 16 FHV FHV NNP cord-002542-f7l4ty2j 224 17 RdRp RdRp NNP cord-002542-f7l4ty2j 224 18 for for IN cord-002542-f7l4ty2j 224 19 RNA RNA NNP cord-002542-f7l4ty2j 224 20 recombination recombination NN cord-002542-f7l4ty2j 224 21 as as IN cord-002542-f7l4ty2j 224 22 they -PRON- PRP cord-002542-f7l4ty2j 224 23 were be VBD cord-002542-f7l4ty2j 224 24 not not RB cord-002542-f7l4ty2j 224 25 subject subject JJ cord-002542-f7l4ty2j 224 26 to to IN cord-002542-f7l4ty2j 224 27 replicative replicative JJ cord-002542-f7l4ty2j 224 28 selection selection NN cord-002542-f7l4ty2j 224 29 ( ( -LRB- cord-002542-f7l4ty2j 224 30 although although IN cord-002542-f7l4ty2j 224 31 they -PRON- PRP cord-002542-f7l4ty2j 224 32 must must MD cord-002542-f7l4ty2j 224 33 be be VB cord-002542-f7l4ty2j 224 34 packaged package VBN cord-002542-f7l4ty2j 224 35 by by IN cord-002542-f7l4ty2j 224 36 FHV FHV NNP cord-002542-f7l4ty2j 224 37 particles particle NNS cord-002542-f7l4ty2j 224 38 ) ) -RRB- cord-002542-f7l4ty2j 224 39 , , , cord-002542-f7l4ty2j 224 40 unlike unlike IN cord-002542-f7l4ty2j 224 41 the the DT cord-002542-f7l4ty2j 224 42 DI DI NNP cord-002542-f7l4ty2j 224 43 - - HYPH cord-002542-f7l4ty2j 224 44 RNAs rna NNS cord-002542-f7l4ty2j 224 45 . . . cord-002542-f7l4ty2j 225 1 Therefore therefore RB cord-002542-f7l4ty2j 225 2 we -PRON- PRP cord-002542-f7l4ty2j 225 3 extracted extract VBD cord-002542-f7l4ty2j 225 4 all all DT cord-002542-f7l4ty2j 225 5 recombination recombination NN cord-002542-f7l4ty2j 225 6 events event NNS cord-002542-f7l4ty2j 225 7 occurring occur VBG cord-002542-f7l4ty2j 225 8 with with IN cord-002542-f7l4ty2j 225 9 fewer few JJR cord-002542-f7l4ty2j 225 10 than than IN cord-002542-f7l4ty2j 225 11 10 10 CD cord-002542-f7l4ty2j 225 12 mapped map VBN cord-002542-f7l4ty2j 225 13 reads read NNS cord-002542-f7l4ty2j 225 14 throughout throughout IN cord-002542-f7l4ty2j 225 15 all all DT cord-002542-f7l4ty2j 225 16 FHV FHV NNP cord-002542-f7l4ty2j 225 17 passages passage NNS cord-002542-f7l4ty2j 225 18 and and CC cord-002542-f7l4ty2j 225 19 replicates replicate NNS cord-002542-f7l4ty2j 225 20 ( ( -LRB- cord-002542-f7l4ty2j 225 21 20'723 20'723 CD cord-002542-f7l4ty2j 225 22 unique unique JJ cord-002542-f7l4ty2j 225 23 events event NNS cord-002542-f7l4ty2j 225 24 from from IN cord-002542-f7l4ty2j 225 25 a a DT cord-002542-f7l4ty2j 225 26 total total NN cord-002542-f7l4ty2j 225 27 of of IN cord-002542-f7l4ty2j 225 28 11.6 11.6 CD cord-002542-f7l4ty2j 225 29 M m NN cord-002542-f7l4ty2j 225 30 possible possible JJ cord-002542-f7l4ty2j 225 31 permutations permutation NNS cord-002542-f7l4ty2j 225 32 [ [ -LRB- cord-002542-f7l4ty2j 225 33 8 8 CD cord-002542-f7l4ty2j 225 34 ] ] -RRB- cord-002542-f7l4ty2j 225 35 ) ) -RRB- cord-002542-f7l4ty2j 225 36 and and CC cord-002542-f7l4ty2j 225 37 counted count VBD cord-002542-f7l4ty2j 225 38 the the DT cord-002542-f7l4ty2j 225 39 frequency frequency NN cord-002542-f7l4ty2j 225 40 of of IN cord-002542-f7l4ty2j 225 41 nucleotides nucleotide NNS cord-002542-f7l4ty2j 225 42 found find VBN cord-002542-f7l4ty2j 225 43 both both CC cord-002542-f7l4ty2j 225 44 up up IN cord-002542-f7l4ty2j 225 45 and and CC cord-002542-f7l4ty2j 225 46 down down IN cord-002542-f7l4ty2j 225 47 - - HYPH cord-002542-f7l4ty2j 225 48 stream stream NN cord-002542-f7l4ty2j 225 49 of of IN cord-002542-f7l4ty2j 225 50 5 5 CD cord-002542-f7l4ty2j 225 51 ' ' '' cord-002542-f7l4ty2j 225 52 and and CC cord-002542-f7l4ty2j 225 53 3 3 CD cord-002542-f7l4ty2j 225 54 ' ' POS cord-002542-f7l4ty2j 225 55 recombination recombination NN cord-002542-f7l4ty2j 225 56 sites site NNS cord-002542-f7l4ty2j 225 57 in in IN cord-002542-f7l4ty2j 225 58 the the DT cord-002542-f7l4ty2j 225 59 reference reference NN cord-002542-f7l4ty2j 225 60 genome genome NN cord-002542-f7l4ty2j 225 61 . . . cord-002542-f7l4ty2j 226 1 As as IN cord-002542-f7l4ty2j 226 2 shown show VBN cord-002542-f7l4ty2j 226 3 in in IN cord-002542-f7l4ty2j 226 4 Fig Fig NNP cord-002542-f7l4ty2j 226 5 2C 2c NN cord-002542-f7l4ty2j 226 6 , , , cord-002542-f7l4ty2j 226 7 this this DT cord-002542-f7l4ty2j 226 8 revealed reveal VBD cord-002542-f7l4ty2j 226 9 a a DT cord-002542-f7l4ty2j 226 10 preference preference NN cord-002542-f7l4ty2j 226 11 for for IN cord-002542-f7l4ty2j 226 12 A A NNP cord-002542-f7l4ty2j 226 13 's 's POS cord-002542-f7l4ty2j 226 14 1 1 CD cord-002542-f7l4ty2j 226 15 - - SYM cord-002542-f7l4ty2j 226 16 3nts 3nts CD cord-002542-f7l4ty2j 226 17 downstream downstream NN cord-002542-f7l4ty2j 226 18 of of IN cord-002542-f7l4ty2j 226 19 5 5 CD cord-002542-f7l4ty2j 226 20 ' ' '' cord-002542-f7l4ty2j 226 21 sites site NNS cord-002542-f7l4ty2j 226 22 , , , cord-002542-f7l4ty2j 226 23 a a DT cord-002542-f7l4ty2j 226 24 preference preference NN cord-002542-f7l4ty2j 226 25 for for IN cord-002542-f7l4ty2j 226 26 U U NNP cord-002542-f7l4ty2j 226 27 's 's POS cord-002542-f7l4ty2j 226 28 1 1 CD cord-002542-f7l4ty2j 226 29 - - SYM cord-002542-f7l4ty2j 226 30 3nts 3nt NNS cord-002542-f7l4ty2j 226 31 upstream upstream RB cord-002542-f7l4ty2j 226 32 of of IN cord-002542-f7l4ty2j 226 33 5 5 CD cord-002542-f7l4ty2j 226 34 ' ' '' cord-002542-f7l4ty2j 226 35 sites site NNS cord-002542-f7l4ty2j 226 36 , , , cord-002542-f7l4ty2j 226 37 a a DT cord-002542-f7l4ty2j 226 38 weaker weak JJR cord-002542-f7l4ty2j 226 39 preference preference NN cord-002542-f7l4ty2j 226 40 for for IN cord-002542-f7l4ty2j 226 41 a a DT cord-002542-f7l4ty2j 226 42 C c NN cord-002542-f7l4ty2j 226 43 1nt 1nt NN cord-002542-f7l4ty2j 226 44 up up IN cord-002542-f7l4ty2j 226 45 stream stream NN cord-002542-f7l4ty2j 226 46 of of IN cord-002542-f7l4ty2j 226 47 5 5 CD cord-002542-f7l4ty2j 226 48 ' ' '' cord-002542-f7l4ty2j 226 49 sites site NNS cord-002542-f7l4ty2j 226 50 , , , cord-002542-f7l4ty2j 226 51 and and CC cord-002542-f7l4ty2j 226 52 an an DT cord-002542-f7l4ty2j 226 53 aversion aversion NN cord-002542-f7l4ty2j 226 54 to to IN cord-002542-f7l4ty2j 226 55 G G NNP cord-002542-f7l4ty2j 226 56 's 's POS cord-002542-f7l4ty2j 226 57 2nts 2nts CD cord-002542-f7l4ty2j 226 58 both both CC cord-002542-f7l4ty2j 226 59 upstream upstream JJ cord-002542-f7l4ty2j 226 60 and and CC cord-002542-f7l4ty2j 226 61 downstream downstream RB cord-002542-f7l4ty2j 226 62 of of IN cord-002542-f7l4ty2j 226 63 5 5 CD cord-002542-f7l4ty2j 226 64 ' ' POS cord-002542-f7l4ty2j 226 65 sites site NNS cord-002542-f7l4ty2j 226 66 . . . cord-002542-f7l4ty2j 227 1 Interestingly interestingly RB cord-002542-f7l4ty2j 227 2 , , , cord-002542-f7l4ty2j 227 3 an an DT cord-002542-f7l4ty2j 227 4 almost almost RB cord-002542-f7l4ty2j 227 5 identical identical JJ cord-002542-f7l4ty2j 227 6 trend trend NN cord-002542-f7l4ty2j 227 7 was be VBD cord-002542-f7l4ty2j 227 8 observed observe VBN cord-002542-f7l4ty2j 227 9 for for IN cord-002542-f7l4ty2j 227 10 the the DT cord-002542-f7l4ty2j 227 11 3 3 CD cord-002542-f7l4ty2j 227 12 ' ' '' cord-002542-f7l4ty2j 227 13 sites site NNS cord-002542-f7l4ty2j 227 14 . . . cord-002542-f7l4ty2j 228 1 This this DT cord-002542-f7l4ty2j 228 2 trend trend NN cord-002542-f7l4ty2j 228 3 was be VBD cord-002542-f7l4ty2j 228 4 maintained maintain VBN cord-002542-f7l4ty2j 228 5 also also RB cord-002542-f7l4ty2j 228 6 when when WRB cord-002542-f7l4ty2j 228 7 analyzing analyze VBG cord-002542-f7l4ty2j 228 8 only only RB cord-002542-f7l4ty2j 228 9 recombination recombination NN cord-002542-f7l4ty2j 228 10 events event NNS cord-002542-f7l4ty2j 228 11 without without IN cord-002542-f7l4ty2j 228 12 ambiguity ambiguity NN cord-002542-f7l4ty2j 228 13 Pathways pathway NNS cord-002542-f7l4ty2j 228 14 of of IN cord-002542-f7l4ty2j 228 15 FHV FHV NNP cord-002542-f7l4ty2j 228 16 defective defective JJ cord-002542-f7l4ty2j 228 17 RNA RNA NNP cord-002542-f7l4ty2j 228 18 evolution evolution NN cord-002542-f7l4ty2j 228 19 by by IN cord-002542-f7l4ty2j 228 20 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 228 21 and and CC cord-002542-f7l4ty2j 228 22 the the DT cord-002542-f7l4ty2j 228 23 MinION MinION NNS cord-002542-f7l4ty2j 228 24 in in IN cord-002542-f7l4ty2j 228 25 the the DT cord-002542-f7l4ty2j 228 26 site site NN cord-002542-f7l4ty2j 228 27 of of IN cord-002542-f7l4ty2j 228 28 recombination recombination NN cord-002542-f7l4ty2j 228 29 ( ( -LRB- cord-002542-f7l4ty2j 228 30 i.e. i.e. FW cord-002542-f7l4ty2j 228 31 sites site NNS cord-002542-f7l4ty2j 228 32 that that WDT cord-002542-f7l4ty2j 228 33 lacked lack VBD cord-002542-f7l4ty2j 228 34 ' ' `` cord-002542-f7l4ty2j 228 35 fuzziness fuzziness NN cord-002542-f7l4ty2j 228 36 ' ' '' cord-002542-f7l4ty2j 228 37 as as IN cord-002542-f7l4ty2j 228 38 reported report VBN cord-002542-f7l4ty2j 228 39 by by IN cord-002542-f7l4ty2j 228 40 the the DT cord-002542-f7l4ty2j 228 41 ViReMa ViReMa NNP cord-002542-f7l4ty2j 228 42 pipeline pipeline NN cord-002542-f7l4ty2j 228 43 [ [ -LRB- cord-002542-f7l4ty2j 228 44 32 32 CD cord-002542-f7l4ty2j 228 45 ] ] -RRB- cord-002542-f7l4ty2j 228 46 ) ) -RRB- cord-002542-f7l4ty2j 228 47 . . . cord-002542-f7l4ty2j 229 1 This this DT cord-002542-f7l4ty2j 229 2 result result NN cord-002542-f7l4ty2j 229 3 is be VBZ cord-002542-f7l4ty2j 229 4 similar similar JJ cord-002542-f7l4ty2j 229 5 to to IN cord-002542-f7l4ty2j 229 6 what what WP cord-002542-f7l4ty2j 229 7 we -PRON- PRP cord-002542-f7l4ty2j 229 8 have have VBP cord-002542-f7l4ty2j 229 9 previously previously RB cord-002542-f7l4ty2j 229 10 reported report VBN cord-002542-f7l4ty2j 229 11 [ [ -LRB- cord-002542-f7l4ty2j 229 12 8 8 CD cord-002542-f7l4ty2j 229 13 ] ] -RRB- cord-002542-f7l4ty2j 229 14 . . . cord-002542-f7l4ty2j 230 1 However however RB cord-002542-f7l4ty2j 230 2 , , , cord-002542-f7l4ty2j 230 3 here here RB cord-002542-f7l4ty2j 230 4 we -PRON- PRP cord-002542-f7l4ty2j 230 5 provide provide VBP cord-002542-f7l4ty2j 230 6 a a DT cord-002542-f7l4ty2j 230 7 much much RB cord-002542-f7l4ty2j 230 8 larger large JJR cord-002542-f7l4ty2j 230 9 dataset dataset NN cord-002542-f7l4ty2j 230 10 and and CC cord-002542-f7l4ty2j 230 11 analyze analyze VB cord-002542-f7l4ty2j 230 12 events event NNS cord-002542-f7l4ty2j 230 13 that that WDT cord-002542-f7l4ty2j 230 14 we -PRON- PRP cord-002542-f7l4ty2j 230 15 can can MD cord-002542-f7l4ty2j 230 16 determine determine VB cord-002542-f7l4ty2j 230 17 are be VBP cord-002542-f7l4ty2j 230 18 not not RB cord-002542-f7l4ty2j 230 19 amplified amplify VBN cord-002542-f7l4ty2j 230 20 in in IN cord-002542-f7l4ty2j 230 21 subsequent subsequent JJ cord-002542-f7l4ty2j 230 22 passages passage NNS cord-002542-f7l4ty2j 230 23 , , , cord-002542-f7l4ty2j 230 24 providing provide VBG cord-002542-f7l4ty2j 230 25 greater great JJR cord-002542-f7l4ty2j 230 26 confidence confidence NN cord-002542-f7l4ty2j 230 27 that that IN cord-002542-f7l4ty2j 230 28 these these DT cord-002542-f7l4ty2j 230 29 sites site NNS cord-002542-f7l4ty2j 230 30 reflect reflect VBP cord-002542-f7l4ty2j 230 31 the the DT cord-002542-f7l4ty2j 230 32 preference preference NN cord-002542-f7l4ty2j 230 33 for for IN cord-002542-f7l4ty2j 230 34 RNA RNA NNP cord-002542-f7l4ty2j 230 35 recombination recombination NN cord-002542-f7l4ty2j 230 36 at at IN cord-002542-f7l4ty2j 230 37 these these DT cord-002542-f7l4ty2j 230 38 sites site NNS cord-002542-f7l4ty2j 230 39 rather rather RB cord-002542-f7l4ty2j 230 40 than than IN cord-002542-f7l4ty2j 230 41 the the DT cord-002542-f7l4ty2j 230 42 selection selection NN cord-002542-f7l4ty2j 230 43 of of IN cord-002542-f7l4ty2j 230 44 replicatively replicatively RB cord-002542-f7l4ty2j 230 45 viable viable JJ cord-002542-f7l4ty2j 230 46 defective defective JJ cord-002542-f7l4ty2j 230 47 RNA RNA NNP cord-002542-f7l4ty2j 230 48 species specie NNS cord-002542-f7l4ty2j 230 49 . . . cord-002542-f7l4ty2j 231 1 Open open JJ cord-002542-f7l4ty2j 231 2 reading reading NN cord-002542-f7l4ty2j 231 3 frames frame NNS cord-002542-f7l4ty2j 231 4 are be VBP cord-002542-f7l4ty2j 231 5 maintained maintain VBN cord-002542-f7l4ty2j 231 6 in in IN cord-002542-f7l4ty2j 231 7 most most JJS cord-002542-f7l4ty2j 231 8 DI DI NNP cord-002542-f7l4ty2j 231 9 - - HYPH cord-002542-f7l4ty2j 231 10 RNAs RNAs NNPS cord-002542-f7l4ty2j 232 1 Since since IN cord-002542-f7l4ty2j 232 2 many many JJ cord-002542-f7l4ty2j 232 3 recombination recombination NN cord-002542-f7l4ty2j 232 4 events event NNS cord-002542-f7l4ty2j 232 5 resulted result VBD cord-002542-f7l4ty2j 232 6 in in IN cord-002542-f7l4ty2j 232 7 deletions deletion NNS cord-002542-f7l4ty2j 232 8 of of IN cord-002542-f7l4ty2j 232 9 the the DT cord-002542-f7l4ty2j 232 10 viral viral JJ cord-002542-f7l4ty2j 232 11 genome genome NN cord-002542-f7l4ty2j 232 12 , , , cord-002542-f7l4ty2j 232 13 we -PRON- PRP cord-002542-f7l4ty2j 232 14 were be VBD cord-002542-f7l4ty2j 232 15 curious curious JJ cord-002542-f7l4ty2j 232 16 to to TO cord-002542-f7l4ty2j 232 17 see see VB cord-002542-f7l4ty2j 232 18 if if IN cord-002542-f7l4ty2j 232 19 the the DT cord-002542-f7l4ty2j 232 20 open open JJ cord-002542-f7l4ty2j 232 21 reading reading NN cord-002542-f7l4ty2j 232 22 frame frame NN cord-002542-f7l4ty2j 232 23 ( ( -LRB- cord-002542-f7l4ty2j 232 24 ORF ORF NNP cord-002542-f7l4ty2j 232 25 ) ) -RRB- cord-002542-f7l4ty2j 232 26 was be VBD cord-002542-f7l4ty2j 232 27 conserved conserve VBN cord-002542-f7l4ty2j 232 28 , , , cord-002542-f7l4ty2j 232 29 as as IN cord-002542-f7l4ty2j 232 30 conservation conservation NN cord-002542-f7l4ty2j 232 31 of of IN cord-002542-f7l4ty2j 232 32 an an DT cord-002542-f7l4ty2j 232 33 ORF ORF NNP cord-002542-f7l4ty2j 232 34 has have VBZ cord-002542-f7l4ty2j 232 35 frequently frequently RB cord-002542-f7l4ty2j 232 36 been be VBN cord-002542-f7l4ty2j 232 37 observed observe VBN cord-002542-f7l4ty2j 232 38 to to TO cord-002542-f7l4ty2j 232 39 be be VB cord-002542-f7l4ty2j 232 40 a a DT cord-002542-f7l4ty2j 232 41 property property NN cord-002542-f7l4ty2j 232 42 of of IN cord-002542-f7l4ty2j 232 43 defective defective JJ cord-002542-f7l4ty2j 232 44 and and CC cord-002542-f7l4ty2j 232 45 defective defective JJ cord-002542-f7l4ty2j 232 46 - - HYPH cord-002542-f7l4ty2j 232 47 interfering interfere VBG cord-002542-f7l4ty2j 232 48 RNAs rna NNS cord-002542-f7l4ty2j 232 49 [ [ -LRB- cord-002542-f7l4ty2j 232 50 58 58 CD cord-002542-f7l4ty2j 232 51 ] ] -RRB- cord-002542-f7l4ty2j 232 52 . . . cord-002542-f7l4ty2j 233 1 Moreover moreover RB cord-002542-f7l4ty2j 233 2 , , , cord-002542-f7l4ty2j 233 3 it -PRON- PRP cord-002542-f7l4ty2j 233 4 has have VBZ cord-002542-f7l4ty2j 233 5 previously previously RB cord-002542-f7l4ty2j 233 6 been be VBN cord-002542-f7l4ty2j 233 7 shown show VBN cord-002542-f7l4ty2j 233 8 that that IN cord-002542-f7l4ty2j 233 9 cloned clone VBN cord-002542-f7l4ty2j 233 10 DI DI NNP cord-002542-f7l4ty2j 233 11 - - HYPH cord-002542-f7l4ty2j 233 12 RNAs rna NNS cord-002542-f7l4ty2j 233 13 vectors vector NNS cord-002542-f7l4ty2j 233 14 containing contain VBG cord-002542-f7l4ty2j 233 15 eGPF egpf NN cord-002542-f7l4ty2j 233 16 in in IN cord-002542-f7l4ty2j 233 17 their -PRON- PRP$ cord-002542-f7l4ty2j 233 18 putative putative JJ cord-002542-f7l4ty2j 233 19 ORFs orf NNS cord-002542-f7l4ty2j 233 20 do do VBP cord-002542-f7l4ty2j 233 21 indeed indeed RB cord-002542-f7l4ty2j 233 22 express express VB cord-002542-f7l4ty2j 233 23 fluorescent fluorescent JJ cord-002542-f7l4ty2j 233 24 protein protein NN cord-002542-f7l4ty2j 233 25 [ [ -LRB- cord-002542-f7l4ty2j 233 26 59 59 CD cord-002542-f7l4ty2j 233 27 ] ] -RRB- cord-002542-f7l4ty2j 233 28 although although IN cord-002542-f7l4ty2j 233 29 it -PRON- PRP cord-002542-f7l4ty2j 233 30 is be VBZ cord-002542-f7l4ty2j 233 31 not not RB cord-002542-f7l4ty2j 233 32 clear clear JJ cord-002542-f7l4ty2j 233 33 whether whether IN cord-002542-f7l4ty2j 233 34 a a DT cord-002542-f7l4ty2j 233 35 functional functional JJ cord-002542-f7l4ty2j 233 36 ORF ORF NNP cord-002542-f7l4ty2j 233 37 is be VBZ cord-002542-f7l4ty2j 233 38 essential essential JJ cord-002542-f7l4ty2j 233 39 for for IN cord-002542-f7l4ty2j 233 40 DI DI NNP cord-002542-f7l4ty2j 233 41 - - HYPH cord-002542-f7l4ty2j 233 42 RNA RNA NNP cord-002542-f7l4ty2j 233 43 formation formation NN cord-002542-f7l4ty2j 233 44 or or CC cord-002542-f7l4ty2j 233 45 propagation propagation NN cord-002542-f7l4ty2j 233 46 . . . cord-002542-f7l4ty2j 234 1 In in IN cord-002542-f7l4ty2j 234 2 the the DT cord-002542-f7l4ty2j 234 3 earliest early JJS cord-002542-f7l4ty2j 234 4 passages passage NNS cord-002542-f7l4ty2j 234 5 , , , cord-002542-f7l4ty2j 234 6 only~33 only~33 JJ cord-002542-f7l4ty2j 234 7 % % NN cord-002542-f7l4ty2j 234 8 of of IN cord-002542-f7l4ty2j 234 9 deletions deletion NNS cord-002542-f7l4ty2j 234 10 removed remove VBD cord-002542-f7l4ty2j 234 11 a a DT cord-002542-f7l4ty2j 234 12 multiple multiple NN cord-002542-f7l4ty2j 234 13 of of IN cord-002542-f7l4ty2j 234 14 3 3 CD cord-002542-f7l4ty2j 234 15 nucleotides nucleotide NNS cord-002542-f7l4ty2j 234 16 ( ( -LRB- cord-002542-f7l4ty2j 234 17 i.e. i.e. FW cord-002542-f7l4ty2j 234 18 they -PRON- PRP cord-002542-f7l4ty2j 234 19 thus thus RB cord-002542-f7l4ty2j 234 20 conserved conserve VBD cord-002542-f7l4ty2j 234 21 the the DT cord-002542-f7l4ty2j 234 22 ORF ORF NNP cord-002542-f7l4ty2j 234 23 ) ) -RRB- cord-002542-f7l4ty2j 234 24 , , , cord-002542-f7l4ty2j 234 25 as as IN cord-002542-f7l4ty2j 234 26 would would MD cord-002542-f7l4ty2j 234 27 be be VB cord-002542-f7l4ty2j 234 28 expected expect VBN cord-002542-f7l4ty2j 234 29 if if IN cord-002542-f7l4ty2j 234 30 deletion deletion NN cord-002542-f7l4ty2j 234 31 events event NNS cord-002542-f7l4ty2j 234 32 occurred occur VBD cord-002542-f7l4ty2j 234 33 randomly randomly RB cord-002542-f7l4ty2j 234 34 throughout throughout IN cord-002542-f7l4ty2j 234 35 the the DT cord-002542-f7l4ty2j 234 36 genome genome NN cord-002542-f7l4ty2j 234 37 . . . cord-002542-f7l4ty2j 235 1 However however RB cord-002542-f7l4ty2j 235 2 , , , cord-002542-f7l4ty2j 235 3 with with IN cord-002542-f7l4ty2j 235 4 continued continue VBN cord-002542-f7l4ty2j 235 5 passaging passaging NN cord-002542-f7l4ty2j 235 6 , , , cord-002542-f7l4ty2j 235 7 there there EX cord-002542-f7l4ty2j 235 8 was be VBD cord-002542-f7l4ty2j 235 9 a a DT cord-002542-f7l4ty2j 235 10 general general JJ cord-002542-f7l4ty2j 235 11 trend trend NN cord-002542-f7l4ty2j 235 12 toward toward IN cord-002542-f7l4ty2j 235 13 conservation conservation NN cord-002542-f7l4ty2j 235 14 of of IN cord-002542-f7l4ty2j 235 15 the the DT cord-002542-f7l4ty2j 235 16 ORF ORF NNP cord-002542-f7l4ty2j 235 17 for for IN cord-002542-f7l4ty2j 235 18 both both DT cord-002542-f7l4ty2j 235 19 RNA1 RNA1 NNP cord-002542-f7l4ty2j 235 20 and and CC cord-002542-f7l4ty2j 235 21 RNA2 RNA2 NNP cord-002542-f7l4ty2j 236 1 ( ( -LRB- cord-002542-f7l4ty2j 236 2 Fig Fig NNP cord-002542-f7l4ty2j 236 3 2D 2d NN cord-002542-f7l4ty2j 236 4 ) ) -RRB- cord-002542-f7l4ty2j 236 5 , , , cord-002542-f7l4ty2j 236 6 although although IN cord-002542-f7l4ty2j 236 7 this this DT cord-002542-f7l4ty2j 236 8 was be VBD cord-002542-f7l4ty2j 236 9 not not RB cord-002542-f7l4ty2j 236 10 the the DT cord-002542-f7l4ty2j 236 11 case case NN cord-002542-f7l4ty2j 236 12 for for IN cord-002542-f7l4ty2j 236 13 all all DT cord-002542-f7l4ty2j 236 14 replicates replicate NNS cord-002542-f7l4ty2j 236 15 . . . cord-002542-f7l4ty2j 237 1 Specifically specifically RB cord-002542-f7l4ty2j 237 2 , , , cord-002542-f7l4ty2j 237 3 while while IN cord-002542-f7l4ty2j 237 4 initially initially RB cord-002542-f7l4ty2j 237 5 showing show VBG cord-002542-f7l4ty2j 237 6 an an DT cord-002542-f7l4ty2j 237 7 increase increase NN cord-002542-f7l4ty2j 237 8 in in IN cord-002542-f7l4ty2j 237 9 ORF ORF NNP cord-002542-f7l4ty2j 237 10 conservation conservation NN cord-002542-f7l4ty2j 237 11 , , , cord-002542-f7l4ty2j 237 12 replicate replicate VB cord-002542-f7l4ty2j 237 13 2 2 CD cord-002542-f7l4ty2j 237 14 of of IN cord-002542-f7l4ty2j 237 15 RNA2 RNA2 NNP cord-002542-f7l4ty2j 237 16 showed show VBD cord-002542-f7l4ty2j 237 17 a a DT cord-002542-f7l4ty2j 237 18 decrease decrease NN cord-002542-f7l4ty2j 237 19 in in IN cord-002542-f7l4ty2j 237 20 the the DT cord-002542-f7l4ty2j 237 21 conservation conservation NN cord-002542-f7l4ty2j 237 22 of of IN cord-002542-f7l4ty2j 237 23 the the DT cord-002542-f7l4ty2j 237 24 ORF ORF NNP cord-002542-f7l4ty2j 237 25 after after IN cord-002542-f7l4ty2j 237 26 passage passage NN cord-002542-f7l4ty2j 237 27 4 4 CD cord-002542-f7l4ty2j 237 28 , , , cord-002542-f7l4ty2j 237 29 in in IN cord-002542-f7l4ty2j 237 30 contrast contrast NN cord-002542-f7l4ty2j 237 31 to to IN cord-002542-f7l4ty2j 237 32 the the DT cord-002542-f7l4ty2j 237 33 other other JJ cord-002542-f7l4ty2j 237 34 two two CD cord-002542-f7l4ty2j 237 35 replicates replicate NNS cord-002542-f7l4ty2j 237 36 , , , cord-002542-f7l4ty2j 237 37 and and CC cord-002542-f7l4ty2j 237 38 in in IN cord-002542-f7l4ty2j 237 39 fact fact NN cord-002542-f7l4ty2j 237 40 dips dip VBZ cord-002542-f7l4ty2j 237 41 below below IN cord-002542-f7l4ty2j 237 42 33 33 CD cord-002542-f7l4ty2j 237 43 % % NN cord-002542-f7l4ty2j 237 44 . . . cord-002542-f7l4ty2j 238 1 Closer close JJR cord-002542-f7l4ty2j 238 2 inspection inspection NN cord-002542-f7l4ty2j 238 3 of of IN cord-002542-f7l4ty2j 238 4 individual individual JJ cord-002542-f7l4ty2j 238 5 recombination recombination NN cord-002542-f7l4ty2j 238 6 events event NNS cord-002542-f7l4ty2j 238 7 shows show VBZ cord-002542-f7l4ty2j 238 8 that that IN cord-002542-f7l4ty2j 238 9 this this DT cord-002542-f7l4ty2j 238 10 trend trend NN cord-002542-f7l4ty2j 238 11 is be VBZ cord-002542-f7l4ty2j 238 12 driven drive VBN cord-002542-f7l4ty2j 238 13 by by IN cord-002542-f7l4ty2j 238 14 three three CD cord-002542-f7l4ty2j 238 15 of of IN cord-002542-f7l4ty2j 238 16 the the DT cord-002542-f7l4ty2j 238 17 four four CD cord-002542-f7l4ty2j 238 18 most most RBS cord-002542-f7l4ty2j 238 19 common common JJ cord-002542-f7l4ty2j 238 20 recombination recombination NN cord-002542-f7l4ty2j 238 21 events event NNS cord-002542-f7l4ty2j 238 22 in in IN cord-002542-f7l4ty2j 238 23 replicate replicate VBP cord-002542-f7l4ty2j 238 24 2 2 CD cord-002542-f7l4ty2j 238 25 passages passage NNS cord-002542-f7l4ty2j 238 26 4 4 CD cord-002542-f7l4ty2j 238 27 to to TO cord-002542-f7l4ty2j 238 28 9 9 CD cord-002542-f7l4ty2j 238 29 : : SYM cord-002542-f7l4ty2j 238 30 249 249 CD cord-002542-f7l4ty2j 238 31 ^ ^ SYM cord-002542-f7l4ty2j 238 32 517 517 CD cord-002542-f7l4ty2j 238 33 , , , cord-002542-f7l4ty2j 238 34 736 736 CD cord-002542-f7l4ty2j 238 35 ^ ^ SYM cord-002542-f7l4ty2j 238 36 1219 1219 CD cord-002542-f7l4ty2j 238 37 , , , cord-002542-f7l4ty2j 238 38 250 250 CD cord-002542-f7l4ty2j 238 39 ^ ^ SYM cord-002542-f7l4ty2j 238 40 513 513 CD cord-002542-f7l4ty2j 238 41 and and CC cord-002542-f7l4ty2j 239 1 249 249 CD cord-002542-f7l4ty2j 239 2 ^ ^ NFP cord-002542-f7l4ty2j 239 3 519 519 CD cord-002542-f7l4ty2j 239 4 ( ( -LRB- cord-002542-f7l4ty2j 239 5 the the DT cord-002542-f7l4ty2j 239 6 latter latter JJ cord-002542-f7l4ty2j 239 7 three three CD cord-002542-f7l4ty2j 239 8 events event NNS cord-002542-f7l4ty2j 239 9 in in IN cord-002542-f7l4ty2j 239 10 bold bold JJ cord-002542-f7l4ty2j 239 11 do do VBP cord-002542-f7l4ty2j 239 12 not not RB cord-002542-f7l4ty2j 239 13 maintain maintain VB cord-002542-f7l4ty2j 239 14 the the DT cord-002542-f7l4ty2j 239 15 ORF ORF NNP cord-002542-f7l4ty2j 239 16 ) ) -RRB- cord-002542-f7l4ty2j 239 17 . . . cord-002542-f7l4ty2j 240 1 These these DT cord-002542-f7l4ty2j 240 2 events event NNS cord-002542-f7l4ty2j 240 3 are be VBP cord-002542-f7l4ty2j 240 4 observed observe VBN cord-002542-f7l4ty2j 240 5 in in IN cord-002542-f7l4ty2j 240 6 the the DT cord-002542-f7l4ty2j 240 7 other other JJ cord-002542-f7l4ty2j 240 8 replicates replicate NNS cord-002542-f7l4ty2j 240 9 , , , cord-002542-f7l4ty2j 240 10 but but CC cord-002542-f7l4ty2j 240 11 at at IN cord-002542-f7l4ty2j 240 12 a a DT cord-002542-f7l4ty2j 240 13 much much RB cord-002542-f7l4ty2j 240 14 reduced reduce VBN cord-002542-f7l4ty2j 240 15 frequency frequency NN cord-002542-f7l4ty2j 240 16 ( ( -LRB- cord-002542-f7l4ty2j 240 17 no no DT cord-002542-f7l4ty2j 240 18 more more JJR cord-002542-f7l4ty2j 240 19 than than IN cord-002542-f7l4ty2j 240 20 1 1 CD cord-002542-f7l4ty2j 240 21 % % NN cord-002542-f7l4ty2j 240 22 of of IN cord-002542-f7l4ty2j 240 23 the the DT cord-002542-f7l4ty2j 240 24 total total JJ cord-002542-f7l4ty2j 240 25 RNA2 RNA2 NNP cord-002542-f7l4ty2j 240 26 recombination recombination NN cord-002542-f7l4ty2j 240 27 events event NNS cord-002542-f7l4ty2j 240 28 for for IN cord-002542-f7l4ty2j 240 29 reps rep NNS cord-002542-f7l4ty2j 240 30 1 1 CD cord-002542-f7l4ty2j 240 31 and and CC cord-002542-f7l4ty2j 240 32 3 3 CD cord-002542-f7l4ty2j 240 33 ) ) -RRB- cord-002542-f7l4ty2j 240 34 ( ( -LRB- cord-002542-f7l4ty2j 240 35 S1 S1 NNP cord-002542-f7l4ty2j 240 36 Datafile Datafile NNP cord-002542-f7l4ty2j 240 37 ) ) -RRB- cord-002542-f7l4ty2j 240 38 . . . cord-002542-f7l4ty2j 240 39 _SP cord-002542-f7l4ty2j 241 1 Using use VBG cord-002542-f7l4ty2j 241 2 ViReMa virema NN cord-002542-f7l4ty2j 241 3 , , , cord-002542-f7l4ty2j 241 4 we -PRON- PRP cord-002542-f7l4ty2j 241 5 were be VBD cord-002542-f7l4ty2j 241 6 able able JJ cord-002542-f7l4ty2j 241 7 to to TO cord-002542-f7l4ty2j 241 8 calculate calculate VB cord-002542-f7l4ty2j 241 9 the the DT cord-002542-f7l4ty2j 241 10 frequency frequency NN cord-002542-f7l4ty2j 241 11 with with IN cord-002542-f7l4ty2j 241 12 which which WDT cord-002542-f7l4ty2j 241 13 each each DT cord-002542-f7l4ty2j 241 14 nucleotide nucleotide NN cord-002542-f7l4ty2j 241 15 was be VBD cord-002542-f7l4ty2j 241 16 deleted delete VBN cord-002542-f7l4ty2j 241 17 , , , cord-002542-f7l4ty2j 241 18 revealing reveal VBG cord-002542-f7l4ty2j 241 19 areas area NNS cord-002542-f7l4ty2j 241 20 of of IN cord-002542-f7l4ty2j 241 21 the the DT cord-002542-f7l4ty2j 241 22 viral viral JJ cord-002542-f7l4ty2j 241 23 genome genome NN cord-002542-f7l4ty2j 241 24 that that WDT cord-002542-f7l4ty2j 241 25 are be VBP cord-002542-f7l4ty2j 241 26 conserved conserve VBN cord-002542-f7l4ty2j 241 27 during during IN cord-002542-f7l4ty2j 241 28 serial serial JJ cord-002542-f7l4ty2j 241 29 passaging passaging NN cord-002542-f7l4ty2j 241 30 and and CC cord-002542-f7l4ty2j 241 31 required require VBN cord-002542-f7l4ty2j 241 32 for for IN cord-002542-f7l4ty2j 241 33 DI DI NNP cord-002542-f7l4ty2j 241 34 - - HYPH cord-002542-f7l4ty2j 241 35 RNA RNA NNP cord-002542-f7l4ty2j 241 36 replication replication NN cord-002542-f7l4ty2j 241 37 . . . cord-002542-f7l4ty2j 242 1 We -PRON- PRP cord-002542-f7l4ty2j 242 2 plotted plot VBD cord-002542-f7l4ty2j 242 3 these these DT cord-002542-f7l4ty2j 242 4 data datum NNS cord-002542-f7l4ty2j 242 5 to to TO cord-002542-f7l4ty2j 242 6 generate generate VB cord-002542-f7l4ty2j 242 7 recombination recombination NN cord-002542-f7l4ty2j 242 8 profiling profiling NN cord-002542-f7l4ty2j 242 9 maps map NNS cord-002542-f7l4ty2j 242 10 for for IN cord-002542-f7l4ty2j 242 11 each each DT cord-002542-f7l4ty2j 242 12 RNA RNA NNP cord-002542-f7l4ty2j 242 13 of of IN cord-002542-f7l4ty2j 242 14 FHV FHV NNP cord-002542-f7l4ty2j 242 15 throughout throughout IN cord-002542-f7l4ty2j 242 16 passaging passage VBG cord-002542-f7l4ty2j 242 17 ( ( -LRB- cord-002542-f7l4ty2j 242 18 Fig Fig NNP cord-002542-f7l4ty2j 242 19 3 3 CD cord-002542-f7l4ty2j 242 20 and and CC cord-002542-f7l4ty2j 242 21 S2 S2 NNP cord-002542-f7l4ty2j 242 22 Fig Fig NNP cord-002542-f7l4ty2j 242 23 ) ) -RRB- cord-002542-f7l4ty2j 242 24 . . . cord-002542-f7l4ty2j 243 1 In in IN cord-002542-f7l4ty2j 243 2 the the DT cord-002542-f7l4ty2j 243 3 first first JJ cord-002542-f7l4ty2j 243 4 passage passage NN cord-002542-f7l4ty2j 243 5 , , , cord-002542-f7l4ty2j 243 6 there there EX cord-002542-f7l4ty2j 243 7 is be VBZ cord-002542-f7l4ty2j 243 8 a a DT cord-002542-f7l4ty2j 243 9 relatively relatively RB cord-002542-f7l4ty2j 243 10 even even JJ cord-002542-f7l4ty2j 243 11 distribution distribution NN cord-002542-f7l4ty2j 243 12 of of IN cord-002542-f7l4ty2j 243 13 nucleotide nucleotide JJ cord-002542-f7l4ty2j 243 14 deletions deletion NNS cord-002542-f7l4ty2j 243 15 along along IN cord-002542-f7l4ty2j 243 16 the the DT cord-002542-f7l4ty2j 243 17 whole whole JJ cord-002542-f7l4ty2j 243 18 length length NN cord-002542-f7l4ty2j 243 19 of of IN cord-002542-f7l4ty2j 243 20 the the DT cord-002542-f7l4ty2j 243 21 genome genome NN cord-002542-f7l4ty2j 243 22 with with IN cord-002542-f7l4ty2j 243 23 the the DT cord-002542-f7l4ty2j 243 24 exception exception NN cord-002542-f7l4ty2j 243 25 of of IN cord-002542-f7l4ty2j 243 26 two two CD cord-002542-f7l4ty2j 243 27 frequently frequently RB cord-002542-f7l4ty2j 243 28 excised excise VBN cord-002542-f7l4ty2j 243 29 regions region NNS cord-002542-f7l4ty2j 243 30 in in IN cord-002542-f7l4ty2j 243 31 the the DT cord-002542-f7l4ty2j 243 32 3 3 CD cord-002542-f7l4ty2j 243 33 ' ' NN cord-002542-f7l4ty2j 243 34 end end NN cord-002542-f7l4ty2j 243 35 in in IN cord-002542-f7l4ty2j 243 36 RNA1 RNA1 NNP cord-002542-f7l4ty2j 243 37 due due IN cord-002542-f7l4ty2j 243 38 to to IN cord-002542-f7l4ty2j 243 39 two two CD cord-002542-f7l4ty2j 243 40 common common JJ cord-002542-f7l4ty2j 243 41 recombination recombination NN cord-002542-f7l4ty2j 243 42 events event NNS cord-002542-f7l4ty2j 243 43 in in IN cord-002542-f7l4ty2j 243 44 each each DT cord-002542-f7l4ty2j 243 45 of of IN cord-002542-f7l4ty2j 243 46 the the DT cord-002542-f7l4ty2j 243 47 replicates replicate NNS cord-002542-f7l4ty2j 243 48 : : : cord-002542-f7l4ty2j 243 49 2545 2545 CD cord-002542-f7l4ty2j 243 50 ^ ^ NFP cord-002542-f7l4ty2j 243 51 2685 2685 CD cord-002542-f7l4ty2j 243 52 and and CC cord-002542-f7l4ty2j 243 53 2277 2277 CD cord-002542-f7l4ty2j 243 54 ^ ^ NFP cord-002542-f7l4ty2j 243 55 2435 2435 CD cord-002542-f7l4ty2j 243 56 . . . cord-002542-f7l4ty2j 244 1 By by IN cord-002542-f7l4ty2j 244 2 passage passage NN cord-002542-f7l4ty2j 244 3 3 3 CD cord-002542-f7l4ty2j 244 4 the the DT cord-002542-f7l4ty2j 244 5 deletions deletion NNS cord-002542-f7l4ty2j 244 6 along along IN cord-002542-f7l4ty2j 244 7 the the DT cord-002542-f7l4ty2j 244 8 genomic genomic JJ cord-002542-f7l4ty2j 244 9 landscape landscape NN cord-002542-f7l4ty2j 244 10 begin begin VBP cord-002542-f7l4ty2j 244 11 to to TO cord-002542-f7l4ty2j 244 12 be be VB cord-002542-f7l4ty2j 244 13 ' ' `` cord-002542-f7l4ty2j 244 14 sculpted sculpt VBN cord-002542-f7l4ty2j 244 15 ' ' '' cord-002542-f7l4ty2j 244 16 whereby whereby WRB cord-002542-f7l4ty2j 244 17 certain certain JJ cord-002542-f7l4ty2j 244 18 regions region NNS cord-002542-f7l4ty2j 244 19 are be VBP cord-002542-f7l4ty2j 244 20 deleted delete VBN cord-002542-f7l4ty2j 244 21 with with IN cord-002542-f7l4ty2j 244 22 a a DT cord-002542-f7l4ty2j 244 23 greater great JJR cord-002542-f7l4ty2j 244 24 frequency frequency NN cord-002542-f7l4ty2j 244 25 than than IN cord-002542-f7l4ty2j 244 26 others other NNS cord-002542-f7l4ty2j 244 27 . . . cord-002542-f7l4ty2j 245 1 Passages passage NNS cord-002542-f7l4ty2j 245 2 5 5 CD cord-002542-f7l4ty2j 245 3 , , , cord-002542-f7l4ty2j 245 4 7 7 CD cord-002542-f7l4ty2j 245 5 , , , cord-002542-f7l4ty2j 245 6 and and CC cord-002542-f7l4ty2j 245 7 9 9 CD cord-002542-f7l4ty2j 245 8 were be VBD cord-002542-f7l4ty2j 245 9 sculpted sculpt VBN cord-002542-f7l4ty2j 245 10 further further RB cord-002542-f7l4ty2j 245 11 revealing reveal VBG cord-002542-f7l4ty2j 245 12 three three CD cord-002542-f7l4ty2j 245 13 major major JJ cord-002542-f7l4ty2j 245 14 regions region NNS cord-002542-f7l4ty2j 245 15 that that WDT cord-002542-f7l4ty2j 245 16 were be VBD cord-002542-f7l4ty2j 245 17 deleted delete VBN cord-002542-f7l4ty2j 245 18 in in IN cord-002542-f7l4ty2j 245 19 RNA1 RNA1 NNP cord-002542-f7l4ty2j 245 20 and and CC cord-002542-f7l4ty2j 245 21 two two CD cord-002542-f7l4ty2j 245 22 in in IN cord-002542-f7l4ty2j 245 23 RNA2 RNA2 NNP cord-002542-f7l4ty2j 245 24 . . . cord-002542-f7l4ty2j 246 1 Interestingly interestingly RB cord-002542-f7l4ty2j 246 2 , , , cord-002542-f7l4ty2j 246 3 for for IN cord-002542-f7l4ty2j 246 4 both both DT cord-002542-f7l4ty2j 246 5 RNA RNA NNP cord-002542-f7l4ty2j 246 6 segments segment NNS cord-002542-f7l4ty2j 246 7 , , , cord-002542-f7l4ty2j 246 8 while while IN cord-002542-f7l4ty2j 246 9 a a DT cord-002542-f7l4ty2j 246 10 range range NN cord-002542-f7l4ty2j 246 11 of of IN cord-002542-f7l4ty2j 246 12 deletions deletion NNS cord-002542-f7l4ty2j 246 13 and and CC cord-002542-f7l4ty2j 246 14 rearrangements rearrangement NNS cord-002542-f7l4ty2j 246 15 are be VBP cord-002542-f7l4ty2j 246 16 generated generate VBN cord-002542-f7l4ty2j 246 17 during during IN cord-002542-f7l4ty2j 246 18 early early JJ cord-002542-f7l4ty2j 246 19 passages passage NNS cord-002542-f7l4ty2j 246 20 , , , cord-002542-f7l4ty2j 246 21 only only RB cord-002542-f7l4ty2j 246 22 the the DT cord-002542-f7l4ty2j 246 23 deletions deletion NNS cord-002542-f7l4ty2j 246 24 that that WDT cord-002542-f7l4ty2j 246 25 maintain maintain VBP cord-002542-f7l4ty2j 246 26 regulatory regulatory JJ cord-002542-f7l4ty2j 246 27 and and CC cord-002542-f7l4ty2j 246 28 control control NN cord-002542-f7l4ty2j 246 29 elements element NNS cord-002542-f7l4ty2j 246 30 are be VBP cord-002542-f7l4ty2j 246 31 amplified amplify VBN cord-002542-f7l4ty2j 246 32 during during IN cord-002542-f7l4ty2j 246 33 continued continued JJ cord-002542-f7l4ty2j 246 34 passaging passaging NN cord-002542-f7l4ty2j 246 35 , , , cord-002542-f7l4ty2j 246 36 as as IN cord-002542-f7l4ty2j 246 37 previously previously RB cord-002542-f7l4ty2j 246 38 observed observe VBN cord-002542-f7l4ty2j 246 39 in in IN cord-002542-f7l4ty2j 246 40 FHV FHV NNP cord-002542-f7l4ty2j 246 41 [ [ -LRB- cord-002542-f7l4ty2j 246 42 32 32 CD cord-002542-f7l4ty2j 246 43 ] ] -RRB- cord-002542-f7l4ty2j 246 44 . . . cord-002542-f7l4ty2j 247 1 These these DT cord-002542-f7l4ty2j 247 2 include include VBP cord-002542-f7l4ty2j 247 3 the the DT cord-002542-f7l4ty2j 247 4 5'/3 5'/3 CD cord-002542-f7l4ty2j 247 5 ' ' POS cord-002542-f7l4ty2j 247 6 UTRs utr NNS cord-002542-f7l4ty2j 247 7 and and CC cord-002542-f7l4ty2j 247 8 internal internal JJ cord-002542-f7l4ty2j 247 9 response response NN cord-002542-f7l4ty2j 247 10 elements element NNS cord-002542-f7l4ty2j 247 11 ( ( -LRB- cord-002542-f7l4ty2j 247 12 intRE intRE NNP cord-002542-f7l4ty2j 247 13 ) ) -RRB- cord-002542-f7l4ty2j 247 14 of of IN cord-002542-f7l4ty2j 247 15 both both DT cord-002542-f7l4ty2j 247 16 genomes genome NNS cord-002542-f7l4ty2j 247 17 , , , cord-002542-f7l4ty2j 247 18 as as RB cord-002542-f7l4ty2j 247 19 well well RB cord-002542-f7l4ty2j 247 20 as as IN cord-002542-f7l4ty2j 247 21 the the DT cord-002542-f7l4ty2j 247 22 Proximal Proximal NNP cord-002542-f7l4ty2j 247 23 - - : cord-002542-f7l4ty2j 247 24 and and CC cord-002542-f7l4ty2j 247 25 Distal Distal NNP cord-002542-f7l4ty2j 247 26 - - HYPH cord-002542-f7l4ty2j 247 27 Subgenomic Subgenomic NNP cord-002542-f7l4ty2j 247 28 Control Control NNP cord-002542-f7l4ty2j 247 29 Elements Elements NNP cord-002542-f7l4ty2j 247 30 ( ( -LRB- cord-002542-f7l4ty2j 247 31 PSCE PSCE NNP cord-002542-f7l4ty2j 247 32 and and CC cord-002542-f7l4ty2j 247 33 DSCE DSCE NNP cord-002542-f7l4ty2j 247 34 ) ) -RRB- cord-002542-f7l4ty2j 247 35 in in IN cord-002542-f7l4ty2j 247 36 RNA1 RNA1 NNP cord-002542-f7l4ty2j 247 37 ( ( -LRB- cord-002542-f7l4ty2j 247 38 Fig Fig NNP cord-002542-f7l4ty2j 247 39 3 3 CD cord-002542-f7l4ty2j 247 40 ) ) -RRB- cord-002542-f7l4ty2j 247 41 , , , cord-002542-f7l4ty2j 247 42 which which WDT cord-002542-f7l4ty2j 247 43 correlates correlate VBZ cord-002542-f7l4ty2j 247 44 to to IN cord-002542-f7l4ty2j 247 45 the the DT cord-002542-f7l4ty2j 247 46 findings finding NNS cord-002542-f7l4ty2j 247 47 that that IN cord-002542-f7l4ty2j 247 48 these these DT cord-002542-f7l4ty2j 247 49 regions region NNS cord-002542-f7l4ty2j 247 50 are be VBP cord-002542-f7l4ty2j 247 51 important important JJ cord-002542-f7l4ty2j 247 52 and and CC cord-002542-f7l4ty2j 247 53 required require VBN cord-002542-f7l4ty2j 247 54 for for IN cord-002542-f7l4ty2j 247 55 RNA RNA NNP cord-002542-f7l4ty2j 247 56 replication replication NN cord-002542-f7l4ty2j 247 57 and and CC cord-002542-f7l4ty2j 247 58 encapsidation encapsidation NN cord-002542-f7l4ty2j 247 59 [ [ -LRB- cord-002542-f7l4ty2j 247 60 29 29 CD cord-002542-f7l4ty2j 247 61 , , , cord-002542-f7l4ty2j 247 62 30 30 CD cord-002542-f7l4ty2j 247 63 , , , cord-002542-f7l4ty2j 247 64 32 32 CD cord-002542-f7l4ty2j 247 65 , , , cord-002542-f7l4ty2j 247 66 [ [ -LRB- cord-002542-f7l4ty2j 247 67 60 60 CD cord-002542-f7l4ty2j 247 68 ] ] -RRB- cord-002542-f7l4ty2j 247 69 [ [ -LRB- cord-002542-f7l4ty2j 247 70 61 61 CD cord-002542-f7l4ty2j 247 71 ] ] -RRB- cord-002542-f7l4ty2j 247 72 [ [ -LRB- cord-002542-f7l4ty2j 247 73 62 62 CD cord-002542-f7l4ty2j 247 74 ] ] -RRB- cord-002542-f7l4ty2j 247 75 [ [ -LRB- cord-002542-f7l4ty2j 247 76 63 63 CD cord-002542-f7l4ty2j 247 77 ] ] -RRB- cord-002542-f7l4ty2j 247 78 [ [ -LRB- cord-002542-f7l4ty2j 247 79 64 64 CD cord-002542-f7l4ty2j 247 80 ] ] -RRB- cord-002542-f7l4ty2j 247 81 . . . cord-002542-f7l4ty2j 248 1 The the DT cord-002542-f7l4ty2j 248 2 short short RB cord-002542-f7l4ty2j 248 3 - - HYPH cord-002542-f7l4ty2j 248 4 read read VBN cord-002542-f7l4ty2j 248 5 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 248 6 data datum NNS cord-002542-f7l4ty2j 248 7 provide provide VBP cord-002542-f7l4ty2j 248 8 in in IN cord-002542-f7l4ty2j 248 9 - - HYPH cord-002542-f7l4ty2j 248 10 depth depth NN cord-002542-f7l4ty2j 248 11 and and CC cord-002542-f7l4ty2j 248 12 high high JJ cord-002542-f7l4ty2j 248 13 resolution resolution NN cord-002542-f7l4ty2j 248 14 details detail NNS cord-002542-f7l4ty2j 248 15 of of IN cord-002542-f7l4ty2j 248 16 individual individual JJ cord-002542-f7l4ty2j 248 17 recombination recombination NN cord-002542-f7l4ty2j 248 18 events event NNS cord-002542-f7l4ty2j 248 19 . . . cord-002542-f7l4ty2j 249 1 However however RB cord-002542-f7l4ty2j 249 2 , , , cord-002542-f7l4ty2j 249 3 in in IN cord-002542-f7l4ty2j 249 4 order order NN cord-002542-f7l4ty2j 249 5 to to TO cord-002542-f7l4ty2j 249 6 determine determine VB cord-002542-f7l4ty2j 249 7 the the DT cord-002542-f7l4ty2j 249 8 correlation correlation NN cord-002542-f7l4ty2j 249 9 of of IN cord-002542-f7l4ty2j 249 10 these these DT cord-002542-f7l4ty2j 249 11 events event NNS cord-002542-f7l4ty2j 249 12 over over IN cord-002542-f7l4ty2j 249 13 time time NN cord-002542-f7l4ty2j 249 14 , , , cord-002542-f7l4ty2j 249 15 we -PRON- PRP cord-002542-f7l4ty2j 249 16 used use VBD cord-002542-f7l4ty2j 249 17 long long RB cord-002542-f7l4ty2j 249 18 - - HYPH cord-002542-f7l4ty2j 249 19 read read VBN cord-002542-f7l4ty2j 249 20 ONT ONT NNP cord-002542-f7l4ty2j 249 21 nanopore nanopore NNP cord-002542-f7l4ty2j 249 22 sequencing sequencing NN cord-002542-f7l4ty2j 249 23 , , , cord-002542-f7l4ty2j 249 24 which which WDT cord-002542-f7l4ty2j 249 25 can can MD cord-002542-f7l4ty2j 249 26 characterize characterize VB cord-002542-f7l4ty2j 249 27 full full JJ cord-002542-f7l4ty2j 249 28 - - HYPH cord-002542-f7l4ty2j 249 29 length length NN cord-002542-f7l4ty2j 249 30 wildtype wildtype NN cord-002542-f7l4ty2j 249 31 and and CC cord-002542-f7l4ty2j 249 32 defective defective JJ cord-002542-f7l4ty2j 249 33 genomes genome NNS cord-002542-f7l4ty2j 249 34 ( ( -LRB- cord-002542-f7l4ty2j 249 35 Fig Fig NNP cord-002542-f7l4ty2j 249 36 4 4 CD cord-002542-f7l4ty2j 249 37 and and CC cord-002542-f7l4ty2j 249 38 S4 S4 NNP cord-002542-f7l4ty2j 249 39 Fig Fig NNP cord-002542-f7l4ty2j 249 40 ) ) -RRB- cord-002542-f7l4ty2j 249 41 . . . cord-002542-f7l4ty2j 250 1 We -PRON- PRP cord-002542-f7l4ty2j 250 2 reverse reverse VBP cord-002542-f7l4ty2j 250 3 transcribed transcribe VBN cord-002542-f7l4ty2j 250 4 and and CC cord-002542-f7l4ty2j 250 5 amplified amplify VBN cord-002542-f7l4ty2j 250 6 both both DT cord-002542-f7l4ty2j 250 7 RNA RNA NNP cord-002542-f7l4ty2j 250 8 genes gene NNS cord-002542-f7l4ty2j 250 9 using use VBG cord-002542-f7l4ty2j 250 10 primers primer NNS cord-002542-f7l4ty2j 250 11 specific specific JJ cord-002542-f7l4ty2j 250 12 to to IN cord-002542-f7l4ty2j 250 13 the the DT cord-002542-f7l4ty2j 250 14 5 5 CD cord-002542-f7l4ty2j 250 15 ' ' '' cord-002542-f7l4ty2j 250 16 and and CC cord-002542-f7l4ty2j 250 17 3 3 CD cord-002542-f7l4ty2j 250 18 ' ' POS cord-002542-f7l4ty2j 250 19 UTRs utr NNS cord-002542-f7l4ty2j 250 20 of of IN cord-002542-f7l4ty2j 250 21 RNA1 RNA1 NNP cord-002542-f7l4ty2j 250 22 and and CC cord-002542-f7l4ty2j 250 23 RNA2 RNA2 NNP cord-002542-f7l4ty2j 250 24 from from IN cord-002542-f7l4ty2j 250 25 all all DT cord-002542-f7l4ty2j 250 26 passages passage NNS cord-002542-f7l4ty2j 250 27 of of IN cord-002542-f7l4ty2j 250 28 replicate replicate VB cord-002542-f7l4ty2j 250 29 2 2 CD cord-002542-f7l4ty2j 250 30 to to TO cord-002542-f7l4ty2j 250 31 obtain obtain VB cord-002542-f7l4ty2j 250 32 cDNA cdna NN cord-002542-f7l4ty2j 250 33 that that WDT cord-002542-f7l4ty2j 250 34 could could MD cord-002542-f7l4ty2j 250 35 be be VB cord-002542-f7l4ty2j 250 36 barcoded barcode VBN cord-002542-f7l4ty2j 250 37 and and CC cord-002542-f7l4ty2j 250 38 analyzed analyze VBN cord-002542-f7l4ty2j 250 39 using use VBG cord-002542-f7l4ty2j 250 40 protocols protocol NNS cord-002542-f7l4ty2j 250 41 for for IN cord-002542-f7l4ty2j 250 42 2D 2d NN cord-002542-f7l4ty2j 250 43 sequencing sequencing NN cord-002542-f7l4ty2j 250 44 on on IN cord-002542-f7l4ty2j 250 45 the the DT cord-002542-f7l4ty2j 250 46 ONT ONT NNP cord-002542-f7l4ty2j 250 47 MinION minion NN cord-002542-f7l4ty2j 250 48 . . . cord-002542-f7l4ty2j 251 1 The the DT cord-002542-f7l4ty2j 251 2 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 251 3 data datum NNS cord-002542-f7l4ty2j 251 4 shows show VBZ cord-002542-f7l4ty2j 251 5 that that IN cord-002542-f7l4ty2j 251 6 these these DT cord-002542-f7l4ty2j 251 7 regions region NNS cord-002542-f7l4ty2j 251 8 were be VBD cord-002542-f7l4ty2j 251 9 highly highly RB cord-002542-f7l4ty2j 251 10 conserved conserve VBN cord-002542-f7l4ty2j 251 11 during during IN cord-002542-f7l4ty2j 251 12 passaging passage VBG cord-002542-f7l4ty2j 251 13 ( ( -LRB- cord-002542-f7l4ty2j 251 14 Fig Fig NNP cord-002542-f7l4ty2j 251 15 3 3 CD cord-002542-f7l4ty2j 251 16 ) ) -RRB- cord-002542-f7l4ty2j 251 17 , , , cord-002542-f7l4ty2j 251 18 therefore therefore RB cord-002542-f7l4ty2j 251 19 we -PRON- PRP cord-002542-f7l4ty2j 251 20 were be VBD cord-002542-f7l4ty2j 251 21 confident confident JJ cord-002542-f7l4ty2j 251 22 using use VBG cord-002542-f7l4ty2j 251 23 template template NN cord-002542-f7l4ty2j 251 24 - - HYPH cord-002542-f7l4ty2j 251 25 specific specific JJ cord-002542-f7l4ty2j 251 26 primers primer NNS cord-002542-f7l4ty2j 251 27 to to IN cord-002542-f7l4ty2j 251 28 these these DT cord-002542-f7l4ty2j 251 29 regions region NNS cord-002542-f7l4ty2j 251 30 would would MD cord-002542-f7l4ty2j 251 31 capture capture VB cord-002542-f7l4ty2j 251 32 both both CC cord-002542-f7l4ty2j 251 33 the the DT cord-002542-f7l4ty2j 251 34 full full JJ cord-002542-f7l4ty2j 251 35 - - HYPH cord-002542-f7l4ty2j 251 36 length length NN cord-002542-f7l4ty2j 251 37 wild wild JJ cord-002542-f7l4ty2j 251 38 - - HYPH cord-002542-f7l4ty2j 251 39 type type NN cord-002542-f7l4ty2j 251 40 virus virus NN cord-002542-f7l4ty2j 251 41 genomes genome NNS cord-002542-f7l4ty2j 251 42 as as RB cord-002542-f7l4ty2j 251 43 well well RB cord-002542-f7l4ty2j 251 44 as as IN cord-002542-f7l4ty2j 251 45 any any DT cord-002542-f7l4ty2j 251 46 defective defective JJ cord-002542-f7l4ty2j 251 47 RNAs rna NNS cord-002542-f7l4ty2j 251 48 . . . cord-002542-f7l4ty2j 252 1 After after IN cord-002542-f7l4ty2j 252 2 PCR PCR NNP cord-002542-f7l4ty2j 252 3 amplification amplification NN cord-002542-f7l4ty2j 252 4 , , , cord-002542-f7l4ty2j 252 5 we -PRON- PRP cord-002542-f7l4ty2j 252 6 analyzed analyze VBD cord-002542-f7l4ty2j 252 7 the the DT cord-002542-f7l4ty2j 252 8 MinION minion FW cord-002542-f7l4ty2j 252 9 cDNA cdna NN cord-002542-f7l4ty2j 252 10 libraries library NNS cord-002542-f7l4ty2j 252 11 using use VBG cord-002542-f7l4ty2j 252 12 agarose agarose VBN cord-002542-f7l4ty2j 252 13 gel gel NN cord-002542-f7l4ty2j 252 14 electrophoresis electrophoresis NN cord-002542-f7l4ty2j 252 15 to to TO cord-002542-f7l4ty2j 252 16 observe observe VB cord-002542-f7l4ty2j 252 17 the the DT cord-002542-f7l4ty2j 252 18 distribution distribution NN cord-002542-f7l4ty2j 252 19 of of IN cord-002542-f7l4ty2j 252 20 cDNA cdna NN cord-002542-f7l4ty2j 252 21 fragments fragment NNS cord-002542-f7l4ty2j 252 22 and and CC cord-002542-f7l4ty2j 252 23 ratios ratio NNS cord-002542-f7l4ty2j 252 24 of of IN cord-002542-f7l4ty2j 252 25 full full JJ cord-002542-f7l4ty2j 252 26 - - HYPH cord-002542-f7l4ty2j 252 27 length length NN cord-002542-f7l4ty2j 252 28 to to IN cord-002542-f7l4ty2j 252 29 defective defective JJ cord-002542-f7l4ty2j 252 30 RNA RNA NNP cord-002542-f7l4ty2j 252 31 genomes genome NNS cord-002542-f7l4ty2j 252 32 ( ( -LRB- cord-002542-f7l4ty2j 252 33 Fig Fig NNP cord-002542-f7l4ty2j 252 34 5A 5a NN cord-002542-f7l4ty2j 252 35 ) ) -RRB- cord-002542-f7l4ty2j 252 36 . . . cord-002542-f7l4ty2j 253 1 While while IN cord-002542-f7l4ty2j 253 2 the the DT cord-002542-f7l4ty2j 253 3 cDNAs cdna NNS cord-002542-f7l4ty2j 253 4 from from IN cord-002542-f7l4ty2j 253 5 the the DT cord-002542-f7l4ty2j 253 6 early early JJ cord-002542-f7l4ty2j 253 7 passages passage NNS cord-002542-f7l4ty2j 253 8 are be VBP cord-002542-f7l4ty2j 253 9 predominantly predominantly RB cord-002542-f7l4ty2j 253 10 of of IN cord-002542-f7l4ty2j 253 11 the the DT cord-002542-f7l4ty2j 253 12 expected expect VBN cord-002542-f7l4ty2j 253 13 size size NN cord-002542-f7l4ty2j 253 14 for for IN cord-002542-f7l4ty2j 253 15 full full JJ cord-002542-f7l4ty2j 253 16 - - HYPH cord-002542-f7l4ty2j 253 17 length length NN cord-002542-f7l4ty2j 253 18 RNA RNA NNP cord-002542-f7l4ty2j 253 19 genomes genome NNS cord-002542-f7l4ty2j 253 20 , , , cord-002542-f7l4ty2j 253 21 later later RB cord-002542-f7l4ty2j 253 22 passages passage NNS cord-002542-f7l4ty2j 253 23 contain contain VBP cord-002542-f7l4ty2j 253 24 an an DT cord-002542-f7l4ty2j 253 25 array array NN cord-002542-f7l4ty2j 253 26 of of IN cord-002542-f7l4ty2j 253 27 band band NN cord-002542-f7l4ty2j 253 28 sizes size NNS cord-002542-f7l4ty2j 253 29 . . . cord-002542-f7l4ty2j 254 1 This this DT cord-002542-f7l4ty2j 254 2 shows show VBZ cord-002542-f7l4ty2j 254 3 that that IN cord-002542-f7l4ty2j 254 4 in in IN cord-002542-f7l4ty2j 254 5 the the DT cord-002542-f7l4ty2j 254 6 early early JJ cord-002542-f7l4ty2j 254 7 passages passage NNS cord-002542-f7l4ty2j 254 8 the the DT cord-002542-f7l4ty2j 254 9 full full JJ cord-002542-f7l4ty2j 254 10 - - HYPH cord-002542-f7l4ty2j 254 11 length length NN cord-002542-f7l4ty2j 254 12 genome genome NN cord-002542-f7l4ty2j 254 13 is be VBZ cord-002542-f7l4ty2j 254 14 the the DT cord-002542-f7l4ty2j 254 15 predominant predominant JJ cord-002542-f7l4ty2j 254 16 species specie NNS cord-002542-f7l4ty2j 254 17 while while IN cord-002542-f7l4ty2j 254 18 in in IN cord-002542-f7l4ty2j 254 19 later later JJ cord-002542-f7l4ty2j 254 20 passages passage VBZ cord-002542-f7l4ty2j 254 21 the the DT cord-002542-f7l4ty2j 254 22 truncated truncated JJ cord-002542-f7l4ty2j 254 23 version version NN cord-002542-f7l4ty2j 254 24 becomes become VBZ cord-002542-f7l4ty2j 254 25 predominant predominant JJ cord-002542-f7l4ty2j 254 26 . . . cord-002542-f7l4ty2j 255 1 We -PRON- PRP cord-002542-f7l4ty2j 255 2 also also RB cord-002542-f7l4ty2j 255 3 observe observe VBP cord-002542-f7l4ty2j 255 4 species specie NNS cord-002542-f7l4ty2j 255 5 appearing appear VBG cord-002542-f7l4ty2j 255 6 to to TO cord-002542-f7l4ty2j 255 7 be be VB cord-002542-f7l4ty2j 255 8 larger large JJR cord-002542-f7l4ty2j 255 9 than than IN cord-002542-f7l4ty2j 255 10 RNA2 RNA2 NNP cord-002542-f7l4ty2j 255 11 . . . cord-002542-f7l4ty2j 256 1 It -PRON- PRP cord-002542-f7l4ty2j 256 2 is be VBZ cord-002542-f7l4ty2j 256 3 possible possible JJ cord-002542-f7l4ty2j 256 4 that that IN cord-002542-f7l4ty2j 256 5 some some DT cord-002542-f7l4ty2j 256 6 of of IN cord-002542-f7l4ty2j 256 7 these these DT cord-002542-f7l4ty2j 256 8 species specie NNS cord-002542-f7l4ty2j 256 9 correspond correspond VBP cord-002542-f7l4ty2j 256 10 to to IN cord-002542-f7l4ty2j 256 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 256 12 homodimers homodimer NNS cord-002542-f7l4ty2j 256 13 or or CC cord-002542-f7l4ty2j 256 14 other other JJ cord-002542-f7l4ty2j 256 15 complex complex JJ cord-002542-f7l4ty2j 256 16 rearrangements rearrangement NNS cord-002542-f7l4ty2j 256 17 that that WDT cord-002542-f7l4ty2j 256 18 have have VBP cord-002542-f7l4ty2j 256 19 previously previously RB cord-002542-f7l4ty2j 256 20 been be VBN cord-002542-f7l4ty2j 256 21 observed observe VBN cord-002542-f7l4ty2j 256 22 [ [ -LRB- cord-002542-f7l4ty2j 256 23 65 65 CD cord-002542-f7l4ty2j 256 24 ] ] -RRB- cord-002542-f7l4ty2j 256 25 and and CC cord-002542-f7l4ty2j 256 26 would would MD cord-002542-f7l4ty2j 256 27 result result VB cord-002542-f7l4ty2j 256 28 in in IN cord-002542-f7l4ty2j 256 29 an an DT cord-002542-f7l4ty2j 256 30 increased increase VBN cord-002542-f7l4ty2j 256 31 molecular molecular JJ cord-002542-f7l4ty2j 256 32 weight weight NN cord-002542-f7l4ty2j 256 33 . . . cord-002542-f7l4ty2j 257 1 Evidence evidence NN cord-002542-f7l4ty2j 257 2 of of IN cord-002542-f7l4ty2j 257 3 RNA1 RNA1 NNP cord-002542-f7l4ty2j 257 4 homodimers homodimer NNS cord-002542-f7l4ty2j 257 5 ( ( -LRB- cord-002542-f7l4ty2j 257 6 3107 3107 CD cord-002542-f7l4ty2j 257 7 ^ ^ SYM cord-002542-f7l4ty2j 257 8 1 1 CD cord-002542-f7l4ty2j 257 9 ) ) -RRB- cord-002542-f7l4ty2j 257 10 , , , cord-002542-f7l4ty2j 257 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 257 12 homodimers homodimer NNS cord-002542-f7l4ty2j 257 13 ( ( -LRB- cord-002542-f7l4ty2j 257 14 1400 1400 CD cord-002542-f7l4ty2j 257 15 ^ ^ SYM cord-002542-f7l4ty2j 257 16 1 1 CD cord-002542-f7l4ty2j 257 17 ) ) -RRB- cord-002542-f7l4ty2j 257 18 , , , cord-002542-f7l4ty2j 257 19 and and CC cord-002542-f7l4ty2j 257 20 RNA2 RNA2 NNP cord-002542-f7l4ty2j 257 21 to to IN cord-002542-f7l4ty2j 257 22 RNA3 RNA3 NNP cord-002542-f7l4ty2j 257 23 heterodimers heterodimer NNS cord-002542-f7l4ty2j 257 24 ( ( -LRB- cord-002542-f7l4ty2j 257 25 1400 1400 CD cord-002542-f7l4ty2j 257 26 ^ ^ SYM cord-002542-f7l4ty2j 257 27 2720 2720 CD cord-002542-f7l4ty2j 257 28 ) ) -RRB- cord-002542-f7l4ty2j 257 29 can can MD cord-002542-f7l4ty2j 257 30 also also RB cord-002542-f7l4ty2j 257 31 be be VB cord-002542-f7l4ty2j 257 32 found find VBN cord-002542-f7l4ty2j 257 33 in in IN cord-002542-f7l4ty2j 257 34 the the DT cord-002542-f7l4ty2j 257 35 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 257 36 data datum NNS cord-002542-f7l4ty2j 257 37 ( ( -LRB- cord-002542-f7l4ty2j 257 38 S1 S1 NNP cord-002542-f7l4ty2j 257 39 Datafile Datafile NNP cord-002542-f7l4ty2j 257 40 ) ) -RRB- cord-002542-f7l4ty2j 257 41 . . . cord-002542-f7l4ty2j 258 1 We -PRON- PRP cord-002542-f7l4ty2j 258 2 pooled pool VBD cord-002542-f7l4ty2j 258 3 the the DT cord-002542-f7l4ty2j 258 4 amplified amplify VBN cord-002542-f7l4ty2j 258 5 cDNAs cDNAs NNPS cord-002542-f7l4ty2j 258 6 from from IN cord-002542-f7l4ty2j 258 7 each each DT cord-002542-f7l4ty2j 258 8 sample sample NN cord-002542-f7l4ty2j 258 9 at at IN cord-002542-f7l4ty2j 258 10 equimolar equimolar NNP cord-002542-f7l4ty2j 258 11 ratios ratio NNS cord-002542-f7l4ty2j 258 12 and and CC cord-002542-f7l4ty2j 258 13 loaded load VBD cord-002542-f7l4ty2j 258 14 the the DT cord-002542-f7l4ty2j 258 15 pooled pool VBN cord-002542-f7l4ty2j 258 16 , , , cord-002542-f7l4ty2j 258 17 barcoded barcoded JJ cord-002542-f7l4ty2j 258 18 library library NN cord-002542-f7l4ty2j 258 19 onto onto IN cord-002542-f7l4ty2j 258 20 a a DT cord-002542-f7l4ty2j 258 21 MinION MinION NNP cord-002542-f7l4ty2j 258 22 MkIB MkIB NNP cord-002542-f7l4ty2j 258 23 device device NN cord-002542-f7l4ty2j 258 24 using use VBG cord-002542-f7l4ty2j 258 25 an an DT cord-002542-f7l4ty2j 258 26 R9 R9 NNP cord-002542-f7l4ty2j 258 27 flowcell flowcell NNP cord-002542-f7l4ty2j 258 28 as as IN cord-002542-f7l4ty2j 258 29 per per IN cord-002542-f7l4ty2j 258 30 the the DT cord-002542-f7l4ty2j 258 31 manufacture manufacture NN cord-002542-f7l4ty2j 258 32 's 's POS cord-002542-f7l4ty2j 258 33 protocol protocol NN cord-002542-f7l4ty2j 258 34 . . . cord-002542-f7l4ty2j 259 1 We -PRON- PRP cord-002542-f7l4ty2j 259 2 ran run VBD cord-002542-f7l4ty2j 259 3 the the DT cord-002542-f7l4ty2j 259 4 standard standard JJ cord-002542-f7l4ty2j 259 5 protocol protocol NN cord-002542-f7l4ty2j 259 6 for for IN cord-002542-f7l4ty2j 259 7 obtaining obtain VBG cord-002542-f7l4ty2j 259 8 2-dimensional 2-dimensional JJ cord-002542-f7l4ty2j 259 9 reads read NNS cord-002542-f7l4ty2j 259 10 using use VBG cord-002542-f7l4ty2j 259 11 the the DT cord-002542-f7l4ty2j 259 12 MinKNOW minknow JJ cord-002542-f7l4ty2j 259 13 control control NN cord-002542-f7l4ty2j 259 14 software software NN cord-002542-f7l4ty2j 259 15 and and CC cord-002542-f7l4ty2j 259 16 collected collect VBD cord-002542-f7l4ty2j 259 17 nanopore nanopore NNP cord-002542-f7l4ty2j 259 18 reads read VBZ cord-002542-f7l4ty2j 259 19 for for IN cord-002542-f7l4ty2j 259 20 approximately approximately RB cord-002542-f7l4ty2j 259 21 36 36 CD cord-002542-f7l4ty2j 259 22 hours hour NNS cord-002542-f7l4ty2j 259 23 , , , cord-002542-f7l4ty2j 259 24 upon upon IN cord-002542-f7l4ty2j 259 25 which which WDT cord-002542-f7l4ty2j 259 26 the the DT cord-002542-f7l4ty2j 259 27 quality quality NN cord-002542-f7l4ty2j 259 28 and and CC cord-002542-f7l4ty2j 259 29 yield yield NN cord-002542-f7l4ty2j 259 30 of of IN cord-002542-f7l4ty2j 259 31 reads read NNS cord-002542-f7l4ty2j 259 32 dropped drop VBN cord-002542-f7l4ty2j 259 33 substantially substantially RB cord-002542-f7l4ty2j 259 34 . . . cord-002542-f7l4ty2j 260 1 We -PRON- PRP cord-002542-f7l4ty2j 260 2 obtained obtain VBD cord-002542-f7l4ty2j 260 3 a a DT cord-002542-f7l4ty2j 260 4 total total NN cord-002542-f7l4ty2j 260 5 of of IN cord-002542-f7l4ty2j 260 6 169'814 169'814 CD cord-002542-f7l4ty2j 260 7 reads read NNS cord-002542-f7l4ty2j 260 8 , , , cord-002542-f7l4ty2j 260 9 of of IN cord-002542-f7l4ty2j 260 10 which which WDT cord-002542-f7l4ty2j 260 11 46'183 46'183 CD cord-002542-f7l4ty2j 260 12 passed pass VBD cord-002542-f7l4ty2j 260 13 the the DT cord-002542-f7l4ty2j 260 14 default default NN cord-002542-f7l4ty2j 260 15 ONT ONT NNP cord-002542-f7l4ty2j 260 16 filter filter NN cord-002542-f7l4ty2j 260 17 and and CC cord-002542-f7l4ty2j 260 18 were be VBD cord-002542-f7l4ty2j 260 19 successfully successfully RB cord-002542-f7l4ty2j 260 20 demultiplexed demultiplexe VBN cord-002542-f7l4ty2j 260 21 . . . cord-002542-f7l4ty2j 261 1 This this DT cord-002542-f7l4ty2j 261 2 yielded yield VBD cord-002542-f7l4ty2j 261 3 between between IN cord-002542-f7l4ty2j 261 4 2688 2688 CD cord-002542-f7l4ty2j 261 5 and and CC cord-002542-f7l4ty2j 261 6 8815 8815 CD cord-002542-f7l4ty2j 261 7 full full JJ cord-002542-f7l4ty2j 261 8 - - HYPH cord-002542-f7l4ty2j 261 9 length length NN cord-002542-f7l4ty2j 261 10 reads read NNS cord-002542-f7l4ty2j 261 11 per per IN cord-002542-f7l4ty2j 261 12 passage passage NN cord-002542-f7l4ty2j 261 13 and and CC cord-002542-f7l4ty2j 261 14 corresponds correspond VBZ cord-002542-f7l4ty2j 261 15 to to IN cord-002542-f7l4ty2j 261 16 approximately approximately RB cord-002542-f7l4ty2j 261 17 0.1 0.1 CD cord-002542-f7l4ty2j 261 18 Gigabases gigabase NNS cord-002542-f7l4ty2j 261 19 of of IN cord-002542-f7l4ty2j 261 20 sequence sequence NN cord-002542-f7l4ty2j 261 21 information information NN cord-002542-f7l4ty2j 261 22 . . . cord-002542-f7l4ty2j 262 1 This this DT cord-002542-f7l4ty2j 262 2 would would MD cord-002542-f7l4ty2j 262 3 correspond correspond VB cord-002542-f7l4ty2j 262 4 to~80'000 to~80'000 WP cord-002542-f7l4ty2j 262 5 1x150bp 1x150bp CD cord-002542-f7l4ty2j 262 6 Illumina Illumina NNP cord-002542-f7l4ty2j 262 7 reads read VBZ cord-002542-f7l4ty2j 262 8 per per IN cord-002542-f7l4ty2j 262 9 sample sample NN cord-002542-f7l4ty2j 262 10 , , , cord-002542-f7l4ty2j 262 11 assuming assume VBG cord-002542-f7l4ty2j 262 12 even even RB cord-002542-f7l4ty2j 262 13 coverage coverage NN cord-002542-f7l4ty2j 262 14 . . . cord-002542-f7l4ty2j 263 1 With with IN cord-002542-f7l4ty2j 263 2 this this DT cord-002542-f7l4ty2j 263 3 depth depth NN cord-002542-f7l4ty2j 263 4 , , , cord-002542-f7l4ty2j 263 5 we -PRON- PRP cord-002542-f7l4ty2j 263 6 can can MD cord-002542-f7l4ty2j 263 7 build build VB cord-002542-f7l4ty2j 263 8 up up RP cord-002542-f7l4ty2j 263 9 a a DT cord-002542-f7l4ty2j 263 10 comprehensive comprehensive JJ cord-002542-f7l4ty2j 263 11 picture picture NN cord-002542-f7l4ty2j 263 12 of of IN cord-002542-f7l4ty2j 263 13 the the DT cord-002542-f7l4ty2j 263 14 full full JJ cord-002542-f7l4ty2j 263 15 - - HYPH cord-002542-f7l4ty2j 263 16 length length NN cord-002542-f7l4ty2j 263 17 genomic genomic JJ cord-002542-f7l4ty2j 263 18 landscape landscape NN cord-002542-f7l4ty2j 263 19 of of IN cord-002542-f7l4ty2j 263 20 the the DT cord-002542-f7l4ty2j 263 21 viral viral JJ cord-002542-f7l4ty2j 263 22 samples sample NNS cord-002542-f7l4ty2j 263 23 , , , cord-002542-f7l4ty2j 263 24 allowing allow VBG cord-002542-f7l4ty2j 263 25 us -PRON- PRP cord-002542-f7l4ty2j 263 26 to to TO cord-002542-f7l4ty2j 263 27 resolve resolve VB cord-002542-f7l4ty2j 263 28 DI DI NNP cord-002542-f7l4ty2j 263 29 - - HYPH cord-002542-f7l4ty2j 263 30 RNA RNA NNP cord-002542-f7l4ty2j 263 31 species specie NNS cord-002542-f7l4ty2j 263 32 even even RB cord-002542-f7l4ty2j 263 33 if if IN cord-002542-f7l4ty2j 263 34 they -PRON- PRP cord-002542-f7l4ty2j 263 35 were be VBD cord-002542-f7l4ty2j 263 36 present present JJ cord-002542-f7l4ty2j 263 37 at at IN cord-002542-f7l4ty2j 263 38 less less JJR cord-002542-f7l4ty2j 263 39 than than IN cord-002542-f7l4ty2j 263 40 1 1 CD cord-002542-f7l4ty2j 263 41 % % NN cord-002542-f7l4ty2j 263 42 of of IN cord-002542-f7l4ty2j 263 43 the the DT cord-002542-f7l4ty2j 263 44 total total JJ cord-002542-f7l4ty2j 263 45 viral viral JJ cord-002542-f7l4ty2j 263 46 genomic genomic JJ cord-002542-f7l4ty2j 263 47 population population NN cord-002542-f7l4ty2j 263 48 . . . cord-002542-f7l4ty2j 264 1 The the DT cord-002542-f7l4ty2j 264 2 long long RB cord-002542-f7l4ty2j 264 3 - - HYPH cord-002542-f7l4ty2j 264 4 read read VBN cord-002542-f7l4ty2j 264 5 nanopore nanopore NNP cord-002542-f7l4ty2j 264 6 sequencing sequencing NN cord-002542-f7l4ty2j 264 7 data datum NNS cord-002542-f7l4ty2j 264 8 were be VBD cord-002542-f7l4ty2j 264 9 aligned align VBN cord-002542-f7l4ty2j 264 10 to to IN cord-002542-f7l4ty2j 264 11 the the DT cord-002542-f7l4ty2j 264 12 full full JJ cord-002542-f7l4ty2j 264 13 - - HYPH cord-002542-f7l4ty2j 264 14 length length NN cord-002542-f7l4ty2j 264 15 FHV FHV NNP cord-002542-f7l4ty2j 264 16 genome genome NN cord-002542-f7l4ty2j 264 17 using use VBG cord-002542-f7l4ty2j 264 18 the the DT cord-002542-f7l4ty2j 264 19 BBMAP BBMAP NNP cord-002542-f7l4ty2j 264 20 suite suite NN cord-002542-f7l4ty2j 264 21 ( ( -LRB- cord-002542-f7l4ty2j 264 22 https://sourceforge.net/projects/bbmap/ https://sourceforge.net/projects/bbmap/ NNP cord-002542-f7l4ty2j 264 23 ) ) -RRB- cord-002542-f7l4ty2j 264 24 . . . cord-002542-f7l4ty2j 265 1 This this DT cord-002542-f7l4ty2j 265 2 pipeline pipeline NN cord-002542-f7l4ty2j 265 3 tolerates tolerate VBZ cord-002542-f7l4ty2j 265 4 large large JJ cord-002542-f7l4ty2j 265 5 insertions insertion NNS cord-002542-f7l4ty2j 265 6 and and CC cord-002542-f7l4ty2j 265 7 deletions deletion NNS cord-002542-f7l4ty2j 265 8 in in IN cord-002542-f7l4ty2j 265 9 the the DT cord-002542-f7l4ty2j 265 10 long long RB cord-002542-f7l4ty2j 265 11 - - HYPH cord-002542-f7l4ty2j 265 12 reads read NNS cord-002542-f7l4ty2j 265 13 , , , cord-002542-f7l4ty2j 265 14 thus thus RB cord-002542-f7l4ty2j 265 15 allowing allow VBG cord-002542-f7l4ty2j 265 16 us -PRON- PRP cord-002542-f7l4ty2j 265 17 to to TO cord-002542-f7l4ty2j 265 18 characterize characterize VB cord-002542-f7l4ty2j 265 19 the the DT cord-002542-f7l4ty2j 265 20 overall overall JJ cord-002542-f7l4ty2j 265 21 topology topology NN cord-002542-f7l4ty2j 265 22 of of IN cord-002542-f7l4ty2j 265 23 the the DT cord-002542-f7l4ty2j 265 24 defective defective JJ cord-002542-f7l4ty2j 265 25 RNAs rna NNS cord-002542-f7l4ty2j 265 26 . . . cord-002542-f7l4ty2j 266 1 We -PRON- PRP cord-002542-f7l4ty2j 266 2 mapped map VBD cord-002542-f7l4ty2j 266 3 between between IN cord-002542-f7l4ty2j 266 4 94 94 CD cord-002542-f7l4ty2j 266 5 and and CC cord-002542-f7l4ty2j 266 6 97.5 97.5 CD cord-002542-f7l4ty2j 266 7 % % NN cord-002542-f7l4ty2j 266 8 of of IN cord-002542-f7l4ty2j 266 9 the the DT cord-002542-f7l4ty2j 266 10 MinION minion XX cord-002542-f7l4ty2j 266 11 reads read VBZ cord-002542-f7l4ty2j 266 12 from from IN cord-002542-f7l4ty2j 266 13 each each DT cord-002542-f7l4ty2j 266 14 passage passage NN cord-002542-f7l4ty2j 266 15 to to IN cord-002542-f7l4ty2j 266 16 the the DT cord-002542-f7l4ty2j 266 17 FHV FHV NNP cord-002542-f7l4ty2j 266 18 reference reference NN cord-002542-f7l4ty2j 266 19 genome genome NN cord-002542-f7l4ty2j 266 20 ( ( -LRB- cord-002542-f7l4ty2j 266 21 Table Table NNP cord-002542-f7l4ty2j 266 22 3 3 CD cord-002542-f7l4ty2j 266 23 ) ) -RRB- cord-002542-f7l4ty2j 266 24 . . . cord-002542-f7l4ty2j 267 1 An an DT cord-002542-f7l4ty2j 267 2 example example NN cord-002542-f7l4ty2j 267 3 of of IN cord-002542-f7l4ty2j 267 4 reads read NNS cord-002542-f7l4ty2j 267 5 aligned align VBN cord-002542-f7l4ty2j 267 6 to to IN cord-002542-f7l4ty2j 267 7 FHV FHV NNP cord-002542-f7l4ty2j 267 8 RNA2 RNA2 NNP cord-002542-f7l4ty2j 267 9 is be VBZ cord-002542-f7l4ty2j 267 10 shown show VBN cord-002542-f7l4ty2j 267 11 in in IN cord-002542-f7l4ty2j 267 12 S4 S4 NNP cord-002542-f7l4ty2j 267 13 Fig Fig NNP cord-002542-f7l4ty2j 267 14 . . . cord-002542-f7l4ty2j 268 1 The the DT cord-002542-f7l4ty2j 268 2 error error NN cord-002542-f7l4ty2j 268 3 rate rate NN cord-002542-f7l4ty2j 268 4 of of IN cord-002542-f7l4ty2j 268 5 aligned align VBN cord-002542-f7l4ty2j 268 6 reads read VBZ cord-002542-f7l4ty2j 268 7 , , , cord-002542-f7l4ty2j 268 8 including include VBG cord-002542-f7l4ty2j 268 9 single single JJ cord-002542-f7l4ty2j 268 10 nucleotide nucleotide JJ cord-002542-f7l4ty2j 268 11 mismatches mismatch NNS cord-002542-f7l4ty2j 268 12 and and CC cord-002542-f7l4ty2j 268 13 small small JJ cord-002542-f7l4ty2j 268 14 InDels InDels NNPS cord-002542-f7l4ty2j 268 15 , , , cord-002542-f7l4ty2j 268 16 was be VBD cord-002542-f7l4ty2j 268 17 determined determine VBN cord-002542-f7l4ty2j 268 18 from from IN cord-002542-f7l4ty2j 268 19 alignment alignment NN cord-002542-f7l4ty2j 268 20 pileup pileup NN cord-002542-f7l4ty2j 268 21 files file NNS cord-002542-f7l4ty2j 268 22 . . . cord-002542-f7l4ty2j 269 1 Consistent consistent JJ cord-002542-f7l4ty2j 269 2 with with IN cord-002542-f7l4ty2j 269 3 recent recent JJ cord-002542-f7l4ty2j 269 4 reports report NNS cord-002542-f7l4ty2j 269 5 [ [ -LRB- cord-002542-f7l4ty2j 269 6 66 66 CD cord-002542-f7l4ty2j 269 7 ] ] -RRB- cord-002542-f7l4ty2j 269 8 , , , cord-002542-f7l4ty2j 269 9 we -PRON- PRP cord-002542-f7l4ty2j 269 10 found find VBD cord-002542-f7l4ty2j 269 11 the the DT cord-002542-f7l4ty2j 269 12 overall overall JJ cord-002542-f7l4ty2j 269 13 modal modal JJ cord-002542-f7l4ty2j 269 14 and and CC cord-002542-f7l4ty2j 269 15 mean mean JJ cord-002542-f7l4ty2j 269 16 error error NN cord-002542-f7l4ty2j 269 17 rates rate NNS cord-002542-f7l4ty2j 269 18 for for IN cord-002542-f7l4ty2j 269 19 all all DT cord-002542-f7l4ty2j 269 20 mapped map VBN cord-002542-f7l4ty2j 269 21 position position NN cord-002542-f7l4ty2j 269 22 was be VBD cord-002542-f7l4ty2j 269 23 5.0 5.0 CD cord-002542-f7l4ty2j 269 24 % % NN cord-002542-f7l4ty2j 269 25 and and CC cord-002542-f7l4ty2j 269 26 6.3 6.3 CD cord-002542-f7l4ty2j 269 27 % % NN cord-002542-f7l4ty2j 269 28 respectively respectively RB cord-002542-f7l4ty2j 269 29 , , , cord-002542-f7l4ty2j 269 30 with with IN cord-002542-f7l4ty2j 269 31 95 95 CD cord-002542-f7l4ty2j 269 32 % % NN cord-002542-f7l4ty2j 269 33 of of IN cord-002542-f7l4ty2j 269 34 the the DT cord-002542-f7l4ty2j 269 35 sites site NNS cord-002542-f7l4ty2j 269 36 having have VBG cord-002542-f7l4ty2j 269 37 an an DT cord-002542-f7l4ty2j 269 38 error error NN cord-002542-f7l4ty2j 269 39 rate rate NN cord-002542-f7l4ty2j 269 40 better well JJR cord-002542-f7l4ty2j 269 41 than than IN cord-002542-f7l4ty2j 269 42 13.6 13.6 CD cord-002542-f7l4ty2j 269 43 % % NN cord-002542-f7l4ty2j 270 1 ( ( -LRB- cord-002542-f7l4ty2j 270 2 N95 N95 NNP cord-002542-f7l4ty2j 270 3 value value NN cord-002542-f7l4ty2j 270 4 = = SYM cord-002542-f7l4ty2j 270 5 0.864 0.864 CD cord-002542-f7l4ty2j 270 6 ) ) -RRB- cord-002542-f7l4ty2j 270 7 . . . cord-002542-f7l4ty2j 271 1 Example example NN cord-002542-f7l4ty2j 271 2 of of IN cord-002542-f7l4ty2j 271 3 how how WRB cord-002542-f7l4ty2j 271 4 reads read VBZ cord-002542-f7l4ty2j 271 5 generated generate VBN cord-002542-f7l4ty2j 271 6 from from IN cord-002542-f7l4ty2j 271 7 the the DT cord-002542-f7l4ty2j 271 8 Illumina Illumina NNP cord-002542-f7l4ty2j 271 9 HiSeq HiSeq NNP cord-002542-f7l4ty2j 271 10 would would MD cord-002542-f7l4ty2j 271 11 map map VB cord-002542-f7l4ty2j 271 12 to to IN cord-002542-f7l4ty2j 271 13 a a DT cord-002542-f7l4ty2j 271 14 reference reference NN cord-002542-f7l4ty2j 271 15 genome genome NN cord-002542-f7l4ty2j 271 16 . . . cord-002542-f7l4ty2j 272 1 The the DT cord-002542-f7l4ty2j 272 2 Bowtie Bowtie NNP cord-002542-f7l4ty2j 272 3 alignment alignment NN cord-002542-f7l4ty2j 272 4 is be VBZ cord-002542-f7l4ty2j 272 5 able able JJ cord-002542-f7l4ty2j 272 6 to to TO cord-002542-f7l4ty2j 272 7 map map VB cord-002542-f7l4ty2j 272 8 150bp 150bp NNP cord-002542-f7l4ty2j 272 9 reads read VBZ cord-002542-f7l4ty2j 272 10 along along IN cord-002542-f7l4ty2j 272 11 the the DT cord-002542-f7l4ty2j 272 12 reference reference NN cord-002542-f7l4ty2j 272 13 with with IN cord-002542-f7l4ty2j 272 14 a a DT cord-002542-f7l4ty2j 272 15 relatively relatively RB cord-002542-f7l4ty2j 272 16 even even JJ cord-002542-f7l4ty2j 272 17 coverage coverage NN cord-002542-f7l4ty2j 272 18 distribution distribution NN cord-002542-f7l4ty2j 272 19 . . . cord-002542-f7l4ty2j 273 1 Unmapped unmapped JJ cord-002542-f7l4ty2j 273 2 reads read NNS cord-002542-f7l4ty2j 273 3 are be VBP cord-002542-f7l4ty2j 273 4 then then RB cord-002542-f7l4ty2j 273 5 aligned align VBN cord-002542-f7l4ty2j 273 6 with with IN cord-002542-f7l4ty2j 273 7 ViReMa virema NN cord-002542-f7l4ty2j 273 8 to to TO cord-002542-f7l4ty2j 273 9 accurately accurately RB cord-002542-f7l4ty2j 273 10 identify identify VB cord-002542-f7l4ty2j 273 11 recombination recombination NN cord-002542-f7l4ty2j 273 12 events event NNS cord-002542-f7l4ty2j 273 13 . . . cord-002542-f7l4ty2j 274 1 The the DT cord-002542-f7l4ty2j 274 2 low low JJ cord-002542-f7l4ty2j 274 3 error error NN cord-002542-f7l4ty2j 274 4 rate rate NN cord-002542-f7l4ty2j 274 5 of of IN cord-002542-f7l4ty2j 274 6 highthroughput highthroughput NN cord-002542-f7l4ty2j 274 7 sequencing sequencing NN cord-002542-f7l4ty2j 274 8 allows allow VBZ cord-002542-f7l4ty2j 274 9 us -PRON- PRP cord-002542-f7l4ty2j 274 10 to to TO cord-002542-f7l4ty2j 274 11 precisely precisely RB cord-002542-f7l4ty2j 274 12 define define VB cord-002542-f7l4ty2j 274 13 the the DT cord-002542-f7l4ty2j 274 14 boundaries boundary NNS cord-002542-f7l4ty2j 274 15 of of IN cord-002542-f7l4ty2j 274 16 the the DT cord-002542-f7l4ty2j 274 17 junctions junction NNS cord-002542-f7l4ty2j 274 18 . . . cord-002542-f7l4ty2j 275 1 Below below IN cord-002542-f7l4ty2j 275 2 the the DT cord-002542-f7l4ty2j 275 3 reference reference NN cord-002542-f7l4ty2j 275 4 genome genome NN cord-002542-f7l4ty2j 275 5 is be VBZ cord-002542-f7l4ty2j 275 6 an an DT cord-002542-f7l4ty2j 275 7 example example NN cord-002542-f7l4ty2j 275 8 of of IN cord-002542-f7l4ty2j 275 9 how how WRB cord-002542-f7l4ty2j 275 10 reads read VBZ cord-002542-f7l4ty2j 275 11 generated generate VBN cord-002542-f7l4ty2j 275 12 from from IN cord-002542-f7l4ty2j 275 13 Oxford Oxford NNP cord-002542-f7l4ty2j 275 14 Nanopore Nanopore NNP cord-002542-f7l4ty2j 275 15 Technologies Technologies NNPS cord-002542-f7l4ty2j 275 16 's 's POS cord-002542-f7l4ty2j 275 17 MinION minion NN cord-002542-f7l4ty2j 275 18 sequencing sequencing NN cord-002542-f7l4ty2j 275 19 would would MD cord-002542-f7l4ty2j 275 20 map map VB cord-002542-f7l4ty2j 275 21 to to IN cord-002542-f7l4ty2j 275 22 a a DT cord-002542-f7l4ty2j 275 23 reference reference NN cord-002542-f7l4ty2j 275 24 genome genome NN cord-002542-f7l4ty2j 275 25 . . . cord-002542-f7l4ty2j 276 1 The the DT cord-002542-f7l4ty2j 276 2 MinION minion NN cord-002542-f7l4ty2j 276 3 is be VBZ cord-002542-f7l4ty2j 276 4 able able JJ cord-002542-f7l4ty2j 276 5 to to TO cord-002542-f7l4ty2j 276 6 generate generate VB cord-002542-f7l4ty2j 276 7 full full JJ cord-002542-f7l4ty2j 276 8 length length NN cord-002542-f7l4ty2j 276 9 reads read VBZ cord-002542-f7l4ty2j 276 10 at at IN cord-002542-f7l4ty2j 276 11 the the DT cord-002542-f7l4ty2j 276 12 expense expense NN cord-002542-f7l4ty2j 276 13 of of IN cord-002542-f7l4ty2j 276 14 a a DT cord-002542-f7l4ty2j 276 15 high high JJ cord-002542-f7l4ty2j 276 16 error error NN cord-002542-f7l4ty2j 276 17 rate rate NN cord-002542-f7l4ty2j 276 18 , , , cord-002542-f7l4ty2j 276 19 which which WDT cord-002542-f7l4ty2j 276 20 is~7 is~7 NNP cord-002542-f7l4ty2j 276 21 % % NN cord-002542-f7l4ty2j 276 22 . . . cord-002542-f7l4ty2j 277 1 Full full JJ cord-002542-f7l4ty2j 277 2 length length NN cord-002542-f7l4ty2j 277 3 analysis analysis NN cord-002542-f7l4ty2j 277 4 allows allow VBZ cord-002542-f7l4ty2j 277 5 us -PRON- PRP cord-002542-f7l4ty2j 277 6 to to TO cord-002542-f7l4ty2j 277 7 determine determine VB cord-002542-f7l4ty2j 277 8 what what WP cord-002542-f7l4ty2j 277 9 recombination recombination NN cord-002542-f7l4ty2j 277 10 events event VBZ cord-002542-f7l4ty2j 277 11 a a DT cord-002542-f7l4ty2j 277 12 genome genome NN cord-002542-f7l4ty2j 277 13 contains contain VBZ cord-002542-f7l4ty2j 277 14 . . . cord-002542-f7l4ty2j 278 1 Due due IN cord-002542-f7l4ty2j 278 2 to to IN cord-002542-f7l4ty2j 278 3 the the DT cord-002542-f7l4ty2j 278 4 error error NN cord-002542-f7l4ty2j 278 5 rate rate NN cord-002542-f7l4ty2j 278 6 the the DT cord-002542-f7l4ty2j 278 7 exact exact JJ cord-002542-f7l4ty2j 278 8 boundaries boundary NNS cord-002542-f7l4ty2j 278 9 of of IN cord-002542-f7l4ty2j 278 10 the the DT cord-002542-f7l4ty2j 278 11 recombination recombination NN cord-002542-f7l4ty2j 278 12 event event NN cord-002542-f7l4ty2j 278 13 are be VBP cord-002542-f7l4ty2j 278 14 imprecise imprecise JJ cord-002542-f7l4ty2j 278 15 . . . cord-002542-f7l4ty2j 279 1 ( ( -LRB- cord-002542-f7l4ty2j 279 2 S5B S5B NNP cord-002542-f7l4ty2j 279 3 and and CC cord-002542-f7l4ty2j 279 4 S5C S5C NNP cord-002542-f7l4ty2j 279 5 Fig Fig NNP cord-002542-f7l4ty2j 279 6 ) ) -RRB- cord-002542-f7l4ty2j 279 7 . . . cord-002542-f7l4ty2j 280 1 This this DT cord-002542-f7l4ty2j 280 2 shows show VBZ cord-002542-f7l4ty2j 280 3 that that IN cord-002542-f7l4ty2j 280 4 small small JJ cord-002542-f7l4ty2j 280 5 InDels InDels NNPS cord-002542-f7l4ty2j 280 6 are be VBP cord-002542-f7l4ty2j 280 7 frequent frequent JJ cord-002542-f7l4ty2j 280 8 , , , cord-002542-f7l4ty2j 280 9 but but CC cord-002542-f7l4ty2j 280 10 fall fall VB cord-002542-f7l4ty2j 280 11 quickly quickly RB cord-002542-f7l4ty2j 280 12 in in IN cord-002542-f7l4ty2j 280 13 abundance abundance NN cord-002542-f7l4ty2j 280 14 with with IN cord-002542-f7l4ty2j 280 15 increasing increase VBG cord-002542-f7l4ty2j 280 16 length length NN cord-002542-f7l4ty2j 280 17 . . . cord-002542-f7l4ty2j 281 1 99.8 99.8 CD cord-002542-f7l4ty2j 281 2 % % NN cord-002542-f7l4ty2j 281 3 and and CC cord-002542-f7l4ty2j 281 4 99.9 99.9 CD cord-002542-f7l4ty2j 281 5 % % NN cord-002542-f7l4ty2j 281 6 of of IN cord-002542-f7l4ty2j 281 7 all all DT cord-002542-f7l4ty2j 281 8 MinION minion NN cord-002542-f7l4ty2j 281 9 deletions deletion NNS cord-002542-f7l4ty2j 281 10 and and CC cord-002542-f7l4ty2j 281 11 insertions insertion NNS cord-002542-f7l4ty2j 281 12 respectively respectively RB cord-002542-f7l4ty2j 281 13 were be VBD cord-002542-f7l4ty2j 281 14 shorter short JJR cord-002542-f7l4ty2j 281 15 than than IN cord-002542-f7l4ty2j 281 16 25nts 25nt NNS cord-002542-f7l4ty2j 281 17 . . . cord-002542-f7l4ty2j 282 1 Therefore therefore RB cord-002542-f7l4ty2j 282 2 , , , cord-002542-f7l4ty2j 282 3 we -PRON- PRP cord-002542-f7l4ty2j 282 4 considered consider VBD cord-002542-f7l4ty2j 282 5 only only JJ cord-002542-f7l4ty2j 282 6 deletions deletion NNS cord-002542-f7l4ty2j 282 7 and and CC cord-002542-f7l4ty2j 282 8 insertions insertion NNS cord-002542-f7l4ty2j 282 9 of of IN cord-002542-f7l4ty2j 282 10 at at RB cord-002542-f7l4ty2j 282 11 least least JJS cord-002542-f7l4ty2j 282 12 25nts 25nts CD cord-002542-f7l4ty2j 282 13 to to TO cord-002542-f7l4ty2j 282 14 be be VB cord-002542-f7l4ty2j 282 15 likely likely JJ cord-002542-f7l4ty2j 282 16 to to TO cord-002542-f7l4ty2j 282 17 be be VB cord-002542-f7l4ty2j 282 18 bona bona JJ cord-002542-f7l4ty2j 282 19 fide fide JJ cord-002542-f7l4ty2j 282 20 InDels InDels NNPS cord-002542-f7l4ty2j 282 21 present present JJ cord-002542-f7l4ty2j 282 22 in in IN cord-002542-f7l4ty2j 282 23 the the DT cord-002542-f7l4ty2j 282 24 original original JJ cord-002542-f7l4ty2j 282 25 viral viral JJ cord-002542-f7l4ty2j 282 26 RNA RNA NNP cord-002542-f7l4ty2j 282 27 and and CC cord-002542-f7l4ty2j 282 28 corresponding correspond VBG cord-002542-f7l4ty2j 282 29 to to IN cord-002542-f7l4ty2j 282 30 recombination recombination NN cord-002542-f7l4ty2j 282 31 events event NNS cord-002542-f7l4ty2j 282 32 comprising comprise VBG cord-002542-f7l4ty2j 282 33 defective defective JJ cord-002542-f7l4ty2j 282 34 RNA RNA NNP cord-002542-f7l4ty2j 282 35 species specie NNS cord-002542-f7l4ty2j 282 36 rather rather RB cord-002542-f7l4ty2j 282 37 than than IN cord-002542-f7l4ty2j 282 38 a a DT cord-002542-f7l4ty2j 282 39 sequencing sequencing NN cord-002542-f7l4ty2j 282 40 error error NN cord-002542-f7l4ty2j 282 41 . . . cord-002542-f7l4ty2j 283 1 The the DT cord-002542-f7l4ty2j 283 2 nanopore nanopore NNP cord-002542-f7l4ty2j 283 3 data data NN cord-002542-f7l4ty2j 283 4 reveals reveal VBZ cord-002542-f7l4ty2j 283 5 the the DT cord-002542-f7l4ty2j 283 6 presence presence NN cord-002542-f7l4ty2j 283 7 and and CC cord-002542-f7l4ty2j 283 8 frequency frequency NN cord-002542-f7l4ty2j 283 9 of of IN cord-002542-f7l4ty2j 283 10 large large JJ cord-002542-f7l4ty2j 283 11 deletions deletion NNS cord-002542-f7l4ty2j 283 12 and and CC cord-002542-f7l4ty2j 283 13 insertions insertion NNS cord-002542-f7l4ty2j 283 14 within within IN cord-002542-f7l4ty2j 283 15 defective defective JJ cord-002542-f7l4ty2j 283 16 RNA RNA NNP cord-002542-f7l4ty2j 283 17 genomes genome NNS cord-002542-f7l4ty2j 283 18 . . . cord-002542-f7l4ty2j 284 1 From from IN cord-002542-f7l4ty2j 284 2 these these DT cord-002542-f7l4ty2j 284 3 , , , cord-002542-f7l4ty2j 284 4 we -PRON- PRP cord-002542-f7l4ty2j 284 5 can can MD cord-002542-f7l4ty2j 284 6 reconstruct reconstruct VB cord-002542-f7l4ty2j 284 7 the the DT cord-002542-f7l4ty2j 284 8 population population NN cord-002542-f7l4ty2j 284 9 of of IN cord-002542-f7l4ty2j 284 10 either either DT cord-002542-f7l4ty2j 284 11 full full JJ cord-002542-f7l4ty2j 284 12 - - HYPH cord-002542-f7l4ty2j 284 13 length length NN cord-002542-f7l4ty2j 284 14 or or CC cord-002542-f7l4ty2j 284 15 defective defective JJ cord-002542-f7l4ty2j 284 16 RNA RNA NNP cord-002542-f7l4ty2j 284 17 genomes genome NNS cord-002542-f7l4ty2j 284 18 present present JJ cord-002542-f7l4ty2j 284 19 in in IN cord-002542-f7l4ty2j 284 20 each each DT cord-002542-f7l4ty2j 284 21 of of IN cord-002542-f7l4ty2j 284 22 the the DT cord-002542-f7l4ty2j 284 23 viral viral JJ cord-002542-f7l4ty2j 284 24 passages passage NNS cord-002542-f7l4ty2j 284 25 ( ( -LRB- cord-002542-f7l4ty2j 284 26 annotated annotate VBN cord-002542-f7l4ty2j 284 27 as as IN cord-002542-f7l4ty2j 284 28 described describe VBN cord-002542-f7l4ty2j 284 29 in in IN cord-002542-f7l4ty2j 284 30 the the DT cord-002542-f7l4ty2j 284 31 Methods Methods NNPS cord-002542-f7l4ty2j 284 32 section section NN cord-002542-f7l4ty2j 284 33 ) ) -RRB- cord-002542-f7l4ty2j 284 34 . . . cord-002542-f7l4ty2j 285 1 The the DT cord-002542-f7l4ty2j 285 2 full full JJ cord-002542-f7l4ty2j 285 3 table table NN cord-002542-f7l4ty2j 285 4 of of IN cord-002542-f7l4ty2j 285 5 characterized characterize VBN cord-002542-f7l4ty2j 285 6 defective defective JJ cord-002542-f7l4ty2j 285 7 RNAs rna NNS cord-002542-f7l4ty2j 285 8 and and CC cord-002542-f7l4ty2j 285 9 their -PRON- PRP$ cord-002542-f7l4ty2j 285 10 frequencies frequency NNS cord-002542-f7l4ty2j 285 11 in in IN cord-002542-f7l4ty2j 285 12 each each DT cord-002542-f7l4ty2j 285 13 passage passage NN cord-002542-f7l4ty2j 285 14 is be VBZ cord-002542-f7l4ty2j 285 15 detailed detail VBN cord-002542-f7l4ty2j 285 16 in in IN cord-002542-f7l4ty2j 285 17 S2 S2 NNP cord-002542-f7l4ty2j 285 18 Datafile Datafile NNP cord-002542-f7l4ty2j 285 19 . . . cord-002542-f7l4ty2j 286 1 In in IN cord-002542-f7l4ty2j 286 2 total total NN cord-002542-f7l4ty2j 286 3 , , , cord-002542-f7l4ty2j 286 4 we -PRON- PRP cord-002542-f7l4ty2j 286 5 found find VBD cord-002542-f7l4ty2j 286 6 6030 6030 CD cord-002542-f7l4ty2j 286 7 and and CC cord-002542-f7l4ty2j 286 8 3639 3639 CD cord-002542-f7l4ty2j 286 9 unique unique JJ cord-002542-f7l4ty2j 286 10 defective defective JJ cord-002542-f7l4ty2j 286 11 RNAs rna NNS cord-002542-f7l4ty2j 286 12 of of IN cord-002542-f7l4ty2j 286 13 RNA1 RNA1 NNP cord-002542-f7l4ty2j 286 14 and and CC cord-002542-f7l4ty2j 286 15 RNA2 RNA2 NNP cord-002542-f7l4ty2j 286 16 respectively respectively RB cord-002542-f7l4ty2j 286 17 throughout throughout IN cord-002542-f7l4ty2j 286 18 all all DT cord-002542-f7l4ty2j 286 19 passages passage NNS cord-002542-f7l4ty2j 286 20 . . . cord-002542-f7l4ty2j 287 1 The the DT cord-002542-f7l4ty2j 287 2 frequency frequency NN cord-002542-f7l4ty2j 287 3 of of IN cord-002542-f7l4ty2j 287 4 individual individual JJ cord-002542-f7l4ty2j 287 5 recombination recombination NN cord-002542-f7l4ty2j 287 6 events event NNS cord-002542-f7l4ty2j 287 7 found find VBN cord-002542-f7l4ty2j 287 8 in in IN cord-002542-f7l4ty2j 287 9 both both CC cord-002542-f7l4ty2j 287 10 the the DT cord-002542-f7l4ty2j 287 11 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 287 12 data datum NNS cord-002542-f7l4ty2j 287 13 and and CC cord-002542-f7l4ty2j 287 14 the the DT cord-002542-f7l4ty2j 287 15 MinION MinION NNP cord-002542-f7l4ty2j 287 16 data datum NNS cord-002542-f7l4ty2j 287 17 were be VBD cord-002542-f7l4ty2j 287 18 compared compare VBN cord-002542-f7l4ty2j 287 19 and and CC cord-002542-f7l4ty2j 287 20 correlation correlation NN cord-002542-f7l4ty2j 287 21 coefficients coefficient NNS cord-002542-f7l4ty2j 287 22 calculated calculate VBN cord-002542-f7l4ty2j 287 23 ( ( -LRB- cord-002542-f7l4ty2j 287 24 Table Table NNP cord-002542-f7l4ty2j 287 25 3 3 CD cord-002542-f7l4ty2j 287 26 ) ) -RRB- cord-002542-f7l4ty2j 287 27 . . . cord-002542-f7l4ty2j 288 1 The the DT cord-002542-f7l4ty2j 288 2 correlation correlation NN cord-002542-f7l4ty2j 288 3 in in IN cord-002542-f7l4ty2j 288 4 the the DT cord-002542-f7l4ty2j 288 5 earliest early JJS cord-002542-f7l4ty2j 288 6 passages passage NNS cord-002542-f7l4ty2j 288 7 was be VBD cord-002542-f7l4ty2j 288 8 poor poor JJ cord-002542-f7l4ty2j 288 9 , , , cord-002542-f7l4ty2j 288 10 due due IN cord-002542-f7l4ty2j 288 11 to to IN cord-002542-f7l4ty2j 288 12 the the DT cord-002542-f7l4ty2j 288 13 low low JJ cord-002542-f7l4ty2j 288 14 abundance abundance NN cord-002542-f7l4ty2j 288 15 of of IN cord-002542-f7l4ty2j 288 16 events event NNS cord-002542-f7l4ty2j 288 17 in in IN cord-002542-f7l4ty2j 288 18 both both DT cord-002542-f7l4ty2j 288 19 datasets dataset NNS cord-002542-f7l4ty2j 288 20 . . . cord-002542-f7l4ty2j 289 1 However however RB cord-002542-f7l4ty2j 289 2 , , , cord-002542-f7l4ty2j 289 3 later later RB cord-002542-f7l4ty2j 289 4 passages passage NNS cord-002542-f7l4ty2j 289 5 correlate correlate VBP cord-002542-f7l4ty2j 289 6 well well RB cord-002542-f7l4ty2j 289 7 with with IN cord-002542-f7l4ty2j 289 8 Pearson Pearson NNP cord-002542-f7l4ty2j 289 9 coefficients coefficient NNS cord-002542-f7l4ty2j 289 10 reaching reach VBG cord-002542-f7l4ty2j 289 11 0.85 0.85 CD cord-002542-f7l4ty2j 289 12 . . . cord-002542-f7l4ty2j 290 1 This this DT cord-002542-f7l4ty2j 290 2 is be VBZ cord-002542-f7l4ty2j 290 3 important important JJ cord-002542-f7l4ty2j 290 4 as as IN cord-002542-f7l4ty2j 290 5 it -PRON- PRP cord-002542-f7l4ty2j 290 6 demonstrates demonstrate VBZ cord-002542-f7l4ty2j 290 7 that that IN cord-002542-f7l4ty2j 290 8 the the DT cord-002542-f7l4ty2j 290 9 frequency frequency NN cord-002542-f7l4ty2j 290 10 of of IN cord-002542-f7l4ty2j 290 11 recombination recombination NN cord-002542-f7l4ty2j 290 12 events event NNS cord-002542-f7l4ty2j 290 13 was be VBD cord-002542-f7l4ty2j 290 14 not not RB cord-002542-f7l4ty2j 290 15 biased bias VBN cord-002542-f7l4ty2j 290 16 during during IN cord-002542-f7l4ty2j 290 17 cDNA cdna NN cord-002542-f7l4ty2j 290 18 amplification amplification NN cord-002542-f7l4ty2j 290 19 of of IN cord-002542-f7l4ty2j 290 20 the the DT cord-002542-f7l4ty2j 290 21 full full JJ cord-002542-f7l4ty2j 290 22 - - HYPH cord-002542-f7l4ty2j 290 23 length length NN cord-002542-f7l4ty2j 290 24 or or CC cord-002542-f7l4ty2j 290 25 defective defective JJ cord-002542-f7l4ty2j 290 26 viral viral JJ cord-002542-f7l4ty2j 290 27 genomes genome NNS cord-002542-f7l4ty2j 290 28 . . . cord-002542-f7l4ty2j 291 1 Similarly similarly RB cord-002542-f7l4ty2j 291 2 , , , cord-002542-f7l4ty2j 291 3 the the DT cord-002542-f7l4ty2j 291 4 Shannon Shannon NNP cord-002542-f7l4ty2j 291 5 Entropy Entropy NNP cord-002542-f7l4ty2j 291 6 indices index NNS cord-002542-f7l4ty2j 291 7 increase increase VBP cord-002542-f7l4ty2j 291 8 during during IN cord-002542-f7l4ty2j 291 9 passaging passage VBG cord-002542-f7l4ty2j 291 10 ( ( -LRB- cord-002542-f7l4ty2j 291 11 Fig Fig NNP cord-002542-f7l4ty2j 291 12 5C 5c CD cord-002542-f7l4ty2j 291 13 ) ) -RRB- cord-002542-f7l4ty2j 291 14 , , , cord-002542-f7l4ty2j 291 15 consistent consistent JJ cord-002542-f7l4ty2j 291 16 with with IN cord-002542-f7l4ty2j 291 17 those those DT cord-002542-f7l4ty2j 291 18 from from IN cord-002542-f7l4ty2j 291 19 the the DT cord-002542-f7l4ty2j 291 20 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 291 21 data datum NNS cord-002542-f7l4ty2j 291 22 . . . cord-002542-f7l4ty2j 292 1 The the DT cord-002542-f7l4ty2j 292 2 number number NN cord-002542-f7l4ty2j 292 3 of of IN cord-002542-f7l4ty2j 292 4 deletions deletion NNS cord-002542-f7l4ty2j 292 5 in in IN cord-002542-f7l4ty2j 292 6 each each DT cord-002542-f7l4ty2j 292 7 passage passage NN cord-002542-f7l4ty2j 292 8 in in IN cord-002542-f7l4ty2j 292 9 RNA1 RNA1 NNP cord-002542-f7l4ty2j 292 10 and and CC cord-002542-f7l4ty2j 292 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 292 12 are be VBP cord-002542-f7l4ty2j 292 13 given give VBN cord-002542-f7l4ty2j 292 14 in in IN cord-002542-f7l4ty2j 292 15 Table Table NNP cord-002542-f7l4ty2j 292 16 3 3 CD cord-002542-f7l4ty2j 292 17 and and CC cord-002542-f7l4ty2j 292 18 illustrated illustrate VBN cord-002542-f7l4ty2j 292 19 in in IN cord-002542-f7l4ty2j 292 20 Fig Fig NNP cord-002542-f7l4ty2j 292 21 5B. 5B. NNP cord-002542-f7l4ty2j 293 1 The the DT cord-002542-f7l4ty2j 293 2 earliest early JJS cord-002542-f7l4ty2j 293 3 passage passage NN cord-002542-f7l4ty2j 293 4 contains contain VBZ cord-002542-f7l4ty2j 293 5 very very RB cord-002542-f7l4ty2j 293 6 few few JJ cord-002542-f7l4ty2j 293 7 deletions deletion NNS cord-002542-f7l4ty2j 293 8 . . . cord-002542-f7l4ty2j 294 1 In in IN cord-002542-f7l4ty2j 294 2 passage passage NN cord-002542-f7l4ty2j 294 3 1 1 CD cord-002542-f7l4ty2j 294 4 , , , cord-002542-f7l4ty2j 294 5 95.8 95.8 CD cord-002542-f7l4ty2j 294 6 % % NN cord-002542-f7l4ty2j 294 7 of of IN cord-002542-f7l4ty2j 294 8 the the DT cord-002542-f7l4ty2j 294 9 reads read NNS cord-002542-f7l4ty2j 294 10 map map NN cord-002542-f7l4ty2j 294 11 to to IN cord-002542-f7l4ty2j 294 12 the the DT cord-002542-f7l4ty2j 294 13 full full JJ cord-002542-f7l4ty2j 294 14 - - HYPH cord-002542-f7l4ty2j 294 15 length length NN cord-002542-f7l4ty2j 294 16 genome genome NN cord-002542-f7l4ty2j 294 17 in in IN cord-002542-f7l4ty2j 294 18 its -PRON- PRP$ cord-002542-f7l4ty2j 294 19 entirety entirety NN cord-002542-f7l4ty2j 294 20 . . . cord-002542-f7l4ty2j 295 1 With with IN cord-002542-f7l4ty2j 295 2 subsequent subsequent JJ cord-002542-f7l4ty2j 295 3 passages passage NNS cord-002542-f7l4ty2j 295 4 , , , cord-002542-f7l4ty2j 295 5 the the DT cord-002542-f7l4ty2j 295 6 number number NN cord-002542-f7l4ty2j 295 7 of of IN cord-002542-f7l4ty2j 295 8 reads read NNS cord-002542-f7l4ty2j 295 9 containing contain VBG cord-002542-f7l4ty2j 295 10 deletions deletion NNS cord-002542-f7l4ty2j 295 11 increases increase NNS cord-002542-f7l4ty2j 295 12 , , , cord-002542-f7l4ty2j 295 13 reaching reach VBG cord-002542-f7l4ty2j 295 14 a a DT cord-002542-f7l4ty2j 295 15 plateau plateau NN cord-002542-f7l4ty2j 295 16 at at IN cord-002542-f7l4ty2j 295 17 passage passage NN cord-002542-f7l4ty2j 295 18 8 8 CD cord-002542-f7l4ty2j 295 19 with with IN cord-002542-f7l4ty2j 295 20 76.0 76.0 CD cord-002542-f7l4ty2j 295 21 % % NN cord-002542-f7l4ty2j 295 22 of of IN cord-002542-f7l4ty2j 295 23 the the DT cord-002542-f7l4ty2j 295 24 reads read NNS cord-002542-f7l4ty2j 295 25 containing contain VBG cord-002542-f7l4ty2j 295 26 two two CD cord-002542-f7l4ty2j 295 27 deletions deletion NNS cord-002542-f7l4ty2j 295 28 and and CC cord-002542-f7l4ty2j 295 29 8.2 8.2 CD cord-002542-f7l4ty2j 295 30 % % NN cord-002542-f7l4ty2j 295 31 containing contain VBG cord-002542-f7l4ty2j 295 32 three three CD cord-002542-f7l4ty2j 295 33 deletions deletion NNS cord-002542-f7l4ty2j 295 34 . . . cord-002542-f7l4ty2j 296 1 DI DI NNP cord-002542-f7l4ty2j 296 2 - - HYPH cord-002542-f7l4ty2j 296 3 RNAs RNAs NNPS cord-002542-f7l4ty2j 296 4 ( ( -LRB- cord-002542-f7l4ty2j 296 5 e.g. e.g. RB cord-002542-f7l4ty2j 296 6 1_317 1_317 CD cord-002542-f7l4ty2j 296 7 ^ ^ NFP cord-002542-f7l4ty2j 296 8 1091 1091 CD cord-002542-f7l4ty2j 296 9 _ _ NN cord-002542-f7l4ty2j 296 10 1242 1242 CD cord-002542-f7l4ty2j 296 11 ^ ^ : cord-002542-f7l4ty2j 296 12 2301_3107 2301_3107 CD cord-002542-f7l4ty2j 296 13 ) ) -RRB- cord-002542-f7l4ty2j 296 14 are be VBP cord-002542-f7l4ty2j 296 15 easily easily RB cord-002542-f7l4ty2j 296 16 identifiable identifiable JJ cord-002542-f7l4ty2j 296 17 as as RB cord-002542-f7l4ty2j 296 18 early early RB cord-002542-f7l4ty2j 296 19 as as IN cord-002542-f7l4ty2j 296 20 passage passage NN cord-002542-f7l4ty2j 296 21 2 2 CD cord-002542-f7l4ty2j 296 22 ( ( -LRB- cord-002542-f7l4ty2j 296 23 S2 S2 NNP cord-002542-f7l4ty2j 296 24 Datafile Datafile NNP cord-002542-f7l4ty2j 296 25 ) ) -RRB- cord-002542-f7l4ty2j 296 26 and and CC cord-002542-f7l4ty2j 296 27 match match VB cord-002542-f7l4ty2j 296 28 well well RB cord-002542-f7l4ty2j 296 29 with with IN cord-002542-f7l4ty2j 296 30 The the DT cord-002542-f7l4ty2j 296 31 number number NN cord-002542-f7l4ty2j 296 32 of of IN cord-002542-f7l4ty2j 296 33 demultiplexed demultiplexed NNP cord-002542-f7l4ty2j 296 34 nanopore nanopore NNP cord-002542-f7l4ty2j 297 1 reads read VBZ cord-002542-f7l4ty2j 297 2 passing pass VBG cord-002542-f7l4ty2j 297 3 quality quality NN cord-002542-f7l4ty2j 297 4 filters filter NNS cord-002542-f7l4ty2j 297 5 are be VBP cord-002542-f7l4ty2j 297 6 shown show VBN cord-002542-f7l4ty2j 297 7 for for IN cord-002542-f7l4ty2j 297 8 each each DT cord-002542-f7l4ty2j 297 9 sample sample NN cord-002542-f7l4ty2j 297 10 . . . cord-002542-f7l4ty2j 298 1 These these DT cord-002542-f7l4ty2j 298 2 were be VBD cord-002542-f7l4ty2j 298 3 mapped map VBN cord-002542-f7l4ty2j 298 4 end end NN cord-002542-f7l4ty2j 298 5 - - HYPH cord-002542-f7l4ty2j 298 6 to to IN cord-002542-f7l4ty2j 298 7 - - HYPH cord-002542-f7l4ty2j 298 8 end end NN cord-002542-f7l4ty2j 298 9 to to IN cord-002542-f7l4ty2j 298 10 the the DT cord-002542-f7l4ty2j 298 11 FHV FHV NNP cord-002542-f7l4ty2j 298 12 genome genome NN cord-002542-f7l4ty2j 298 13 using use VBG cord-002542-f7l4ty2j 298 14 the the DT cord-002542-f7l4ty2j 298 15 BBMap BBMap NNP cord-002542-f7l4ty2j 298 16 suite suite NN cord-002542-f7l4ty2j 298 17 , , , cord-002542-f7l4ty2j 298 18 allowing allow VBG cord-002542-f7l4ty2j 298 19 for for IN cord-002542-f7l4ty2j 298 20 large large JJ cord-002542-f7l4ty2j 298 21 deletions deletion NNS cord-002542-f7l4ty2j 298 22 and and CC cord-002542-f7l4ty2j 298 23 insertions insertion NNS cord-002542-f7l4ty2j 298 24 , , , cord-002542-f7l4ty2j 298 25 which which WDT cord-002542-f7l4ty2j 298 26 were be VBD cord-002542-f7l4ty2j 298 27 counted count VBN cord-002542-f7l4ty2j 298 28 using use VBG cord-002542-f7l4ty2j 298 29 the the DT cord-002542-f7l4ty2j 298 30 CIGAR cigar NN cord-002542-f7l4ty2j 298 31 string stre VBG cord-002542-f7l4ty2j 298 32 from from IN cord-002542-f7l4ty2j 298 33 the the DT cord-002542-f7l4ty2j 298 34 output output NN cord-002542-f7l4ty2j 298 35 alignment alignment NN cord-002542-f7l4ty2j 298 36 SAM SAM NNP cord-002542-f7l4ty2j 298 37 file file NN cord-002542-f7l4ty2j 298 38 . . . cord-002542-f7l4ty2j 299 1 The the DT cord-002542-f7l4ty2j 299 2 Pearson Pearson NNP cord-002542-f7l4ty2j 299 3 correlation correlation NN cord-002542-f7l4ty2j 299 4 coefficients coefficient NNS cord-002542-f7l4ty2j 299 5 of of IN cord-002542-f7l4ty2j 299 6 these these DT cord-002542-f7l4ty2j 299 7 events event NNS cord-002542-f7l4ty2j 299 8 to to IN cord-002542-f7l4ty2j 299 9 those those DT cord-002542-f7l4ty2j 299 10 found find VBN cord-002542-f7l4ty2j 299 11 using use VBG cord-002542-f7l4ty2j 299 12 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 299 13 were be VBD cord-002542-f7l4ty2j 299 14 also also RB cord-002542-f7l4ty2j 299 15 calculated calculate VBN cord-002542-f7l4ty2j 299 16 . . . cord-002542-f7l4ty2j 300 1 The the DT cord-002542-f7l4ty2j 300 2 number number NN cord-002542-f7l4ty2j 300 3 of of IN cord-002542-f7l4ty2j 300 4 reads read NNS cord-002542-f7l4ty2j 300 5 mapping mapping NN cord-002542-f7l4ty2j 300 6 to to IN cord-002542-f7l4ty2j 300 7 FHV FHV NNP cord-002542-f7l4ty2j 300 8 RNA1 RNA1 NNP cord-002542-f7l4ty2j 300 9 and and CC cord-002542-f7l4ty2j 300 10 FHV FHV NNP cord-002542-f7l4ty2j 300 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 300 12 are be VBP cord-002542-f7l4ty2j 300 13 indicated indicate VBN cord-002542-f7l4ty2j 300 14 along along IN cord-002542-f7l4ty2j 300 15 with with IN cord-002542-f7l4ty2j 300 16 the the DT cord-002542-f7l4ty2j 300 17 number number NN cord-002542-f7l4ty2j 300 18 that that WDT cord-002542-f7l4ty2j 300 19 contain contain VBP cord-002542-f7l4ty2j 300 20 0 0 CD cord-002542-f7l4ty2j 300 21 - - SYM cord-002542-f7l4ty2j 300 22 5 5 CD cord-002542-f7l4ty2j 300 23 or or CC cord-002542-f7l4ty2j 300 24 more more JJR cord-002542-f7l4ty2j 300 25 deletions deletion NNS cord-002542-f7l4ty2j 300 26 of of IN cord-002542-f7l4ty2j 300 27 at at RB cord-002542-f7l4ty2j 300 28 least least JJS cord-002542-f7l4ty2j 300 29 25 25 CD cord-002542-f7l4ty2j 300 30 nts nt NNS cord-002542-f7l4ty2j 300 31 . . . cord-002542-f7l4ty2j 301 1 Only only RB cord-002542-f7l4ty2j 301 2 a a DT cord-002542-f7l4ty2j 301 3 small small JJ cord-002542-f7l4ty2j 301 4 number number NN cord-002542-f7l4ty2j 301 5 ( ( -LRB- cord-002542-f7l4ty2j 301 6 < < NNP cord-002542-f7l4ty2j 301 7 5 5 CD cord-002542-f7l4ty2j 301 8 % % NN cord-002542-f7l4ty2j 301 9 ) ) -RRB- cord-002542-f7l4ty2j 301 10 remained remain VBD cord-002542-f7l4ty2j 301 11 unmapped unmapped JJ cord-002542-f7l4ty2j 301 12 . . . cord-002542-f7l4ty2j 302 1 https://doi.org/10.1371/journal.ppat.1006365.t003 https://doi.org/10.1371/journal.ppat.1006365.t003 `` cord-002542-f7l4ty2j 302 2 Pathways pathway NNS cord-002542-f7l4ty2j 302 3 of of IN cord-002542-f7l4ty2j 302 4 FHV FHV NNP cord-002542-f7l4ty2j 302 5 defective defective JJ cord-002542-f7l4ty2j 302 6 RNA RNA NNP cord-002542-f7l4ty2j 302 7 evolution evolution NN cord-002542-f7l4ty2j 302 8 by by IN cord-002542-f7l4ty2j 302 9 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 302 10 and and CC cord-002542-f7l4ty2j 302 11 the the DT cord-002542-f7l4ty2j 302 12 MinION minion XX cord-002542-f7l4ty2j 303 1 the the DT cord-002542-f7l4ty2j 303 2 expected expect VBN cord-002542-f7l4ty2j 303 3 identities identity NNS cord-002542-f7l4ty2j 303 4 based base VBN cord-002542-f7l4ty2j 303 5 on on IN cord-002542-f7l4ty2j 303 6 our -PRON- PRP$ cord-002542-f7l4ty2j 303 7 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 303 8 results result NNS cord-002542-f7l4ty2j 303 9 and and CC cord-002542-f7l4ty2j 303 10 previous previous JJ cord-002542-f7l4ty2j 303 11 studies study NNS cord-002542-f7l4ty2j 303 12 [ [ -LRB- cord-002542-f7l4ty2j 303 13 8 8 CD cord-002542-f7l4ty2j 303 14 , , , cord-002542-f7l4ty2j 303 15 31 31 CD cord-002542-f7l4ty2j 303 16 ] ] -RRB- cord-002542-f7l4ty2j 303 17 . . . cord-002542-f7l4ty2j 304 1 By by IN cord-002542-f7l4ty2j 304 2 the the DT cord-002542-f7l4ty2j 304 3 final final JJ cord-002542-f7l4ty2j 304 4 passages passage NNS cord-002542-f7l4ty2j 304 5 these these DT cord-002542-f7l4ty2j 304 6 species specie NNS cord-002542-f7l4ty2j 304 7 predominate predominate VBP cord-002542-f7l4ty2j 304 8 , , , cord-002542-f7l4ty2j 304 9 leaving leave VBG cord-002542-f7l4ty2j 304 10 only only RB cord-002542-f7l4ty2j 304 11 a a DT cord-002542-f7l4ty2j 304 12 small small JJ cord-002542-f7l4ty2j 304 13 percentage percentage NN cord-002542-f7l4ty2j 304 14 of of IN cord-002542-f7l4ty2j 304 15 full full JJ cord-002542-f7l4ty2j 304 16 - - HYPH cord-002542-f7l4ty2j 304 17 length length NN cord-002542-f7l4ty2j 304 18 wild wild JJ cord-002542-f7l4ty2j 304 19 - - HYPH cord-002542-f7l4ty2j 304 20 type type NN cord-002542-f7l4ty2j 304 21 viral viral JJ cord-002542-f7l4ty2j 304 22 RNAs rna NNS cord-002542-f7l4ty2j 304 23 . . . cord-002542-f7l4ty2j 305 1 While while IN cord-002542-f7l4ty2j 305 2 we -PRON- PRP cord-002542-f7l4ty2j 305 3 can can MD cord-002542-f7l4ty2j 305 4 readily readily RB cord-002542-f7l4ty2j 305 5 identify identify VB cord-002542-f7l4ty2j 305 6 mature mature JJ cord-002542-f7l4ty2j 305 7 DI DI NNP cord-002542-f7l4ty2j 305 8 - - HYPH cord-002542-f7l4ty2j 305 9 RNAs rna NNS cord-002542-f7l4ty2j 305 10 containing contain VBG cord-002542-f7l4ty2j 305 11 two two CD cord-002542-f7l4ty2j 305 12 or or CC cord-002542-f7l4ty2j 305 13 more more JJR cord-002542-f7l4ty2j 305 14 deletions deletion NNS cord-002542-f7l4ty2j 305 15 , , , cord-002542-f7l4ty2j 305 16 few few JJ cord-002542-f7l4ty2j 305 17 single single JJ cord-002542-f7l4ty2j 305 18 - - HYPH cord-002542-f7l4ty2j 305 19 reads read NNS cord-002542-f7l4ty2j 305 20 contain contain VBP cord-002542-f7l4ty2j 305 21 just just RB cord-002542-f7l4ty2j 305 22 one one CD cord-002542-f7l4ty2j 305 23 deletion deletion NN cord-002542-f7l4ty2j 305 24 ( ( -LRB- cord-002542-f7l4ty2j 305 25 < < NNP cord-002542-f7l4ty2j 305 26 6 6 CD cord-002542-f7l4ty2j 305 27 % % NN cord-002542-f7l4ty2j 305 28 ) ) -RRB- cord-002542-f7l4ty2j 305 29 in in IN cord-002542-f7l4ty2j 305 30 all all DT cord-002542-f7l4ty2j 305 31 of of IN cord-002542-f7l4ty2j 305 32 the the DT cord-002542-f7l4ty2j 305 33 passages passage NNS cord-002542-f7l4ty2j 305 34 . . . cord-002542-f7l4ty2j 306 1 Moreover moreover RB cord-002542-f7l4ty2j 306 2 , , , cord-002542-f7l4ty2j 306 3 individual individual JJ cord-002542-f7l4ty2j 306 4 species specie NNS cord-002542-f7l4ty2j 306 5 are be VBP cord-002542-f7l4ty2j 306 6 rarely rarely RB cord-002542-f7l4ty2j 306 7 observed observe VBN cord-002542-f7l4ty2j 306 8 again again RB cord-002542-f7l4ty2j 306 9 in in IN cord-002542-f7l4ty2j 306 10 subsequent subsequent JJ cord-002542-f7l4ty2j 306 11 passages passage NNS cord-002542-f7l4ty2j 306 12 ( ( -LRB- cord-002542-f7l4ty2j 306 13 S6 S6 NNP cord-002542-f7l4ty2j 306 14 Fig Fig NNP cord-002542-f7l4ty2j 306 15 and and CC cord-002542-f7l4ty2j 306 16 S2 S2 NNP cord-002542-f7l4ty2j 306 17 Datafile Datafile NNP cord-002542-f7l4ty2j 306 18 ) ) -RRB- cord-002542-f7l4ty2j 306 19 . . . cord-002542-f7l4ty2j 307 1 Importantly importantly RB cord-002542-f7l4ty2j 307 2 , , , cord-002542-f7l4ty2j 307 3 most most JJS cord-002542-f7l4ty2j 307 4 of of IN cord-002542-f7l4ty2j 307 5 these these DT cord-002542-f7l4ty2j 307 6 single single JJ cord-002542-f7l4ty2j 307 7 events event NNS cord-002542-f7l4ty2j 307 8 do do VBP cord-002542-f7l4ty2j 307 9 not not RB cord-002542-f7l4ty2j 307 10 delete delete VB cord-002542-f7l4ty2j 307 11 the the DT cord-002542-f7l4ty2j 307 12 expected expect VBN cord-002542-f7l4ty2j 307 13 regions region NNS cord-002542-f7l4ty2j 307 14 common common JJ cord-002542-f7l4ty2j 307 15 to to IN cord-002542-f7l4ty2j 307 16 FHV FHV NNP cord-002542-f7l4ty2j 307 17 DI DI NNP cord-002542-f7l4ty2j 307 18 - - HYPH cord-002542-f7l4ty2j 307 19 RNAs rna NNS cord-002542-f7l4ty2j 307 20 . . . cord-002542-f7l4ty2j 308 1 Therefore therefore RB cord-002542-f7l4ty2j 308 2 , , , cord-002542-f7l4ty2j 308 3 they -PRON- PRP cord-002542-f7l4ty2j 308 4 may may MD cord-002542-f7l4ty2j 308 5 either either RB cord-002542-f7l4ty2j 308 6 correspond correspond VB cord-002542-f7l4ty2j 308 7 to to IN cord-002542-f7l4ty2j 308 8 sequencing sequencing NN cord-002542-f7l4ty2j 308 9 artifacts artifact NNS cord-002542-f7l4ty2j 308 10 , , , cord-002542-f7l4ty2j 308 11 or or CC cord-002542-f7l4ty2j 308 12 transient transient JJ cord-002542-f7l4ty2j 308 13 defective defective JJ cord-002542-f7l4ty2j 308 14 RNA RNA NNP cord-002542-f7l4ty2j 308 15 species specie NNS cord-002542-f7l4ty2j 308 16 generated generate VBN cord-002542-f7l4ty2j 308 17 due due IN cord-002542-f7l4ty2j 308 18 to to IN cord-002542-f7l4ty2j 308 19 stochastic stochastic JJ cord-002542-f7l4ty2j 308 20 RNA RNA NNP cord-002542-f7l4ty2j 308 21 recombination recombination NN cord-002542-f7l4ty2j 308 22 , , , cord-002542-f7l4ty2j 308 23 similar similar JJ cord-002542-f7l4ty2j 308 24 to to IN cord-002542-f7l4ty2j 308 25 the the DT cord-002542-f7l4ty2j 308 26 low low JJ cord-002542-f7l4ty2j 308 27 - - HYPH cord-002542-f7l4ty2j 308 28 frequency frequency NN cord-002542-f7l4ty2j 308 29 events event NNS cord-002542-f7l4ty2j 308 30 observed observe VBN cord-002542-f7l4ty2j 308 31 in in IN cord-002542-f7l4ty2j 308 32 the the DT cord-002542-f7l4ty2j 308 33 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 308 34 datasets dataset NNS cord-002542-f7l4ty2j 308 35 . . . cord-002542-f7l4ty2j 309 1 In in IN cord-002542-f7l4ty2j 309 2 later later JJ cord-002542-f7l4ty2j 309 3 passages passage NNS cord-002542-f7l4ty2j 309 4 ( ( -LRB- cord-002542-f7l4ty2j 309 5 beginning begin VBG cord-002542-f7l4ty2j 309 6 at at IN cord-002542-f7l4ty2j 309 7 passage passage NN cord-002542-f7l4ty2j 309 8 3 3 CD cord-002542-f7l4ty2j 309 9 ) ) -RRB- cord-002542-f7l4ty2j 309 10 , , , cord-002542-f7l4ty2j 309 11 we -PRON- PRP cord-002542-f7l4ty2j 309 12 do do VBP cord-002542-f7l4ty2j 309 13 begin begin VB cord-002542-f7l4ty2j 309 14 to to TO cord-002542-f7l4ty2j 309 15 see see VB cord-002542-f7l4ty2j 309 16 the the DT cord-002542-f7l4ty2j 309 17 presumptive presumptive JJ cord-002542-f7l4ty2j 309 18 intermediates intermediate NNS cord-002542-f7l4ty2j 309 19 ( ( -LRB- cord-002542-f7l4ty2j 310 1 e.g. e.g. RB cord-002542-f7l4ty2j 310 2 1_317 1_317 CD cord-002542-f7l4ty2j 310 3 ^ ^ : cord-002542-f7l4ty2j 310 4 1091_3107 1091_3107 CD cord-002542-f7l4ty2j 310 5 or or CC cord-002542-f7l4ty2j 310 6 1_1242 1_1242 CD cord-002542-f7l4ty2j 310 7 ^ ^ NFP cord-002542-f7l4ty2j 310 8 2301_3107 2301_3107 CD cord-002542-f7l4ty2j 310 9 ) ) -RRB- cord-002542-f7l4ty2j 310 10 of of IN cord-002542-f7l4ty2j 310 11 mature mature JJ cord-002542-f7l4ty2j 310 12 DI DI NNP cord-002542-f7l4ty2j 310 13 - - HYPH cord-002542-f7l4ty2j 310 14 RNAs RNAs NNPS cord-002542-f7l4ty2j 310 15 ( ( -LRB- cord-002542-f7l4ty2j 310 16 e.g. e.g. RB cord-002542-f7l4ty2j 310 17 1_317 1_317 CD cord-002542-f7l4ty2j 310 18 ^ ^ : cord-002542-f7l4ty2j 310 19 1091_1242 1091_1242 CD cord-002542-f7l4ty2j 310 20 ^ ^ : cord-002542-f7l4ty2j 310 21 2301_3107 2301_3107 CD cord-002542-f7l4ty2j 310 22 ) ) -RRB- cord-002542-f7l4ty2j 310 23 . . . cord-002542-f7l4ty2j 311 1 However however RB cord-002542-f7l4ty2j 311 2 , , , cord-002542-f7l4ty2j 311 3 this this DT cord-002542-f7l4ty2j 311 4 is be VBZ cord-002542-f7l4ty2j 311 5 after after IN cord-002542-f7l4ty2j 311 6 the the DT cord-002542-f7l4ty2j 311 7 mature mature JJ cord-002542-f7l4ty2j 311 8 DI DI NNP cord-002542-f7l4ty2j 311 9 - - HYPH cord-002542-f7l4ty2j 311 10 RNAs rna NNS cord-002542-f7l4ty2j 311 11 were be VBD cord-002542-f7l4ty2j 311 12 first first RB cord-002542-f7l4ty2j 311 13 observed observe VBN cord-002542-f7l4ty2j 311 14 , , , cord-002542-f7l4ty2j 311 15 and and CC cord-002542-f7l4ty2j 311 16 after after IN cord-002542-f7l4ty2j 311 17 the the DT cord-002542-f7l4ty2j 311 18 point point NN cord-002542-f7l4ty2j 311 19 at at IN cord-002542-f7l4ty2j 311 20 which which WDT cord-002542-f7l4ty2j 311 21 DI DI NNP cord-002542-f7l4ty2j 311 22 - - HYPH cord-002542-f7l4ty2j 311 23 RNAs rna NNS cord-002542-f7l4ty2j 311 24 have have VBP cord-002542-f7l4ty2j 311 25 begun begin VBN cord-002542-f7l4ty2j 311 26 to to TO cord-002542-f7l4ty2j 311 27 accumulate accumulate VB cord-002542-f7l4ty2j 311 28 . . . cord-002542-f7l4ty2j 312 1 Indeed indeed RB cord-002542-f7l4ty2j 312 2 , , , cord-002542-f7l4ty2j 312 3 in in IN cord-002542-f7l4ty2j 312 4 passages passage NNS cord-002542-f7l4ty2j 312 5 2 2 CD cord-002542-f7l4ty2j 312 6 and and CC cord-002542-f7l4ty2j 312 7 3 3 CD cord-002542-f7l4ty2j 312 8 respectively respectively RB cord-002542-f7l4ty2j 312 9 , , , cord-002542-f7l4ty2j 312 10 mature mature JJ cord-002542-f7l4ty2j 312 11 DI DI NNP cord-002542-f7l4ty2j 312 12 - - HYPH cord-002542-f7l4ty2j 312 13 RNAs rna NNS cord-002542-f7l4ty2j 312 14 make make VBP cord-002542-f7l4ty2j 312 15 up up RP cord-002542-f7l4ty2j 312 16 1 1 CD cord-002542-f7l4ty2j 312 17 % % NN cord-002542-f7l4ty2j 312 18 and and CC cord-002542-f7l4ty2j 312 19 30 30 CD cord-002542-f7l4ty2j 312 20 % % NN cord-002542-f7l4ty2j 312 21 of of IN cord-002542-f7l4ty2j 312 22 the the DT cord-002542-f7l4ty2j 312 23 viral viral JJ cord-002542-f7l4ty2j 312 24 population population NN cord-002542-f7l4ty2j 312 25 while while IN cord-002542-f7l4ty2j 312 26 the the DT cord-002542-f7l4ty2j 312 27 singly singly RB cord-002542-f7l4ty2j 312 28 - - HYPH cord-002542-f7l4ty2j 312 29 deleted delete VBN cord-002542-f7l4ty2j 312 30 intermediates intermediate NNS cord-002542-f7l4ty2j 312 31 make make VBP cord-002542-f7l4ty2j 312 32 up up RP cord-002542-f7l4ty2j 312 33 0 0 CD cord-002542-f7l4ty2j 312 34 % % NN cord-002542-f7l4ty2j 312 35 ( ( -LRB- cord-002542-f7l4ty2j 312 36 unobserved unobserved JJ cord-002542-f7l4ty2j 312 37 ) ) -RRB- cord-002542-f7l4ty2j 312 38 and and CC cord-002542-f7l4ty2j 312 39 3 3 CD cord-002542-f7l4ty2j 312 40 % % NN cord-002542-f7l4ty2j 312 41 . . . cord-002542-f7l4ty2j 313 1 Together together RB cord-002542-f7l4ty2j 313 2 with with IN cord-002542-f7l4ty2j 313 3 the the DT cord-002542-f7l4ty2j 313 4 observation observation NN cord-002542-f7l4ty2j 313 5 of of IN cord-002542-f7l4ty2j 313 6 rare rare JJ cord-002542-f7l4ty2j 313 7 DI DI NNP cord-002542-f7l4ty2j 313 8 - - HYPH cord-002542-f7l4ty2j 313 9 RNAs rna NNS cord-002542-f7l4ty2j 313 10 in in IN cord-002542-f7l4ty2j 313 11 the the DT cord-002542-f7l4ty2j 313 12 inoculum inoculum NN cord-002542-f7l4ty2j 313 13 with with IN cord-002542-f7l4ty2j 313 14 the the DT cord-002542-f7l4ty2j 313 15 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 313 16 recombination recombination NN cord-002542-f7l4ty2j 313 17 analysis analysis NN cord-002542-f7l4ty2j 313 18 , , , cord-002542-f7l4ty2j 313 19 these these DT cord-002542-f7l4ty2j 313 20 data datum NNS cord-002542-f7l4ty2j 313 21 indicate indicate VBP cord-002542-f7l4ty2j 313 22 that that IN cord-002542-f7l4ty2j 313 23 single single JJ cord-002542-f7l4ty2j 313 24 - - HYPH cord-002542-f7l4ty2j 313 25 deletion deletion NN cord-002542-f7l4ty2j 313 26 species specie NNS cord-002542-f7l4ty2j 313 27 do do VBP cord-002542-f7l4ty2j 313 28 occur occur VB cord-002542-f7l4ty2j 313 29 early early RB cord-002542-f7l4ty2j 313 30 during during IN cord-002542-f7l4ty2j 313 31 passaging passaging NN cord-002542-f7l4ty2j 313 32 , , , cord-002542-f7l4ty2j 313 33 but but CC cord-002542-f7l4ty2j 313 34 remain remain VBP cord-002542-f7l4ty2j 313 35 poorly poorly RB cord-002542-f7l4ty2j 313 36 abundant abundant JJ cord-002542-f7l4ty2j 313 37 and and CC cord-002542-f7l4ty2j 313 38 do do VBP cord-002542-f7l4ty2j 313 39 not not RB cord-002542-f7l4ty2j 313 40 accumulate accumulate VB cord-002542-f7l4ty2j 313 41 . . . cord-002542-f7l4ty2j 314 1 In in IN cord-002542-f7l4ty2j 314 2 contrast contrast NN cord-002542-f7l4ty2j 314 3 , , , cord-002542-f7l4ty2j 314 4 mature mature JJ cord-002542-f7l4ty2j 314 5 DI DI NNP cord-002542-f7l4ty2j 314 6 - - HYPH cord-002542-f7l4ty2j 314 7 RNAs rna NNS cord-002542-f7l4ty2j 314 8 are be VBP cord-002542-f7l4ty2j 314 9 observed observe VBN cord-002542-f7l4ty2j 314 10 to to TO cord-002542-f7l4ty2j 314 11 rapidly rapidly RB cord-002542-f7l4ty2j 314 12 accumulate accumulate VB cord-002542-f7l4ty2j 314 13 between between IN cord-002542-f7l4ty2j 314 14 passages passage NNS cord-002542-f7l4ty2j 314 15 , , , cord-002542-f7l4ty2j 314 16 indicating indicate VBG cord-002542-f7l4ty2j 314 17 that that IN cord-002542-f7l4ty2j 314 18 they -PRON- PRP cord-002542-f7l4ty2j 314 19 possess possess VBP cord-002542-f7l4ty2j 314 20 a a DT cord-002542-f7l4ty2j 314 21 replicative replicative JJ cord-002542-f7l4ty2j 314 22 advantage advantage NN cord-002542-f7l4ty2j 314 23 above above IN cord-002542-f7l4ty2j 314 24 both both DT cord-002542-f7l4ty2j 314 25 wild wild JJ cord-002542-f7l4ty2j 314 26 - - HYPH cord-002542-f7l4ty2j 314 27 type type NN cord-002542-f7l4ty2j 314 28 viral viral JJ cord-002542-f7l4ty2j 314 29 genomes genome NNS cord-002542-f7l4ty2j 314 30 and and CC cord-002542-f7l4ty2j 314 31 intermediate intermediate JJ cord-002542-f7l4ty2j 314 32 defective defective JJ cord-002542-f7l4ty2j 314 33 RNA RNA NNP cord-002542-f7l4ty2j 314 34 species specie NNS cord-002542-f7l4ty2j 314 35 . . . cord-002542-f7l4ty2j 315 1 In in IN cord-002542-f7l4ty2j 315 2 addition addition NN cord-002542-f7l4ty2j 315 3 to to IN cord-002542-f7l4ty2j 315 4 deletions deletion NNS cord-002542-f7l4ty2j 315 5 , , , cord-002542-f7l4ty2j 315 6 a a DT cord-002542-f7l4ty2j 315 7 small small JJ cord-002542-f7l4ty2j 315 8 number number NN cord-002542-f7l4ty2j 315 9 of of IN cord-002542-f7l4ty2j 315 10 defective defective JJ cord-002542-f7l4ty2j 315 11 RNAs rna NNS cord-002542-f7l4ty2j 315 12 first first RB cord-002542-f7l4ty2j 315 13 appearing appear VBG cord-002542-f7l4ty2j 315 14 at at IN cord-002542-f7l4ty2j 315 15 passage passage NN cord-002542-f7l4ty2j 315 16 5 5 CD cord-002542-f7l4ty2j 315 17 contained contain VBN cord-002542-f7l4ty2j 315 18 insertions insertion NNS cord-002542-f7l4ty2j 315 19 . . . cord-002542-f7l4ty2j 316 1 Interestingly interestingly RB cord-002542-f7l4ty2j 316 2 , , , cord-002542-f7l4ty2j 316 3 the the DT cord-002542-f7l4ty2j 316 4 majority majority NN cord-002542-f7l4ty2j 316 5 of of IN cord-002542-f7l4ty2j 316 6 these these DT cord-002542-f7l4ty2j 316 7 comprised comprise VBN cord-002542-f7l4ty2j 316 8 short short JJ cord-002542-f7l4ty2j 316 9 insertions insertion NNS cord-002542-f7l4ty2j 316 10 of~200 of~200 DT cord-002542-f7l4ty2j 316 11 nucleotides nucleotide NNS cord-002542-f7l4ty2j 316 12 that that WDT cord-002542-f7l4ty2j 316 13 were be VBD cord-002542-f7l4ty2j 316 14 found find VBN cord-002542-f7l4ty2j 316 15 in in IN cord-002542-f7l4ty2j 316 16 first first JJ cord-002542-f7l4ty2j 316 17 300nts 300nts CD cord-002542-f7l4ty2j 316 18 of of IN cord-002542-f7l4ty2j 316 19 the the DT cord-002542-f7l4ty2j 316 20 MinION minion XX cord-002542-f7l4ty2j 316 21 reads read NNS cord-002542-f7l4ty2j 316 22 and and CC cord-002542-f7l4ty2j 316 23 were be VBD cord-002542-f7l4ty2j 316 24 mapped map VBN cord-002542-f7l4ty2j 316 25 between between IN cord-002542-f7l4ty2j 316 26 nts nts NNPS cord-002542-f7l4ty2j 316 27 19 19 CD cord-002542-f7l4ty2j 316 28 and and CC cord-002542-f7l4ty2j 316 29 20 20 CD cord-002542-f7l4ty2j 316 30 of of IN cord-002542-f7l4ty2j 316 31 RNA1 RNA1 NNP cord-002542-f7l4ty2j 316 32 . . . cord-002542-f7l4ty2j 317 1 In in IN cord-002542-f7l4ty2j 317 2 each each DT cord-002542-f7l4ty2j 317 3 case case NN cord-002542-f7l4ty2j 317 4 , , , cord-002542-f7l4ty2j 317 5 these these DT cord-002542-f7l4ty2j 317 6 inserts insert NNS cord-002542-f7l4ty2j 317 7 corresponded correspond VBD cord-002542-f7l4ty2j 317 8 to to IN cord-002542-f7l4ty2j 317 9 nts nt NNS cord-002542-f7l4ty2j 317 10 2300 2300 CD cord-002542-f7l4ty2j 317 11 - - HYPH cord-002542-f7l4ty2j 317 12 2513 2513 CD cord-002542-f7l4ty2j 317 13 of of IN cord-002542-f7l4ty2j 317 14 RNA1 RNA1 NNP cord-002542-f7l4ty2j 317 15 . . . cord-002542-f7l4ty2j 318 1 This this DT cord-002542-f7l4ty2j 318 2 region region NN cord-002542-f7l4ty2j 318 3 corresponds correspond VBZ cord-002542-f7l4ty2j 318 4 to to IN cord-002542-f7l4ty2j 318 5 an an DT cord-002542-f7l4ty2j 318 6 internal internal JJ cord-002542-f7l4ty2j 318 7 response response NN cord-002542-f7l4ty2j 318 8 element element NN cord-002542-f7l4ty2j 318 9 ( ( -LRB- cord-002542-f7l4ty2j 318 10 intRE intRE NNP cord-002542-f7l4ty2j 318 11 ) ) -RRB- cord-002542-f7l4ty2j 318 12 of of IN cord-002542-f7l4ty2j 318 13 the the DT cord-002542-f7l4ty2j 318 14 Proximal Proximal NNP cord-002542-f7l4ty2j 318 15 Sub Sub NNP cord-002542-f7l4ty2j 318 16 - - HYPH cord-002542-f7l4ty2j 318 17 genomic genomic JJ cord-002542-f7l4ty2j 318 18 RNA RNA NNP cord-002542-f7l4ty2j 318 19 Control Control NNP cord-002542-f7l4ty2j 318 20 Element Element NNP cord-002542-f7l4ty2j 318 21 ( ( -LRB- cord-002542-f7l4ty2j 318 22 PSCE PSCE NNP cord-002542-f7l4ty2j 318 23 ) ) -RRB- cord-002542-f7l4ty2j 318 24 previously previously RB cord-002542-f7l4ty2j 318 25 identified identify VBN cord-002542-f7l4ty2j 318 26 as as IN cord-002542-f7l4ty2j 318 27 being be VBG cord-002542-f7l4ty2j 318 28 essential essential JJ cord-002542-f7l4ty2j 318 29 for for IN cord-002542-f7l4ty2j 318 30 FHV FHV NNP cord-002542-f7l4ty2j 318 31 RNA RNA NNP cord-002542-f7l4ty2j 318 32 replication replication NN cord-002542-f7l4ty2j 318 33 and and CC cord-002542-f7l4ty2j 318 34 conserved conserve VBN cord-002542-f7l4ty2j 318 35 in in IN cord-002542-f7l4ty2j 318 36 DI DI NNP cord-002542-f7l4ty2j 318 37 - - HYPH cord-002542-f7l4ty2j 318 38 RNAs rna NNS cord-002542-f7l4ty2j 318 39 species specie NNS cord-002542-f7l4ty2j 318 40 [ [ -LRB- cord-002542-f7l4ty2j 318 41 60 60 CD cord-002542-f7l4ty2j 318 42 ] ] -RRB- cord-002542-f7l4ty2j 318 43 . . . cord-002542-f7l4ty2j 319 1 The the DT cord-002542-f7l4ty2j 319 2 most most RBS cord-002542-f7l4ty2j 319 3 common common JJ cord-002542-f7l4ty2j 319 4 deletion deletion NN cord-002542-f7l4ty2j 319 5 in in IN cord-002542-f7l4ty2j 319 6 the the DT cord-002542-f7l4ty2j 319 7 DI DI NNP cord-002542-f7l4ty2j 319 8 - - HYPH cord-002542-f7l4ty2j 319 9 RNAs rna NNS cord-002542-f7l4ty2j 319 10 in in IN cord-002542-f7l4ty2j 319 11 this this DT cord-002542-f7l4ty2j 319 12 region region NN cord-002542-f7l4ty2j 319 13 of of IN cord-002542-f7l4ty2j 319 14 RNA1 RNA1 NNP cord-002542-f7l4ty2j 319 15 for for IN cord-002542-f7l4ty2j 319 16 the the DT cord-002542-f7l4ty2j 319 17 final final JJ cord-002542-f7l4ty2j 319 18 passages passage NNS cord-002542-f7l4ty2j 319 19 are be VBP cord-002542-f7l4ty2j 319 20 from from IN cord-002542-f7l4ty2j 319 21 1242 1242 CD cord-002542-f7l4ty2j 319 22 to to IN cord-002542-f7l4ty2j 319 23 2301 2301 CD cord-002542-f7l4ty2j 319 24 , , , cord-002542-f7l4ty2j 319 25 which which WDT cord-002542-f7l4ty2j 319 26 retains retain VBZ cord-002542-f7l4ty2j 319 27 the the DT cord-002542-f7l4ty2j 319 28 intRE intRE NNP cord-002542-f7l4ty2j 319 29 . . . cord-002542-f7l4ty2j 320 1 However however RB cord-002542-f7l4ty2j 320 2 , , , cord-002542-f7l4ty2j 320 3 there there EX cord-002542-f7l4ty2j 320 4 are be VBP cord-002542-f7l4ty2j 320 5 also also RB cord-002542-f7l4ty2j 320 6 a a DT cord-002542-f7l4ty2j 320 7 large large JJ cord-002542-f7l4ty2j 320 8 number number NN cord-002542-f7l4ty2j 320 9 of of IN cord-002542-f7l4ty2j 320 10 deletions deletion NNS cord-002542-f7l4ty2j 320 11 ranging range VBG cord-002542-f7l4ty2j 320 12 from from IN cord-002542-f7l4ty2j 320 13 1245 1245 CD cord-002542-f7l4ty2j 320 14 to to IN cord-002542-f7l4ty2j 320 15 2514 2514 CD cord-002542-f7l4ty2j 320 16 , , , cord-002542-f7l4ty2j 320 17 which which WDT cord-002542-f7l4ty2j 320 18 would would MD cord-002542-f7l4ty2j 320 19 delete delete VB cord-002542-f7l4ty2j 320 20 the the DT cord-002542-f7l4ty2j 320 21 essential essential JJ cord-002542-f7l4ty2j 320 22 intRE intRE NNP cord-002542-f7l4ty2j 320 23 . . . cord-002542-f7l4ty2j 321 1 Closer close JJR cord-002542-f7l4ty2j 321 2 inspection inspection NN cord-002542-f7l4ty2j 321 3 of of IN cord-002542-f7l4ty2j 321 4 the the DT cord-002542-f7l4ty2j 321 5 MinION MinION NNP cord-002542-f7l4ty2j 321 6 data datum NNS cord-002542-f7l4ty2j 321 7 reveals reveal VBZ cord-002542-f7l4ty2j 321 8 that that IN cord-002542-f7l4ty2j 321 9 the the DT cord-002542-f7l4ty2j 321 10 majority majority NN cord-002542-f7l4ty2j 321 11 of of IN cord-002542-f7l4ty2j 321 12 these these DT cord-002542-f7l4ty2j 321 13 reads read NNS cord-002542-f7l4ty2j 321 14 ( ( -LRB- cord-002542-f7l4ty2j 321 15 > > NFP cord-002542-f7l4ty2j 321 16 90 90 CD cord-002542-f7l4ty2j 321 17 % % NN cord-002542-f7l4ty2j 321 18 ) ) -RRB- cord-002542-f7l4ty2j 321 19 that that WDT cord-002542-f7l4ty2j 321 20 contain contain VBP cord-002542-f7l4ty2j 321 21 the the DT cord-002542-f7l4ty2j 321 22 200nt 200nt NNP cord-002542-f7l4ty2j 321 23 intRE intre JJ cord-002542-f7l4ty2j 321 24 insertion insertion NN cord-002542-f7l4ty2j 321 25 concomitantly concomitantly RB cord-002542-f7l4ty2j 321 26 contained contain VBD cord-002542-f7l4ty2j 321 27 deletions deletion NNS cord-002542-f7l4ty2j 321 28 from from IN cord-002542-f7l4ty2j 321 29 1245 1245 CD cord-002542-f7l4ty2j 321 30 - - SYM cord-002542-f7l4ty2j 321 31 2514 2514 CD cord-002542-f7l4ty2j 321 32 , , , cord-002542-f7l4ty2j 321 33 indicating indicate VBG cord-002542-f7l4ty2j 321 34 that that IN cord-002542-f7l4ty2j 321 35 these these DT cord-002542-f7l4ty2j 321 36 two two CD cord-002542-f7l4ty2j 321 37 events event NNS cord-002542-f7l4ty2j 321 38 are be VBP cord-002542-f7l4ty2j 321 39 correlated correlate VBN cord-002542-f7l4ty2j 321 40 . . . cord-002542-f7l4ty2j 322 1 The the DT cord-002542-f7l4ty2j 322 2 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 322 3 data datum NNS cord-002542-f7l4ty2j 322 4 also also RB cord-002542-f7l4ty2j 322 5 shows show VBZ cord-002542-f7l4ty2j 322 6 a a DT cord-002542-f7l4ty2j 322 7 frequent frequent JJ cord-002542-f7l4ty2j 322 8 recombination recombination NN cord-002542-f7l4ty2j 322 9 event event NN cord-002542-f7l4ty2j 322 10 , , , cord-002542-f7l4ty2j 322 11 2513 2513 CD cord-002542-f7l4ty2j 322 12 ^ ^ SYM cord-002542-f7l4ty2j 322 13 21 21 CD cord-002542-f7l4ty2j 322 14 , , , cord-002542-f7l4ty2j 322 15 which which WDT cord-002542-f7l4ty2j 322 16 appears appear VBZ cord-002542-f7l4ty2j 322 17 first first RB cord-002542-f7l4ty2j 322 18 in in IN cord-002542-f7l4ty2j 322 19 passage passage NN cord-002542-f7l4ty2j 322 20 4 4 CD cord-002542-f7l4ty2j 322 21 and and CC cord-002542-f7l4ty2j 322 22 is be VBZ cord-002542-f7l4ty2j 322 23 among among IN cord-002542-f7l4ty2j 322 24 the the DT cord-002542-f7l4ty2j 322 25 10 10 CD cord-002542-f7l4ty2j 322 26 most most RBS cord-002542-f7l4ty2j 322 27 common common JJ cord-002542-f7l4ty2j 322 28 events event NNS cord-002542-f7l4ty2j 322 29 in in IN cord-002542-f7l4ty2j 322 30 the the DT cord-002542-f7l4ty2j 322 31 final final JJ cord-002542-f7l4ty2j 322 32 5 5 CD cord-002542-f7l4ty2j 322 33 passages passage NNS cord-002542-f7l4ty2j 322 34 ( ( -LRB- cord-002542-f7l4ty2j 322 35 S1 S1 NNP cord-002542-f7l4ty2j 322 36 Datafile Datafile NNP cord-002542-f7l4ty2j 322 37 ) ) -RRB- cord-002542-f7l4ty2j 322 38 . . . cord-002542-f7l4ty2j 323 1 This this DT cord-002542-f7l4ty2j 323 2 matches match VBZ cord-002542-f7l4ty2j 323 3 precisely precisely RB cord-002542-f7l4ty2j 323 4 the the DT cord-002542-f7l4ty2j 323 5 3 3 CD cord-002542-f7l4ty2j 323 6 ' ' POS cord-002542-f7l4ty2j 323 7 junction junction NN cord-002542-f7l4ty2j 323 8 site site NN cord-002542-f7l4ty2j 323 9 of of IN cord-002542-f7l4ty2j 323 10 the the DT cord-002542-f7l4ty2j 323 11 insertion insertion NN cord-002542-f7l4ty2j 323 12 event event NN cord-002542-f7l4ty2j 323 13 detected detect VBN cord-002542-f7l4ty2j 323 14 in in IN cord-002542-f7l4ty2j 323 15 the the DT cord-002542-f7l4ty2j 323 16 Min Min NNP cord-002542-f7l4ty2j 323 17 - - HYPH cord-002542-f7l4ty2j 323 18 ION ION NNP cord-002542-f7l4ty2j 323 19 data datum NNS cord-002542-f7l4ty2j 323 20 . . . cord-002542-f7l4ty2j 324 1 However however RB cord-002542-f7l4ty2j 324 2 , , , cord-002542-f7l4ty2j 324 3 the the DT cord-002542-f7l4ty2j 324 4 event event NN cord-002542-f7l4ty2j 324 5 20 20 CD cord-002542-f7l4ty2j 324 6 ^ ^ SYM cord-002542-f7l4ty2j 324 7 2300 2300 CD cord-002542-f7l4ty2j 324 8 corresponding correspond VBG cord-002542-f7l4ty2j 324 9 to to IN cord-002542-f7l4ty2j 324 10 the the DT cord-002542-f7l4ty2j 324 11 5 5 CD cord-002542-f7l4ty2j 324 12 ' ' POS cord-002542-f7l4ty2j 324 13 junction junction NN cord-002542-f7l4ty2j 324 14 site site NN cord-002542-f7l4ty2j 324 15 was be VBD cord-002542-f7l4ty2j 324 16 not not RB cord-002542-f7l4ty2j 324 17 detected detect VBN cord-002542-f7l4ty2j 324 18 in in IN cord-002542-f7l4ty2j 324 19 our -PRON- PRP$ cord-002542-f7l4ty2j 324 20 initial initial JJ cord-002542-f7l4ty2j 324 21 ViReMa virema NN cord-002542-f7l4ty2j 324 22 analysis analysis NN cord-002542-f7l4ty2j 324 23 of of IN cord-002542-f7l4ty2j 324 24 the the DT cord-002542-f7l4ty2j 324 25 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 324 26 data datum NNS cord-002542-f7l4ty2j 324 27 as as IN cord-002542-f7l4ty2j 324 28 this this DT cord-002542-f7l4ty2j 324 29 would would MD cord-002542-f7l4ty2j 324 30 have have VB cord-002542-f7l4ty2j 324 31 required require VBN cord-002542-f7l4ty2j 324 32 a a DT cord-002542-f7l4ty2j 324 33 search search NN cord-002542-f7l4ty2j 324 34 seed seed NN cord-002542-f7l4ty2j 324 35 length length NN cord-002542-f7l4ty2j 324 36 of of IN cord-002542-f7l4ty2j 324 37 less less JJR cord-002542-f7l4ty2j 324 38 than than IN cord-002542-f7l4ty2j 324 39 20 20 CD cord-002542-f7l4ty2j 324 40 nts nt NNS cord-002542-f7l4ty2j 324 41 . . . cord-002542-f7l4ty2j 325 1 Repeating repeat VBG cord-002542-f7l4ty2j 325 2 the the DT cord-002542-f7l4ty2j 325 3 ViReMa virema NN cord-002542-f7l4ty2j 325 4 analysis analysis NN cord-002542-f7l4ty2j 325 5 using use VBG cord-002542-f7l4ty2j 325 6 a a DT cord-002542-f7l4ty2j 325 7 seed seed NN cord-002542-f7l4ty2j 325 8 length length NN cord-002542-f7l4ty2j 325 9 of of IN cord-002542-f7l4ty2j 325 10 17 17 CD cord-002542-f7l4ty2j 325 11 does do VBZ cord-002542-f7l4ty2j 325 12 indeed indeed RB cord-002542-f7l4ty2j 325 13 reveal reveal VB cord-002542-f7l4ty2j 325 14 the the DT cord-002542-f7l4ty2j 325 15 presence presence NN cord-002542-f7l4ty2j 325 16 of of IN cord-002542-f7l4ty2j 325 17 the the DT cord-002542-f7l4ty2j 325 18 20 20 CD cord-002542-f7l4ty2j 325 19 ^ ^ SYM cord-002542-f7l4ty2j 325 20 2300 2300 CD cord-002542-f7l4ty2j 325 21 recombination recombination NN cord-002542-f7l4ty2j 325 22 event event NN cord-002542-f7l4ty2j 325 23 . . . cord-002542-f7l4ty2j 326 1 This this DT cord-002542-f7l4ty2j 326 2 event event NN cord-002542-f7l4ty2j 326 3 is be VBZ cord-002542-f7l4ty2j 326 4 rarely rarely RB cord-002542-f7l4ty2j 326 5 observed observe VBN cord-002542-f7l4ty2j 326 6 in in IN cord-002542-f7l4ty2j 326 7 either either DT cord-002542-f7l4ty2j 326 8 of of IN cord-002542-f7l4ty2j 326 9 the the DT cord-002542-f7l4ty2j 326 10 other other JJ cord-002542-f7l4ty2j 326 11 two two CD cord-002542-f7l4ty2j 326 12 replicate replicate VB cord-002542-f7l4ty2j 326 13 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 326 14 data datum NNS cord-002542-f7l4ty2j 326 15 ( ( -LRB- cord-002542-f7l4ty2j 326 16 7 7 CD cord-002542-f7l4ty2j 326 17 and and CC cord-002542-f7l4ty2j 326 18 31 31 CD cord-002542-f7l4ty2j 326 19 total total JJ cord-002542-f7l4ty2j 326 20 reads read NNS cord-002542-f7l4ty2j 326 21 across across IN cord-002542-f7l4ty2j 326 22 all all DT cord-002542-f7l4ty2j 326 23 passages passage NNS cord-002542-f7l4ty2j 326 24 of of IN cord-002542-f7l4ty2j 326 25 replicates replicate NNS cord-002542-f7l4ty2j 326 26 1 1 CD cord-002542-f7l4ty2j 326 27 and and CC cord-002542-f7l4ty2j 326 28 3 3 CD cord-002542-f7l4ty2j 326 29 respectively respectively RB cord-002542-f7l4ty2j 326 30 ) ) -RRB- cord-002542-f7l4ty2j 326 31 . . . cord-002542-f7l4ty2j 327 1 These these DT cord-002542-f7l4ty2j 327 2 data datum NNS cord-002542-f7l4ty2j 327 3 indicate indicate VBP cord-002542-f7l4ty2j 327 4 that that IN cord-002542-f7l4ty2j 327 5 in in IN cord-002542-f7l4ty2j 327 6 a a DT cord-002542-f7l4ty2j 327 7 number number NN cord-002542-f7l4ty2j 327 8 of of IN cord-002542-f7l4ty2j 327 9 defective defective JJ cord-002542-f7l4ty2j 327 10 RNA RNA NNP cord-002542-f7l4ty2j 327 11 genomes genome NNS cord-002542-f7l4ty2j 327 12 , , , cord-002542-f7l4ty2j 327 13 the the DT cord-002542-f7l4ty2j 327 14 intRE intre JJ cord-002542-f7l4ty2j 327 15 element element NN cord-002542-f7l4ty2j 327 16 has have VBZ cord-002542-f7l4ty2j 327 17 been be VBN cord-002542-f7l4ty2j 327 18 deleted delete VBN cord-002542-f7l4ty2j 327 19 and and CC cord-002542-f7l4ty2j 327 20 subsequently subsequently RB cord-002542-f7l4ty2j 327 21 re re VB cord-002542-f7l4ty2j 327 22 - - VBN cord-002542-f7l4ty2j 327 23 inserted insert VBN cord-002542-f7l4ty2j 327 24 at at IN cord-002542-f7l4ty2j 327 25 the the DT cord-002542-f7l4ty2j 327 26 5 5 CD cord-002542-f7l4ty2j 327 27 ' ' NN cord-002542-f7l4ty2j 327 28 end end NN cord-002542-f7l4ty2j 327 29 of of IN cord-002542-f7l4ty2j 327 30 the the DT cord-002542-f7l4ty2j 327 31 defective defective JJ cord-002542-f7l4ty2j 327 32 RNA RNA NNP cord-002542-f7l4ty2j 327 33 genome genome NN cord-002542-f7l4ty2j 327 34 . . . cord-002542-f7l4ty2j 328 1 As as IN cord-002542-f7l4ty2j 328 2 the the DT cord-002542-f7l4ty2j 328 3 intRE intre JJ cord-002542-f7l4ty2j 328 4 element element NN cord-002542-f7l4ty2j 328 5 is be VBZ cord-002542-f7l4ty2j 328 6 required require VBN cord-002542-f7l4ty2j 328 7 for for IN cord-002542-f7l4ty2j 328 8 regulation regulation NN cord-002542-f7l4ty2j 328 9 of of IN cord-002542-f7l4ty2j 328 10 RNA RNA NNP cord-002542-f7l4ty2j 328 11 replication replication NN cord-002542-f7l4ty2j 328 12 , , , cord-002542-f7l4ty2j 328 13 presumably presumably RB cord-002542-f7l4ty2j 328 14 this this DT cord-002542-f7l4ty2j 328 15 maintains maintain VBZ cord-002542-f7l4ty2j 328 16 the the DT cord-002542-f7l4ty2j 328 17 ability ability NN cord-002542-f7l4ty2j 328 18 for for IN cord-002542-f7l4ty2j 328 19 this this DT cord-002542-f7l4ty2j 328 20 highly highly RB cord-002542-f7l4ty2j 328 21 - - HYPH cord-002542-f7l4ty2j 328 22 rearranged rearrange VBN cord-002542-f7l4ty2j 328 23 defective defective JJ cord-002542-f7l4ty2j 328 24 RNA RNA NNP cord-002542-f7l4ty2j 328 25 to to TO cord-002542-f7l4ty2j 328 26 replicate replicate VB cord-002542-f7l4ty2j 328 27 . . . cord-002542-f7l4ty2j 329 1 These these DT cord-002542-f7l4ty2j 329 2 data datum NNS cord-002542-f7l4ty2j 329 3 provide provide VBP cord-002542-f7l4ty2j 329 4 a a DT cord-002542-f7l4ty2j 329 5 comprehensive comprehensive JJ cord-002542-f7l4ty2j 329 6 overview overview NN cord-002542-f7l4ty2j 329 7 of of IN cord-002542-f7l4ty2j 329 8 the the DT cord-002542-f7l4ty2j 329 9 different different JJ cord-002542-f7l4ty2j 329 10 species specie NNS cord-002542-f7l4ty2j 329 11 of of IN cord-002542-f7l4ty2j 329 12 defective defective JJ cord-002542-f7l4ty2j 329 13 RNAs rna NNS cord-002542-f7l4ty2j 329 14 that that WDT cord-002542-f7l4ty2j 329 15 are be VBP cord-002542-f7l4ty2j 329 16 present present JJ cord-002542-f7l4ty2j 329 17 during during IN cord-002542-f7l4ty2j 329 18 viral viral JJ cord-002542-f7l4ty2j 329 19 passaging passaging NN cord-002542-f7l4ty2j 329 20 . . . cord-002542-f7l4ty2j 330 1 Illustrating illustrate VBG cord-002542-f7l4ty2j 330 2 such such PDT cord-002542-f7l4ty2j 330 3 a a DT cord-002542-f7l4ty2j 330 4 complex complex JJ cord-002542-f7l4ty2j 330 5 set set NN cord-002542-f7l4ty2j 330 6 of of IN cord-002542-f7l4ty2j 330 7 data data NN cord-002542-f7l4ty2j 330 8 is be VBZ cord-002542-f7l4ty2j 330 9 a a DT cord-002542-f7l4ty2j 330 10 challenge challenge NN cord-002542-f7l4ty2j 330 11 as as IN cord-002542-f7l4ty2j 330 12 each each DT cord-002542-f7l4ty2j 330 13 sample sample NN cord-002542-f7l4ty2j 330 14 contains contain VBZ cord-002542-f7l4ty2j 330 15 a a DT cord-002542-f7l4ty2j 330 16 large large JJ cord-002542-f7l4ty2j 330 17 number number NN cord-002542-f7l4ty2j 330 18 of of IN cord-002542-f7l4ty2j 330 19 genome genome NN cord-002542-f7l4ty2j 330 20 arrangements arrangement NNS cord-002542-f7l4ty2j 330 21 ( ( -LRB- cord-002542-f7l4ty2j 330 22 6030 6030 CD cord-002542-f7l4ty2j 330 23 and and CC cord-002542-f7l4ty2j 330 24 3639 3639 CD cord-002542-f7l4ty2j 330 25 for for IN cord-002542-f7l4ty2j 330 26 RNA1 RNA1 NNP cord-002542-f7l4ty2j 330 27 and and CC cord-002542-f7l4ty2j 330 28 RNA2 RNA2 NNP cord-002542-f7l4ty2j 330 29 respectively respectively RB cord-002542-f7l4ty2j 330 30 ) ) -RRB- cord-002542-f7l4ty2j 330 31 and and CC cord-002542-f7l4ty2j 330 32 frequencies frequency NNS cord-002542-f7l4ty2j 330 33 of of IN cord-002542-f7l4ty2j 330 34 these these DT cord-002542-f7l4ty2j 330 35 species specie NNS cord-002542-f7l4ty2j 330 36 vary vary VBP cord-002542-f7l4ty2j 330 37 substantially substantially RB cord-002542-f7l4ty2j 330 38 over over IN cord-002542-f7l4ty2j 330 39 time time NN cord-002542-f7l4ty2j 330 40 . . . cord-002542-f7l4ty2j 331 1 We -PRON- PRP cord-002542-f7l4ty2j 331 2 found find VBD cord-002542-f7l4ty2j 331 3 that that IN cord-002542-f7l4ty2j 331 4 illustrating illustrate VBG cord-002542-f7l4ty2j 331 5 these these DT cord-002542-f7l4ty2j 331 6 data datum NNS cord-002542-f7l4ty2j 331 7 as as IN cord-002542-f7l4ty2j 331 8 a a DT cord-002542-f7l4ty2j 331 9 stacked stack VBN cord-002542-f7l4ty2j 331 10 area area NN cord-002542-f7l4ty2j 331 11 plot plot NN cord-002542-f7l4ty2j 331 12 gave give VBD cord-002542-f7l4ty2j 331 13 the the DT cord-002542-f7l4ty2j 331 14 most most RBS cord-002542-f7l4ty2j 331 15 informative informative JJ cord-002542-f7l4ty2j 331 16 summary summary NN cord-002542-f7l4ty2j 331 17 of of IN cord-002542-f7l4ty2j 331 18 the the DT cord-002542-f7l4ty2j 331 19 changes change NNS cord-002542-f7l4ty2j 331 20 of of IN cord-002542-f7l4ty2j 331 21 the the DT cord-002542-f7l4ty2j 331 22 many many JJ cord-002542-f7l4ty2j 331 23 different different JJ cord-002542-f7l4ty2j 331 24 type type NN cord-002542-f7l4ty2j 331 25 of of IN cord-002542-f7l4ty2j 331 26 DI DI NNP cord-002542-f7l4ty2j 331 27 - - HYPH cord-002542-f7l4ty2j 331 28 RNA RNA NNP cord-002542-f7l4ty2j 331 29 species species NN cord-002542-f7l4ty2j 331 30 over over IN cord-002542-f7l4ty2j 331 31 time time NN cord-002542-f7l4ty2j 331 32 . . . cord-002542-f7l4ty2j 332 1 Due due IN cord-002542-f7l4ty2j 332 2 to to IN cord-002542-f7l4ty2j 332 3 the the DT cord-002542-f7l4ty2j 332 4 moderate moderate JJ cord-002542-f7l4ty2j 332 5 errorrate errorrate NN cord-002542-f7l4ty2j 332 6 of of IN cord-002542-f7l4ty2j 332 7 the the DT cord-002542-f7l4ty2j 332 8 nanopore nanopore NNP cord-002542-f7l4ty2j 332 9 read read NNP cord-002542-f7l4ty2j 332 10 data data NNP cord-002542-f7l4ty2j 332 11 , , , cord-002542-f7l4ty2j 332 12 the the DT cord-002542-f7l4ty2j 332 13 exact exact JJ cord-002542-f7l4ty2j 332 14 identification identification NN cord-002542-f7l4ty2j 332 15 of of IN cord-002542-f7l4ty2j 332 16 a a DT cord-002542-f7l4ty2j 332 17 recombination recombination NN cord-002542-f7l4ty2j 332 18 event event NN cord-002542-f7l4ty2j 332 19 and and CC cord-002542-f7l4ty2j 332 20 thus thus RB cord-002542-f7l4ty2j 332 21 annotation annotation NN cord-002542-f7l4ty2j 332 22 of of IN cord-002542-f7l4ty2j 332 23 that that DT cord-002542-f7l4ty2j 332 24 genome genome NN cord-002542-f7l4ty2j 332 25 may may MD cord-002542-f7l4ty2j 332 26 be be VB cord-002542-f7l4ty2j 332 27 incorrect incorrect JJ cord-002542-f7l4ty2j 332 28 . . . cord-002542-f7l4ty2j 333 1 This this DT cord-002542-f7l4ty2j 333 2 would would MD cord-002542-f7l4ty2j 333 3 result result VB cord-002542-f7l4ty2j 333 4 in in IN cord-002542-f7l4ty2j 333 5 an an DT cord-002542-f7l4ty2j 333 6 over over IN cord-002542-f7l4ty2j 333 7 - - HYPH cord-002542-f7l4ty2j 333 8 estimation estimation NN cord-002542-f7l4ty2j 333 9 in in IN cord-002542-f7l4ty2j 333 10 the the DT cord-002542-f7l4ty2j 333 11 potential potential JJ cord-002542-f7l4ty2j 333 12 number number NN cord-002542-f7l4ty2j 333 13 of of IN cord-002542-f7l4ty2j 333 14 unique unique JJ cord-002542-f7l4ty2j 333 15 structural structural JJ cord-002542-f7l4ty2j 333 16 variants variant NNS cord-002542-f7l4ty2j 333 17 . . . cord-002542-f7l4ty2j 334 1 Therefore therefore RB cord-002542-f7l4ty2j 334 2 we -PRON- PRP cord-002542-f7l4ty2j 334 3 filtered filter VBD cord-002542-f7l4ty2j 334 4 datasets dataset NNS cord-002542-f7l4ty2j 334 5 by by IN cord-002542-f7l4ty2j 334 6 requiring require VBG cord-002542-f7l4ty2j 334 7 genomes genome NNS cord-002542-f7l4ty2j 334 8 to to TO cord-002542-f7l4ty2j 334 9 be be VB cord-002542-f7l4ty2j 334 10 represented represent VBN cord-002542-f7l4ty2j 334 11 by by IN cord-002542-f7l4ty2j 334 12 three three CD cord-002542-f7l4ty2j 334 13 or or CC cord-002542-f7l4ty2j 334 14 more more JJR cord-002542-f7l4ty2j 334 15 reads read NNS cord-002542-f7l4ty2j 334 16 . . . cord-002542-f7l4ty2j 335 1 While while IN cord-002542-f7l4ty2j 335 2 removing remove VBG cord-002542-f7l4ty2j 335 3 a a DT cord-002542-f7l4ty2j 335 4 lot lot NN cord-002542-f7l4ty2j 335 5 of of IN cord-002542-f7l4ty2j 335 6 noise noise NN cord-002542-f7l4ty2j 335 7 , , , cord-002542-f7l4ty2j 335 8 this this DT cord-002542-f7l4ty2j 335 9 has have VBZ cord-002542-f7l4ty2j 335 10 the the DT cord-002542-f7l4ty2j 335 11 drawback drawback NN cord-002542-f7l4ty2j 335 12 that that IN cord-002542-f7l4ty2j 335 13 we -PRON- PRP cord-002542-f7l4ty2j 335 14 might may MD cord-002542-f7l4ty2j 335 15 be be VB cord-002542-f7l4ty2j 335 16 losing lose VBG cord-002542-f7l4ty2j 335 17 rare rare JJ cord-002542-f7l4ty2j 335 18 defective defective JJ cord-002542-f7l4ty2j 335 19 RNAs rna NNS cord-002542-f7l4ty2j 335 20 . . . cord-002542-f7l4ty2j 336 1 Stacked stack VBN cord-002542-f7l4ty2j 336 2 area area NN cord-002542-f7l4ty2j 336 3 plots plot NNS cord-002542-f7l4ty2j 336 4 for for IN cord-002542-f7l4ty2j 336 5 genomes genome NNS cord-002542-f7l4ty2j 336 6 represented represent VBN cord-002542-f7l4ty2j 336 7 by by IN cord-002542-f7l4ty2j 336 8 three three CD cord-002542-f7l4ty2j 336 9 or or CC cord-002542-f7l4ty2j 336 10 more more JJR cord-002542-f7l4ty2j 336 11 reads read NNS cord-002542-f7l4ty2j 336 12 are be VBP cord-002542-f7l4ty2j 336 13 shown show VBN cord-002542-f7l4ty2j 336 14 in in IN cord-002542-f7l4ty2j 336 15 The the DT cord-002542-f7l4ty2j 336 16 stacked stack VBN cord-002542-f7l4ty2j 336 17 area area NN cord-002542-f7l4ty2j 336 18 plot plot NN cord-002542-f7l4ty2j 336 19 for for IN cord-002542-f7l4ty2j 336 20 RNA1 RNA1 NNP cord-002542-f7l4ty2j 336 21 ( ( -LRB- cord-002542-f7l4ty2j 336 22 Fig Fig NNP cord-002542-f7l4ty2j 336 23 6A 6a CD cord-002542-f7l4ty2j 336 24 ) ) -RRB- cord-002542-f7l4ty2j 336 25 shows show VBZ cord-002542-f7l4ty2j 336 26 that that IN cord-002542-f7l4ty2j 336 27 the the DT cord-002542-f7l4ty2j 336 28 composition composition NN cord-002542-f7l4ty2j 336 29 of of IN cord-002542-f7l4ty2j 336 30 DI DI NNP cord-002542-f7l4ty2j 336 31 - - HYPH cord-002542-f7l4ty2j 336 32 RNAs rna NNS cord-002542-f7l4ty2j 336 33 in in IN cord-002542-f7l4ty2j 336 34 the the DT cord-002542-f7l4ty2j 336 35 viral viral JJ cord-002542-f7l4ty2j 336 36 population population NN cord-002542-f7l4ty2j 336 37 changes change VBZ cord-002542-f7l4ty2j 336 38 over over IN cord-002542-f7l4ty2j 336 39 time time NN cord-002542-f7l4ty2j 336 40 and and CC cord-002542-f7l4ty2j 336 41 new new JJ cord-002542-f7l4ty2j 336 42 species specie NNS cord-002542-f7l4ty2j 336 43 appear appear VBP cord-002542-f7l4ty2j 336 44 at at IN cord-002542-f7l4ty2j 336 45 each each DT cord-002542-f7l4ty2j 336 46 passage passage NN cord-002542-f7l4ty2j 336 47 . . . cord-002542-f7l4ty2j 337 1 For for IN cord-002542-f7l4ty2j 337 2 example example NN cord-002542-f7l4ty2j 337 3 , , , cord-002542-f7l4ty2j 337 4 the the DT cord-002542-f7l4ty2j 337 5 most most RBS cord-002542-f7l4ty2j 337 6 abundant abundant JJ cord-002542-f7l4ty2j 337 7 defective defective JJ cord-002542-f7l4ty2j 337 8 RNA1 RNA1 NNP cord-002542-f7l4ty2j 337 9 species specie NNS cord-002542-f7l4ty2j 337 10 in in IN cord-002542-f7l4ty2j 337 11 passage passage NN cord-002542-f7l4ty2j 337 12 5 5 CD cord-002542-f7l4ty2j 337 13 is be VBZ cord-002542-f7l4ty2j 337 14 ' ' '' cord-002542-f7l4ty2j 337 15 1_317 1_317 CD cord-002542-f7l4ty2j 337 16 ^ ^ : cord-002542-f7l4ty2j 337 17 1091_1242 1091_1242 CD cord-002542-f7l4ty2j 337 18 ^ ^ : cord-002542-f7l4ty2j 337 19 2301_3107 2301_3107 CD cord-002542-f7l4ty2j 337 20 ' ' '' cord-002542-f7l4ty2j 337 21 but but CC cord-002542-f7l4ty2j 337 22 reduces reduce VBZ cord-002542-f7l4ty2j 337 23 in in IN cord-002542-f7l4ty2j 337 24 relative relative JJ cord-002542-f7l4ty2j 337 25 frequency frequency NN cord-002542-f7l4ty2j 337 26 in in IN cord-002542-f7l4ty2j 337 27 later later JJ cord-002542-f7l4ty2j 337 28 passages passage NNS cord-002542-f7l4ty2j 337 29 . . . cord-002542-f7l4ty2j 338 1 The the DT cord-002542-f7l4ty2j 338 2 most most RBS cord-002542-f7l4ty2j 338 3 abundant abundant JJ cord-002542-f7l4ty2j 338 4 species specie NNS cord-002542-f7l4ty2j 338 5 in in IN cord-002542-f7l4ty2j 338 6 the the DT cord-002542-f7l4ty2j 338 7 final final JJ cord-002542-f7l4ty2j 338 8 passage passage NN cord-002542-f7l4ty2j 338 9 9 9 CD cord-002542-f7l4ty2j 338 10 is be VBZ cord-002542-f7l4ty2j 338 11 ' ' `` cord-002542-f7l4ty2j 338 12 1_313 1_313 CD cord-002542-f7l4ty2j 338 13 ^ ^ NFP cord-002542-f7l4ty2j 338 14 941_1241 941_1241 CD cord-002542-f7l4ty2j 338 15 ^ ^ : cord-002542-f7l4ty2j 338 16 2325_3107 2325_3107 CD cord-002542-f7l4ty2j 338 17 ' ' '' cord-002542-f7l4ty2j 338 18 , , , cord-002542-f7l4ty2j 338 19 which which WDT cord-002542-f7l4ty2j 338 20 appears appear VBZ cord-002542-f7l4ty2j 338 21 at at IN cord-002542-f7l4ty2j 338 22 low low JJ cord-002542-f7l4ty2j 338 23 levels level NNS cord-002542-f7l4ty2j 338 24 as as RB cord-002542-f7l4ty2j 338 25 early early RB cord-002542-f7l4ty2j 338 26 as as IN cord-002542-f7l4ty2j 338 27 passage passage NN cord-002542-f7l4ty2j 338 28 2 2 CD cord-002542-f7l4ty2j 338 29 , , , cord-002542-f7l4ty2j 338 30 but but CC cord-002542-f7l4ty2j 338 31 does do VBZ cord-002542-f7l4ty2j 338 32 not not RB cord-002542-f7l4ty2j 338 33 begin begin VB cord-002542-f7l4ty2j 338 34 to to TO cord-002542-f7l4ty2j 338 35 accumulate accumulate VB cord-002542-f7l4ty2j 338 36 until until IN cord-002542-f7l4ty2j 338 37 passage passage NN cord-002542-f7l4ty2j 338 38 6 6 CD cord-002542-f7l4ty2j 338 39 ( ( -LRB- cord-002542-f7l4ty2j 338 40 S2 S2 NNP cord-002542-f7l4ty2j 338 41 Datafile Datafile NNP cord-002542-f7l4ty2j 338 42 ) ) -RRB- cord-002542-f7l4ty2j 338 43 . . . cord-002542-f7l4ty2j 339 1 Why why WRB cord-002542-f7l4ty2j 339 2 this this DT cord-002542-f7l4ty2j 339 3 DI DI NNP cord-002542-f7l4ty2j 339 4 - - HYPH cord-002542-f7l4ty2j 339 5 RNA RNA NNP cord-002542-f7l4ty2j 339 6 only only RB cord-002542-f7l4ty2j 339 7 begins begin VBZ cord-002542-f7l4ty2j 339 8 to to TO cord-002542-f7l4ty2j 339 9 accumulate accumulate VB cord-002542-f7l4ty2j 339 10 at at IN cord-002542-f7l4ty2j 339 11 later later JJ cord-002542-f7l4ty2j 339 12 passages passage NNS cord-002542-f7l4ty2j 339 13 despite despite IN cord-002542-f7l4ty2j 339 14 being be VBG cord-002542-f7l4ty2j 339 15 present present JJ cord-002542-f7l4ty2j 339 16 in in IN cord-002542-f7l4ty2j 339 17 the the DT cord-002542-f7l4ty2j 339 18 early early JJ cord-002542-f7l4ty2j 339 19 passages passage NNS cord-002542-f7l4ty2j 339 20 is be VBZ cord-002542-f7l4ty2j 339 21 not not RB cord-002542-f7l4ty2j 339 22 clear clear JJ cord-002542-f7l4ty2j 339 23 . . . cord-002542-f7l4ty2j 340 1 The the DT cord-002542-f7l4ty2j 340 2 ' ' `` cord-002542-f7l4ty2j 340 3 complex complex JJ cord-002542-f7l4ty2j 340 4 DI DI NNP cord-002542-f7l4ty2j 340 5 - - HYPH cord-002542-f7l4ty2j 340 6 RNA RNA NNP cord-002542-f7l4ty2j 340 7 ' ' '' cord-002542-f7l4ty2j 340 8 that that WDT cord-002542-f7l4ty2j 340 9 deletes delete VBZ cord-002542-f7l4ty2j 340 10 the the DT cord-002542-f7l4ty2j 340 11 PSCE PSCE NNPS cord-002542-f7l4ty2j 340 12 in in IN cord-002542-f7l4ty2j 340 13 RNA1 RNA1 NNP cord-002542-f7l4ty2j 340 14 referred refer VBD cord-002542-f7l4ty2j 340 15 to to IN cord-002542-f7l4ty2j 340 16 in in IN cord-002542-f7l4ty2j 340 17 the the DT cord-002542-f7l4ty2j 340 18 previous previous JJ cord-002542-f7l4ty2j 340 19 section section NN cord-002542-f7l4ty2j 340 20 ( ( -LRB- cord-002542-f7l4ty2j 340 21 ' ' `` cord-002542-f7l4ty2j 340 22 1_342 1_342 CD cord-002542-f7l4ty2j 340 23 ^ ^ NFP cord-002542-f7l4ty2j 340 24 1083_1245 1083_1245 CD cord-002542-f7l4ty2j 340 25 ^ ^ : cord-002542-f7l4ty2j 340 26 2514_3107 2514_3107 NNP cord-002542-f7l4ty2j 340 27 ' ' '' cord-002542-f7l4ty2j 340 28 ) ) -RRB- cord-002542-f7l4ty2j 340 29 is be VBZ cord-002542-f7l4ty2j 340 30 also also RB cord-002542-f7l4ty2j 340 31 observed observe VBN cord-002542-f7l4ty2j 340 32 ( ( -LRB- cord-002542-f7l4ty2j 340 33 annotated annotate VBN cord-002542-f7l4ty2j 340 34 in in IN cord-002542-f7l4ty2j 340 35 Fig Fig NNP cord-002542-f7l4ty2j 340 36 6A 6a CD cord-002542-f7l4ty2j 340 37 ) ) -RRB- cord-002542-f7l4ty2j 340 38 first first RB cord-002542-f7l4ty2j 340 39 appearing appear VBG cord-002542-f7l4ty2j 340 40 at at IN cord-002542-f7l4ty2j 340 41 passage passage NN cord-002542-f7l4ty2j 340 42 5 5 CD cord-002542-f7l4ty2j 340 43 . . . cord-002542-f7l4ty2j 341 1 As as IN cord-002542-f7l4ty2j 341 2 can can MD cord-002542-f7l4ty2j 341 3 be be VB cord-002542-f7l4ty2j 341 4 seen see VBN cord-002542-f7l4ty2j 341 5 in in IN cord-002542-f7l4ty2j 341 6 the the DT cord-002542-f7l4ty2j 341 7 stacked stack VBN cord-002542-f7l4ty2j 341 8 area area NN cord-002542-f7l4ty2j 341 9 plot plot NN cord-002542-f7l4ty2j 341 10 for for IN cord-002542-f7l4ty2j 341 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 341 12 ( ( -LRB- cord-002542-f7l4ty2j 341 13 Fig Fig NNP cord-002542-f7l4ty2j 341 14 6B 6b CD cord-002542-f7l4ty2j 341 15 ) ) -RRB- cord-002542-f7l4ty2j 341 16 , , , cord-002542-f7l4ty2j 341 17 the the DT cord-002542-f7l4ty2j 341 18 general general JJ cord-002542-f7l4ty2j 341 19 composition composition NN cord-002542-f7l4ty2j 341 20 of of IN cord-002542-f7l4ty2j 341 21 DI DI NNP cord-002542-f7l4ty2j 341 22 - - HYPH cord-002542-f7l4ty2j 341 23 RNA RNA NNP cord-002542-f7l4ty2j 341 24 species specie NNS cord-002542-f7l4ty2j 341 25 is be VBZ cord-002542-f7l4ty2j 341 26 established establish VBN cord-002542-f7l4ty2j 341 27 at at IN cord-002542-f7l4ty2j 341 28 passages passage NNS cord-002542-f7l4ty2j 341 29 4 4 CD cord-002542-f7l4ty2j 341 30 - - SYM cord-002542-f7l4ty2j 341 31 5 5 CD cord-002542-f7l4ty2j 341 32 . . . cord-002542-f7l4ty2j 342 1 Subsequently subsequently RB cord-002542-f7l4ty2j 342 2 , , , cord-002542-f7l4ty2j 342 3 the the DT cord-002542-f7l4ty2j 342 4 relative relative JJ cord-002542-f7l4ty2j 342 5 frequencies frequency NNS cord-002542-f7l4ty2j 342 6 of of IN cord-002542-f7l4ty2j 342 7 the the DT cord-002542-f7l4ty2j 342 8 DI DI NNP cord-002542-f7l4ty2j 342 9 - - HYPH cord-002542-f7l4ty2j 342 10 RNA RNA NNP cord-002542-f7l4ty2j 342 11 fluctuate fluctuate VBP cord-002542-f7l4ty2j 342 12 but but CC cord-002542-f7l4ty2j 342 13 the the DT cord-002542-f7l4ty2j 342 14 overall overall JJ cord-002542-f7l4ty2j 342 15 diversity diversity NN cord-002542-f7l4ty2j 342 16 changes change VBZ cord-002542-f7l4ty2j 342 17 little little JJ cord-002542-f7l4ty2j 342 18 with with IN cord-002542-f7l4ty2j 342 19 few few JJ cord-002542-f7l4ty2j 342 20 new new JJ cord-002542-f7l4ty2j 342 21 species specie NNS cord-002542-f7l4ty2j 342 22 appearing appear VBG cord-002542-f7l4ty2j 342 23 after after IN cord-002542-f7l4ty2j 342 24 passage passage NN cord-002542-f7l4ty2j 342 25 4 4 CD cord-002542-f7l4ty2j 342 26 . . . cord-002542-f7l4ty2j 343 1 This this DT cord-002542-f7l4ty2j 343 2 is be VBZ cord-002542-f7l4ty2j 343 3 also also RB cord-002542-f7l4ty2j 343 4 observed observe VBN cord-002542-f7l4ty2j 343 5 when when WRB cord-002542-f7l4ty2j 343 6 calculating calculate VBG cord-002542-f7l4ty2j 343 7 the the DT cord-002542-f7l4ty2j 343 8 Shannon Shannon NNP cord-002542-f7l4ty2j 343 9 Diversity Diversity NNP cord-002542-f7l4ty2j 343 10 index index NN cord-002542-f7l4ty2j 343 11 ( ( -LRB- cord-002542-f7l4ty2j 343 12 Fig Fig NNP cord-002542-f7l4ty2j 343 13 5B 5b NN cord-002542-f7l4ty2j 343 14 ) ) -RRB- cord-002542-f7l4ty2j 343 15 whereby whereby WRB cord-002542-f7l4ty2j 343 16 entropy entropy NN cord-002542-f7l4ty2j 343 17 reaches reach VBZ cord-002542-f7l4ty2j 343 18 a a DT cord-002542-f7l4ty2j 343 19 maximum maximum NN cord-002542-f7l4ty2j 343 20 at at IN cord-002542-f7l4ty2j 343 21 passage passage NN cord-002542-f7l4ty2j 343 22 5 5 CD cord-002542-f7l4ty2j 343 23 and and CC cord-002542-f7l4ty2j 343 24 decreases decrease VBZ cord-002542-f7l4ty2j 343 25 thereafter thereafter RB cord-002542-f7l4ty2j 343 26 . . . cord-002542-f7l4ty2j 344 1 Interestingly interestingly RB cord-002542-f7l4ty2j 344 2 , , , cord-002542-f7l4ty2j 344 3 this this DT cord-002542-f7l4ty2j 344 4 range range NN cord-002542-f7l4ty2j 344 5 of of IN cord-002542-f7l4ty2j 344 6 fluctuations fluctuation NNS cord-002542-f7l4ty2j 344 7 resemble resemble VBP cord-002542-f7l4ty2j 344 8 the the DT cord-002542-f7l4ty2j 344 9 sinusoidal sinusoidal JJ cord-002542-f7l4ty2j 344 10 patterns pattern NNS cord-002542-f7l4ty2j 344 11 of of IN cord-002542-f7l4ty2j 344 12 DI DI NNP cord-002542-f7l4ty2j 344 13 - - HYPH cord-002542-f7l4ty2j 344 14 RNA RNA NNP cord-002542-f7l4ty2j 344 15 abundance abundance NN cord-002542-f7l4ty2j 344 16 that that WDT cord-002542-f7l4ty2j 344 17 have have VBP cord-002542-f7l4ty2j 344 18 been be VBN cord-002542-f7l4ty2j 344 19 observed observe VBN cord-002542-f7l4ty2j 344 20 in in IN cord-002542-f7l4ty2j 344 21 other other JJ cord-002542-f7l4ty2j 344 22 studies study NNS cord-002542-f7l4ty2j 344 23 of of IN cord-002542-f7l4ty2j 344 24 RNA RNA NNP cord-002542-f7l4ty2j 344 25 viruses virus NNS cord-002542-f7l4ty2j 344 26 where where WRB cord-002542-f7l4ty2j 344 27 the the DT cord-002542-f7l4ty2j 344 28 ratio ratio NN cord-002542-f7l4ty2j 344 29 of of IN cord-002542-f7l4ty2j 344 30 the the DT cord-002542-f7l4ty2j 344 31 frequency frequency NN cord-002542-f7l4ty2j 344 32 of of IN cord-002542-f7l4ty2j 344 33 DI DI NNP cord-002542-f7l4ty2j 344 34 - - HYPH cord-002542-f7l4ty2j 344 35 RNAs rna NNS cord-002542-f7l4ty2j 344 36 to to IN cord-002542-f7l4ty2j 344 37 wildtype wildtype NN cord-002542-f7l4ty2j 344 38 genome genome NN cord-002542-f7l4ty2j 344 39 has have VBZ cord-002542-f7l4ty2j 344 40 been be VBN cord-002542-f7l4ty2j 344 41 measured measure VBN cord-002542-f7l4ty2j 344 42 through through IN cord-002542-f7l4ty2j 344 43 longitudinal longitudinal JJ cord-002542-f7l4ty2j 344 44 studies study NNS cord-002542-f7l4ty2j 344 45 [ [ -LRB- cord-002542-f7l4ty2j 344 46 67 67 CD cord-002542-f7l4ty2j 344 47 ] ] -RRB- cord-002542-f7l4ty2j 344 48 . . . cord-002542-f7l4ty2j 345 1 The the DT cord-002542-f7l4ty2j 345 2 reduction reduction NN cord-002542-f7l4ty2j 345 3 in in IN cord-002542-f7l4ty2j 345 4 full full JJ cord-002542-f7l4ty2j 345 5 - - HYPH cord-002542-f7l4ty2j 345 6 length length NN cord-002542-f7l4ty2j 345 7 infectious infectious JJ cord-002542-f7l4ty2j 345 8 viral viral JJ cord-002542-f7l4ty2j 345 9 genomes genome NNS cord-002542-f7l4ty2j 345 10 and and CC cord-002542-f7l4ty2j 345 11 the the DT cord-002542-f7l4ty2j 345 12 accumulation accumulation NN cord-002542-f7l4ty2j 345 13 of of IN cord-002542-f7l4ty2j 345 14 defective defective JJ cord-002542-f7l4ty2j 345 15 RNAs rna NNS cord-002542-f7l4ty2j 345 16 during during IN cord-002542-f7l4ty2j 345 17 passaging passaging NN cord-002542-f7l4ty2j 345 18 is be VBZ cord-002542-f7l4ty2j 345 19 likely likely JJ cord-002542-f7l4ty2j 345 20 to to TO cord-002542-f7l4ty2j 345 21 correspond correspond VB cord-002542-f7l4ty2j 345 22 to to IN cord-002542-f7l4ty2j 345 23 a a DT cord-002542-f7l4ty2j 345 24 decrease decrease NN cord-002542-f7l4ty2j 345 25 in in IN cord-002542-f7l4ty2j 345 26 the the DT cord-002542-f7l4ty2j 345 27 specific specific JJ cord-002542-f7l4ty2j 345 28 infectivity infectivity NN cord-002542-f7l4ty2j 345 29 of of IN cord-002542-f7l4ty2j 345 30 the the DT cord-002542-f7l4ty2j 345 31 virus virus NN cord-002542-f7l4ty2j 345 32 samples sample NNS cord-002542-f7l4ty2j 345 33 . . . cord-002542-f7l4ty2j 346 1 To to TO cord-002542-f7l4ty2j 346 2 determine determine VB cord-002542-f7l4ty2j 346 3 the the DT cord-002542-f7l4ty2j 346 4 effect effect NN cord-002542-f7l4ty2j 346 5 of of IN cord-002542-f7l4ty2j 346 6 defective defective JJ cord-002542-f7l4ty2j 346 7 RNAs rna NNS cord-002542-f7l4ty2j 346 8 characterized characterize VBN cord-002542-f7l4ty2j 346 9 by by IN cord-002542-f7l4ty2j 346 10 combined combine VBN cord-002542-f7l4ty2j 346 11 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 346 12 and and CC cord-002542-f7l4ty2j 346 13 nanopore nanopore NNP cord-002542-f7l4ty2j 346 14 sequencing sequencing NN cord-002542-f7l4ty2j 346 15 of of IN cord-002542-f7l4ty2j 346 16 replicate replicate VBP cord-002542-f7l4ty2j 346 17 2 2 CD cord-002542-f7l4ty2j 346 18 upon upon IN cord-002542-f7l4ty2j 346 19 specific specific JJ cord-002542-f7l4ty2j 346 20 infectivity infectivity NN cord-002542-f7l4ty2j 346 21 , , , cord-002542-f7l4ty2j 346 22 we -PRON- PRP cord-002542-f7l4ty2j 346 23 performed perform VBD cord-002542-f7l4ty2j 346 24 50 50 CD cord-002542-f7l4ty2j 346 25 % % NN cord-002542-f7l4ty2j 346 26 tissue tissue NN cord-002542-f7l4ty2j 346 27 culture culture NN cord-002542-f7l4ty2j 346 28 infectious infectious JJ cord-002542-f7l4ty2j 346 29 dose dose NN cord-002542-f7l4ty2j 347 1 ( ( -LRB- cord-002542-f7l4ty2j 347 2 TCID50 TCID50 NNP cord-002542-f7l4ty2j 347 3 ) ) -RRB- cord-002542-f7l4ty2j 347 4 assays assay NNS cord-002542-f7l4ty2j 347 5 for for IN cord-002542-f7l4ty2j 347 6 each each DT cord-002542-f7l4ty2j 347 7 passage passage NN cord-002542-f7l4ty2j 347 8 1 1 CD cord-002542-f7l4ty2j 347 9 - - SYM cord-002542-f7l4ty2j 347 10 9 9 CD cord-002542-f7l4ty2j 347 11 for for IN cord-002542-f7l4ty2j 347 12 both both CC cord-002542-f7l4ty2j 347 13 the the DT cord-002542-f7l4ty2j 347 14 original original JJ cord-002542-f7l4ty2j 347 15 inoculum inoculum NN cord-002542-f7l4ty2j 347 16 used use VBN cord-002542-f7l4ty2j 347 17 to to TO cord-002542-f7l4ty2j 347 18 infect infect VB cord-002542-f7l4ty2j 347 19 each each DT cord-002542-f7l4ty2j 347 20 sample sample NN cord-002542-f7l4ty2j 347 21 and and CC cord-002542-f7l4ty2j 347 22 for for IN cord-002542-f7l4ty2j 347 23 the the DT cord-002542-f7l4ty2j 347 24 particles particle NNS cord-002542-f7l4ty2j 347 25 purified purify VBN cord-002542-f7l4ty2j 347 26 from from IN cord-002542-f7l4ty2j 347 27 each each DT cord-002542-f7l4ty2j 347 28 passage passage NN cord-002542-f7l4ty2j 347 29 [ [ -LRB- cord-002542-f7l4ty2j 347 30 51 51 CD cord-002542-f7l4ty2j 347 31 ] ] -RRB- cord-002542-f7l4ty2j 347 32 . . . cord-002542-f7l4ty2j 348 1 The the DT cord-002542-f7l4ty2j 348 2 TCID50 TCID50 NNP cord-002542-f7l4ty2j 348 3 assay assay NN cord-002542-f7l4ty2j 348 4 is be VBZ cord-002542-f7l4ty2j 348 5 used use VBN cord-002542-f7l4ty2j 348 6 to to TO cord-002542-f7l4ty2j 348 7 determine determine VB cord-002542-f7l4ty2j 348 8 the the DT cord-002542-f7l4ty2j 348 9 dose dose NN cord-002542-f7l4ty2j 348 10 required require VBN cord-002542-f7l4ty2j 348 11 to to TO cord-002542-f7l4ty2j 348 12 give give VB cord-002542-f7l4ty2j 348 13 a a DT cord-002542-f7l4ty2j 348 14 50 50 CD cord-002542-f7l4ty2j 348 15 % % NN cord-002542-f7l4ty2j 348 16 chance chance NN cord-002542-f7l4ty2j 348 17 that that IN cord-002542-f7l4ty2j 348 18 cells cell NNS cord-002542-f7l4ty2j 348 19 in in IN cord-002542-f7l4ty2j 348 20 culture culture NN cord-002542-f7l4ty2j 348 21 will will MD cord-002542-f7l4ty2j 348 22 be be VB cord-002542-f7l4ty2j 348 23 successfully successfully RB cord-002542-f7l4ty2j 348 24 infected infect VBN cord-002542-f7l4ty2j 348 25 as as IN cord-002542-f7l4ty2j 348 26 determined determine VBN cord-002542-f7l4ty2j 348 27 by by IN cord-002542-f7l4ty2j 348 28 CPE CPE NNP cord-002542-f7l4ty2j 348 29 and and CC cord-002542-f7l4ty2j 348 30 is be VBZ cord-002542-f7l4ty2j 348 31 typically typically RB cord-002542-f7l4ty2j 348 32 used use VBN cord-002542-f7l4ty2j 348 33 to to TO cord-002542-f7l4ty2j 348 34 determine determine VB cord-002542-f7l4ty2j 348 35 viral viral JJ cord-002542-f7l4ty2j 348 36 titer titer NN cord-002542-f7l4ty2j 348 37 and and CC cord-002542-f7l4ty2j 348 38 the the DT cord-002542-f7l4ty2j 348 39 effective effective JJ cord-002542-f7l4ty2j 348 40 MOI MOI NNP cord-002542-f7l4ty2j 348 41 of of IN cord-002542-f7l4ty2j 348 42 the the DT cord-002542-f7l4ty2j 348 43 inocula inocula NNP cord-002542-f7l4ty2j 348 44 transferred transfer VBN cord-002542-f7l4ty2j 348 45 from from IN cord-002542-f7l4ty2j 348 46 passage passage NN cord-002542-f7l4ty2j 348 47 to to IN cord-002542-f7l4ty2j 348 48 passage passage NN cord-002542-f7l4ty2j 348 49 . . . cord-002542-f7l4ty2j 349 1 The the DT cord-002542-f7l4ty2j 349 2 results result NNS cord-002542-f7l4ty2j 349 3 from from IN cord-002542-f7l4ty2j 349 4 the the DT cord-002542-f7l4ty2j 349 5 TCID50 tcid50 CD cord-002542-f7l4ty2j 349 6 assay assay NN cord-002542-f7l4ty2j 349 7 for for IN cord-002542-f7l4ty2j 349 8 each each DT cord-002542-f7l4ty2j 349 9 passage passage NN cord-002542-f7l4ty2j 349 10 are be VBP cord-002542-f7l4ty2j 349 11 shown show VBN cord-002542-f7l4ty2j 349 12 in in IN cord-002542-f7l4ty2j 349 13 Fig Fig NNP cord-002542-f7l4ty2j 349 14 7A 7a NN cord-002542-f7l4ty2j 349 15 and and CC cord-002542-f7l4ty2j 349 16 7B 7b NN cord-002542-f7l4ty2j 349 17 . . . cord-002542-f7l4ty2j 350 1 We -PRON- PRP cord-002542-f7l4ty2j 350 2 found find VBD cord-002542-f7l4ty2j 350 3 that that IN cord-002542-f7l4ty2j 350 4 the the DT cord-002542-f7l4ty2j 350 5 TCID50 TCID50 NNP cord-002542-f7l4ty2j 350 6 value value NN cord-002542-f7l4ty2j 350 7 ( ( -LRB- cord-002542-f7l4ty2j 350 8 and and CC cord-002542-f7l4ty2j 350 9 thus thus RB cord-002542-f7l4ty2j 350 10 PFUs(Plaque PFUs(Plaque NNP cord-002542-f7l4ty2j 350 11 Forming Forming NNP cord-002542-f7l4ty2j 350 12 Units)/ml Units)/ml NNS cord-002542-f7l4ty2j 350 13 ) ) -RRB- cord-002542-f7l4ty2j 350 14 drops drop VBZ cord-002542-f7l4ty2j 350 15 considerably considerably RB cord-002542-f7l4ty2j 350 16 during during IN cord-002542-f7l4ty2j 350 17 passaging passage VBG cord-002542-f7l4ty2j 350 18 by by IN cord-002542-f7l4ty2j 350 19 over over IN cord-002542-f7l4ty2j 350 20 four four CD cord-002542-f7l4ty2j 350 21 orders order NNS cord-002542-f7l4ty2j 350 22 of of IN cord-002542-f7l4ty2j 350 23 magnitude magnitude NN cord-002542-f7l4ty2j 350 24 . . . cord-002542-f7l4ty2j 351 1 The the DT cord-002542-f7l4ty2j 351 2 corresponding corresponding JJ cord-002542-f7l4ty2j 351 3 effective effective JJ cord-002542-f7l4ty2j 351 4 MOI MOI NNP cord-002542-f7l4ty2j 351 5 ( ( -LRB- cord-002542-f7l4ty2j 351 6 PFUs pfus NN cord-002542-f7l4ty2j 351 7 per per IN cord-002542-f7l4ty2j 351 8 cell cell NN cord-002542-f7l4ty2j 351 9 ) ) -RRB- cord-002542-f7l4ty2j 351 10 also also RB cord-002542-f7l4ty2j 351 11 drops drop VBZ cord-002542-f7l4ty2j 351 12 from from IN cord-002542-f7l4ty2j 351 13 38.5 38.5 CD cord-002542-f7l4ty2j 351 14 to to IN cord-002542-f7l4ty2j 351 15 0.0003 0.0003 CD cord-002542-f7l4ty2j 351 16 during during IN cord-002542-f7l4ty2j 351 17 passaging passaging NN cord-002542-f7l4ty2j 351 18 ( ( -LRB- cord-002542-f7l4ty2j 351 19 Fig Fig NNP cord-002542-f7l4ty2j 351 20 7B 7b NN cord-002542-f7l4ty2j 351 21 ) ) -RRB- cord-002542-f7l4ty2j 351 22 . . . cord-002542-f7l4ty2j 352 1 and and CC cord-002542-f7l4ty2j 352 2 ( ( -LRB- cord-002542-f7l4ty2j 352 3 B b NN cord-002542-f7l4ty2j 352 4 ) ) -RRB- cord-002542-f7l4ty2j 352 5 RNA2 RNA2 NNP cord-002542-f7l4ty2j 352 6 . . . cord-002542-f7l4ty2j 353 1 The the DT cord-002542-f7l4ty2j 353 2 passage passage NN cord-002542-f7l4ty2j 353 3 number number NN cord-002542-f7l4ty2j 353 4 is be VBZ cord-002542-f7l4ty2j 353 5 indicated indicate VBN cord-002542-f7l4ty2j 353 6 on on IN cord-002542-f7l4ty2j 353 7 the the DT cord-002542-f7l4ty2j 353 8 x x NN cord-002542-f7l4ty2j 353 9 - - HYPH cord-002542-f7l4ty2j 353 10 axis axis NN cord-002542-f7l4ty2j 353 11 and and CC cord-002542-f7l4ty2j 353 12 the the DT cord-002542-f7l4ty2j 353 13 stacked stacked JJ cord-002542-f7l4ty2j 353 14 frequencies frequency NNS cord-002542-f7l4ty2j 353 15 of of IN cord-002542-f7l4ty2j 353 16 each each DT cord-002542-f7l4ty2j 353 17 detected detect VBN cord-002542-f7l4ty2j 353 18 defective defective JJ cord-002542-f7l4ty2j 353 19 RNA RNA NNP cord-002542-f7l4ty2j 353 20 is be VBZ cord-002542-f7l4ty2j 353 21 shown show VBN cord-002542-f7l4ty2j 353 22 in in IN cord-002542-f7l4ty2j 353 23 the the DT cord-002542-f7l4ty2j 353 24 y y NN cord-002542-f7l4ty2j 353 25 - - HYPH cord-002542-f7l4ty2j 353 26 axis axis NN cord-002542-f7l4ty2j 353 27 . . . cord-002542-f7l4ty2j 354 1 Each each DT cord-002542-f7l4ty2j 354 2 non non JJ cord-002542-f7l4ty2j 354 3 - - JJ cord-002542-f7l4ty2j 354 4 contiguous contiguous JJ cord-002542-f7l4ty2j 354 5 color color NN cord-002542-f7l4ty2j 354 6 represents represent VBZ cord-002542-f7l4ty2j 354 7 a a DT cord-002542-f7l4ty2j 354 8 specific specific JJ cord-002542-f7l4ty2j 354 9 genome genome NN cord-002542-f7l4ty2j 354 10 characterized characterize VBN cord-002542-f7l4ty2j 354 11 by by IN cord-002542-f7l4ty2j 354 12 MinION MinION VBG cord-002542-f7l4ty2j 354 13 nanopore nanopore NNP cord-002542-f7l4ty2j 354 14 sequencing sequencing NN cord-002542-f7l4ty2j 354 15 . . . cord-002542-f7l4ty2j 355 1 Wild wild JJ cord-002542-f7l4ty2j 355 2 - - HYPH cord-002542-f7l4ty2j 355 3 type type NN cord-002542-f7l4ty2j 355 4 genomes genome NNS cord-002542-f7l4ty2j 355 5 are be VBP cord-002542-f7l4ty2j 355 6 colored color VBN cord-002542-f7l4ty2j 355 7 green green JJ cord-002542-f7l4ty2j 355 8 , , , cord-002542-f7l4ty2j 355 9 genomes genome NNS cord-002542-f7l4ty2j 355 10 with with IN cord-002542-f7l4ty2j 355 11 one one CD cord-002542-f7l4ty2j 355 12 deletion deletion NN cord-002542-f7l4ty2j 355 13 are be VBP cord-002542-f7l4ty2j 355 14 colored color VBN cord-002542-f7l4ty2j 355 15 in in IN cord-002542-f7l4ty2j 355 16 shades shade NNS cord-002542-f7l4ty2j 355 17 of of IN cord-002542-f7l4ty2j 355 18 blue blue JJ cord-002542-f7l4ty2j 355 19 , , , cord-002542-f7l4ty2j 355 20 and and CC cord-002542-f7l4ty2j 355 21 genomes genome NNS cord-002542-f7l4ty2j 355 22 with with IN cord-002542-f7l4ty2j 355 23 two two CD cord-002542-f7l4ty2j 355 24 or or CC cord-002542-f7l4ty2j 355 25 more more JJR cord-002542-f7l4ty2j 355 26 deletions deletion NNS cord-002542-f7l4ty2j 355 27 are be VBP cord-002542-f7l4ty2j 355 28 colored color VBN cord-002542-f7l4ty2j 355 29 in in IN cord-002542-f7l4ty2j 355 30 shades shade NNS cord-002542-f7l4ty2j 355 31 of of IN cord-002542-f7l4ty2j 355 32 orange orange NN cord-002542-f7l4ty2j 355 33 ( ( -LRB- cord-002542-f7l4ty2j 355 34 using use VBG cord-002542-f7l4ty2j 355 35 the the DT cord-002542-f7l4ty2j 355 36 same same JJ cord-002542-f7l4ty2j 355 37 color color NN cord-002542-f7l4ty2j 355 38 scheme scheme NN cord-002542-f7l4ty2j 355 39 as as IN cord-002542-f7l4ty2j 355 40 in in IN cord-002542-f7l4ty2j 355 41 Fig Fig NNP cord-002542-f7l4ty2j 355 42 5B 5b NN cord-002542-f7l4ty2j 355 43 ) ) -RRB- cord-002542-f7l4ty2j 355 44 . . . cord-002542-f7l4ty2j 356 1 Raw raw JJ cord-002542-f7l4ty2j 356 2 data datum NNS cord-002542-f7l4ty2j 356 3 and and CC cord-002542-f7l4ty2j 356 4 annotations annotation NNS cord-002542-f7l4ty2j 356 5 are be VBP cord-002542-f7l4ty2j 356 6 in in IN cord-002542-f7l4ty2j 356 7 S2 S2 NNP cord-002542-f7l4ty2j 356 8 Datafile Datafile NNP cord-002542-f7l4ty2j 356 9 . . . cord-002542-f7l4ty2j 357 1 To to TO cord-002542-f7l4ty2j 357 2 determine determine VB cord-002542-f7l4ty2j 357 3 whether whether IN cord-002542-f7l4ty2j 357 4 the the DT cord-002542-f7l4ty2j 357 5 drop drop NN cord-002542-f7l4ty2j 357 6 in in IN cord-002542-f7l4ty2j 357 7 effective effective JJ cord-002542-f7l4ty2j 357 8 MOI MOI NNP cord-002542-f7l4ty2j 357 9 was be VBD cord-002542-f7l4ty2j 357 10 driven drive VBN cord-002542-f7l4ty2j 357 11 by by IN cord-002542-f7l4ty2j 357 12 reduced reduce VBN cord-002542-f7l4ty2j 357 13 total total JJ cord-002542-f7l4ty2j 357 14 particle particle NN cord-002542-f7l4ty2j 357 15 yield yield NN cord-002542-f7l4ty2j 357 16 or or CC cord-002542-f7l4ty2j 357 17 from from IN cord-002542-f7l4ty2j 357 18 reduced reduce VBN cord-002542-f7l4ty2j 357 19 specific specific JJ cord-002542-f7l4ty2j 357 20 infectivity infectivity NN cord-002542-f7l4ty2j 357 21 ( ( -LRB- cord-002542-f7l4ty2j 357 22 i.e. i.e. FW cord-002542-f7l4ty2j 357 23 virus virus NN cord-002542-f7l4ty2j 357 24 particles particle NNS cord-002542-f7l4ty2j 357 25 per per IN cord-002542-f7l4ty2j 357 26 PFU pfu NN cord-002542-f7l4ty2j 357 27 ) ) -RRB- cord-002542-f7l4ty2j 357 28 , , , cord-002542-f7l4ty2j 357 29 we -PRON- PRP cord-002542-f7l4ty2j 357 30 also also RB cord-002542-f7l4ty2j 357 31 performed perform VBD cord-002542-f7l4ty2j 357 32 TCID50 TCID50 NNP cord-002542-f7l4ty2j 357 33 analysis analysis NN cord-002542-f7l4ty2j 357 34 of of IN cord-002542-f7l4ty2j 357 35 our -PRON- PRP$ cord-002542-f7l4ty2j 357 36 purified purify VBN cord-002542-f7l4ty2j 357 37 and and CC cord-002542-f7l4ty2j 357 38 quantified quantify VBN cord-002542-f7l4ty2j 357 39 virus virus NN cord-002542-f7l4ty2j 357 40 stocks stock NNS cord-002542-f7l4ty2j 357 41 ( ( -LRB- cord-002542-f7l4ty2j 357 42 described describe VBN cord-002542-f7l4ty2j 357 43 in in IN cord-002542-f7l4ty2j 357 44 methods method NNS cord-002542-f7l4ty2j 357 45 ) ) -RRB- cord-002542-f7l4ty2j 357 46 . . . cord-002542-f7l4ty2j 358 1 This this DT cord-002542-f7l4ty2j 358 2 allowed allow VBD cord-002542-f7l4ty2j 358 3 us -PRON- PRP cord-002542-f7l4ty2j 358 4 to to IN cord-002542-f7l4ty2j 358 5 Pathways pathway NNS cord-002542-f7l4ty2j 358 6 of of IN cord-002542-f7l4ty2j 358 7 FHV FHV NNP cord-002542-f7l4ty2j 358 8 defective defective JJ cord-002542-f7l4ty2j 358 9 RNA RNA NNP cord-002542-f7l4ty2j 358 10 evolution evolution NN cord-002542-f7l4ty2j 358 11 by by IN cord-002542-f7l4ty2j 358 12 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 358 13 and and CC cord-002542-f7l4ty2j 358 14 the the DT cord-002542-f7l4ty2j 358 15 MinION minion NN cord-002542-f7l4ty2j 358 16 determine determine VBP cord-002542-f7l4ty2j 358 17 and and CC cord-002542-f7l4ty2j 358 18 normalize normalize VB cord-002542-f7l4ty2j 358 19 the the DT cord-002542-f7l4ty2j 358 20 number number NN cord-002542-f7l4ty2j 358 21 of of IN cord-002542-f7l4ty2j 358 22 virus virus NN cord-002542-f7l4ty2j 358 23 particles particle NNS cord-002542-f7l4ty2j 358 24 delivered deliver VBN cord-002542-f7l4ty2j 358 25 per per IN cord-002542-f7l4ty2j 358 26 cell cell NN cord-002542-f7l4ty2j 358 27 between between IN cord-002542-f7l4ty2j 358 28 each each DT cord-002542-f7l4ty2j 358 29 passage passage NN cord-002542-f7l4ty2j 358 30 . . . cord-002542-f7l4ty2j 359 1 As as IN cord-002542-f7l4ty2j 359 2 the the DT cord-002542-f7l4ty2j 359 3 particle particle NN cord-002542-f7l4ty2j 359 4 - - HYPH cord-002542-f7l4ty2j 359 5 per per IN cord-002542-f7l4ty2j 359 6 - - HYPH cord-002542-f7l4ty2j 359 7 PFU pfu NN cord-002542-f7l4ty2j 359 8 ratio ratio NN cord-002542-f7l4ty2j 359 9 has have VBZ cord-002542-f7l4ty2j 359 10 previously previously RB cord-002542-f7l4ty2j 359 11 been be VBN cord-002542-f7l4ty2j 359 12 estimated estimate VBN cord-002542-f7l4ty2j 359 13 at at IN cord-002542-f7l4ty2j 359 14 300 300 CD cord-002542-f7l4ty2j 359 15 - - SYM cord-002542-f7l4ty2j 359 16 400 400 CD cord-002542-f7l4ty2j 359 17 particles particle NNS cord-002542-f7l4ty2j 359 18 - - HYPH cord-002542-f7l4ty2j 359 19 per per FW cord-002542-f7l4ty2j 359 20 - - HYPH cord-002542-f7l4ty2j 359 21 PFU pfu NN cord-002542-f7l4ty2j 359 22 [ [ -LRB- cord-002542-f7l4ty2j 359 23 26 26 CD cord-002542-f7l4ty2j 359 24 , , , cord-002542-f7l4ty2j 359 25 52 52 CD cord-002542-f7l4ty2j 359 26 ] ] -RRB- cord-002542-f7l4ty2j 359 27 we -PRON- PRP cord-002542-f7l4ty2j 359 28 setup setup VBP cord-002542-f7l4ty2j 359 29 our -PRON- PRP$ cord-002542-f7l4ty2j 359 30 assay assay NN cord-002542-f7l4ty2j 359 31 beginning begin VBG cord-002542-f7l4ty2j 359 32 with with IN cord-002542-f7l4ty2j 359 33 300'000 300'000 CD cord-002542-f7l4ty2j 359 34 particles particle NNS cord-002542-f7l4ty2j 359 35 per per IN cord-002542-f7l4ty2j 359 36 cell cell NN cord-002542-f7l4ty2j 359 37 in in IN cord-002542-f7l4ty2j 359 38 96 96 CD cord-002542-f7l4ty2j 359 39 well well JJ cord-002542-f7l4ty2j 359 40 format format NN cord-002542-f7l4ty2j 359 41 and and CC cord-002542-f7l4ty2j 359 42 performed perform VBD cord-002542-f7l4ty2j 359 43 8 8 CD cord-002542-f7l4ty2j 359 44 10-fold 10-fold JJ cord-002542-f7l4ty2j 359 45 serial serial JJ cord-002542-f7l4ty2j 359 46 dilutions dilution NNS cord-002542-f7l4ty2j 359 47 . . . cord-002542-f7l4ty2j 360 1 In in IN cord-002542-f7l4ty2j 360 2 this this DT cord-002542-f7l4ty2j 360 3 assay assay NN cord-002542-f7l4ty2j 360 4 , , , cord-002542-f7l4ty2j 360 5 we -PRON- PRP cord-002542-f7l4ty2j 360 6 found find VBD cord-002542-f7l4ty2j 360 7 that that IN cord-002542-f7l4ty2j 360 8 the the DT cord-002542-f7l4ty2j 360 9 number number NN cord-002542-f7l4ty2j 360 10 of of IN cord-002542-f7l4ty2j 360 11 viral viral JJ cord-002542-f7l4ty2j 360 12 particles particle NNS cord-002542-f7l4ty2j 360 13 required require VBN cord-002542-f7l4ty2j 360 14 to to TO cord-002542-f7l4ty2j 360 15 induce induce VB cord-002542-f7l4ty2j 360 16 CPE CPE NNP cord-002542-f7l4ty2j 360 17 decreased decrease VBD cord-002542-f7l4ty2j 360 18 by by IN cord-002542-f7l4ty2j 360 19 over over IN cord-002542-f7l4ty2j 360 20 400-fold 400-fold CD cord-002542-f7l4ty2j 360 21 during during IN cord-002542-f7l4ty2j 360 22 passaging passaging NN cord-002542-f7l4ty2j 360 23 ( ( -LRB- cord-002542-f7l4ty2j 360 24 Fig Fig NNP cord-002542-f7l4ty2j 360 25 7A 7a NN cord-002542-f7l4ty2j 360 26 ) ) -RRB- cord-002542-f7l4ty2j 360 27 with with IN cord-002542-f7l4ty2j 360 28 a a DT cord-002542-f7l4ty2j 360 29 trend trend NN cord-002542-f7l4ty2j 360 30 very very RB cord-002542-f7l4ty2j 360 31 similar similar JJ cord-002542-f7l4ty2j 360 32 to to IN cord-002542-f7l4ty2j 360 33 that that DT cord-002542-f7l4ty2j 360 34 for for IN cord-002542-f7l4ty2j 360 35 the the DT cord-002542-f7l4ty2j 360 36 unpurified unpurified JJ cord-002542-f7l4ty2j 360 37 inocula inocula NNP cord-002542-f7l4ty2j 360 38 . . . cord-002542-f7l4ty2j 361 1 Together together RB cord-002542-f7l4ty2j 361 2 , , , cord-002542-f7l4ty2j 361 3 these these DT cord-002542-f7l4ty2j 361 4 data datum NNS cord-002542-f7l4ty2j 361 5 indicate indicate VBP cord-002542-f7l4ty2j 361 6 virus virus NN cord-002542-f7l4ty2j 361 7 specific specific JJ cord-002542-f7l4ty2j 361 8 infectivity infectivity NN cord-002542-f7l4ty2j 361 9 drops drop VBZ cord-002542-f7l4ty2j 361 10 with with IN cord-002542-f7l4ty2j 361 11 a a DT cord-002542-f7l4ty2j 361 12 corresponding corresponding JJ cord-002542-f7l4ty2j 361 13 increase increase NN cord-002542-f7l4ty2j 361 14 in in IN cord-002542-f7l4ty2j 361 15 the the DT cord-002542-f7l4ty2j 361 16 defective defective JJ cord-002542-f7l4ty2j 361 17 RNA RNA NNP cord-002542-f7l4ty2j 361 18 population population NN cord-002542-f7l4ty2j 361 19 . . . cord-002542-f7l4ty2j 362 1 There there EX cord-002542-f7l4ty2j 362 2 was be VBD cord-002542-f7l4ty2j 362 3 an an DT cord-002542-f7l4ty2j 362 4 exception exception NN cord-002542-f7l4ty2j 362 5 at at IN cord-002542-f7l4ty2j 362 6 passage passage NN cord-002542-f7l4ty2j 362 7 7 7 CD cord-002542-f7l4ty2j 363 1 where where WRB cord-002542-f7l4ty2j 363 2 TCID50 TCID50 NNP cord-002542-f7l4ty2j 364 1 actually actually RB cord-002542-f7l4ty2j 364 2 increased~5 increased~5 NNP cord-002542-f7l4ty2j 364 3 fold fold VB cord-002542-f7l4ty2j 364 4 from from IN cord-002542-f7l4ty2j 364 5 the the DT cord-002542-f7l4ty2j 364 6 previous previous JJ cord-002542-f7l4ty2j 364 7 passage passage NN cord-002542-f7l4ty2j 364 8 . . . cord-002542-f7l4ty2j 365 1 This this DT cord-002542-f7l4ty2j 365 2 could could MD cord-002542-f7l4ty2j 365 3 be be VB cord-002542-f7l4ty2j 365 4 correlated correlate VBN cord-002542-f7l4ty2j 365 5 to to IN cord-002542-f7l4ty2j 365 6 our -PRON- PRP$ cord-002542-f7l4ty2j 365 7 observation observation NN cord-002542-f7l4ty2j 365 8 of of IN cord-002542-f7l4ty2j 365 9 a a DT cord-002542-f7l4ty2j 365 10 decrease decrease NN cord-002542-f7l4ty2j 365 11 in in IN cord-002542-f7l4ty2j 365 12 the the DT cord-002542-f7l4ty2j 365 13 amount amount NN cord-002542-f7l4ty2j 365 14 of of IN cord-002542-f7l4ty2j 365 15 defective defective JJ cord-002542-f7l4ty2j 365 16 RNA2 RNA2 NNP cord-002542-f7l4ty2j 365 17 species specie NNS cord-002542-f7l4ty2j 365 18 in in IN cord-002542-f7l4ty2j 365 19 the the DT cord-002542-f7l4ty2j 365 20 MinION minion NN cord-002542-f7l4ty2j 365 21 analysis analysis NN cord-002542-f7l4ty2j 365 22 ( ( -LRB- cord-002542-f7l4ty2j 365 23 Figs Figs NNP cord-002542-f7l4ty2j 365 24 5B 5b NN cord-002542-f7l4ty2j 365 25 and and CC cord-002542-f7l4ty2j 365 26 6B 6b CD cord-002542-f7l4ty2j 365 27 ) ) -RRB- cord-002542-f7l4ty2j 365 28 . . . cord-002542-f7l4ty2j 366 1 We -PRON- PRP cord-002542-f7l4ty2j 366 2 further further RB cord-002542-f7l4ty2j 366 3 characterized characterize VBD cord-002542-f7l4ty2j 366 4 each each DT cord-002542-f7l4ty2j 366 5 well well NN cord-002542-f7l4ty2j 366 6 of of IN cord-002542-f7l4ty2j 366 7 the the DT cord-002542-f7l4ty2j 366 8 TCID50 TCID50 NNP cord-002542-f7l4ty2j 366 9 assay assay NN cord-002542-f7l4ty2j 366 10 of of IN cord-002542-f7l4ty2j 366 11 our -PRON- PRP$ cord-002542-f7l4ty2j 366 12 purified purify VBN cord-002542-f7l4ty2j 366 13 particles particle NNS cord-002542-f7l4ty2j 366 14 using use VBG cord-002542-f7l4ty2j 366 15 flowcytometry flowcytometry NN cord-002542-f7l4ty2j 366 16 to to TO cord-002542-f7l4ty2j 366 17 give give VB cord-002542-f7l4ty2j 366 18 a a DT cord-002542-f7l4ty2j 366 19 quantitative quantitative JJ cord-002542-f7l4ty2j 366 20 assessment assessment NN cord-002542-f7l4ty2j 366 21 of of IN cord-002542-f7l4ty2j 366 22 cell cell NN cord-002542-f7l4ty2j 366 23 survival survival NN cord-002542-f7l4ty2j 366 24 and and CC cord-002542-f7l4ty2j 366 25 death death NN cord-002542-f7l4ty2j 366 26 in in IN cord-002542-f7l4ty2j 366 27 response response NN cord-002542-f7l4ty2j 366 28 to to IN cord-002542-f7l4ty2j 366 29 virus virus NN cord-002542-f7l4ty2j 366 30 dose dose NN cord-002542-f7l4ty2j 366 31 . . . cord-002542-f7l4ty2j 367 1 We -PRON- PRP cord-002542-f7l4ty2j 367 2 calculated calculate VBD cord-002542-f7l4ty2j 367 3 the the DT cord-002542-f7l4ty2j 367 4 number number NN cord-002542-f7l4ty2j 367 5 of of IN cord-002542-f7l4ty2j 367 6 live live JJ cord-002542-f7l4ty2j 367 7 cells cell NNS cord-002542-f7l4ty2j 367 8 that that WDT cord-002542-f7l4ty2j 367 9 remained remain VBD cord-002542-f7l4ty2j 367 10 after after IN cord-002542-f7l4ty2j 367 11 infection infection NN cord-002542-f7l4ty2j 367 12 at at IN cord-002542-f7l4ty2j 367 13 each each DT cord-002542-f7l4ty2j 367 14 dilution dilution NN cord-002542-f7l4ty2j 367 15 and and CC cord-002542-f7l4ty2j 367 16 for for IN cord-002542-f7l4ty2j 367 17 each each DT cord-002542-f7l4ty2j 367 18 passage passage NN cord-002542-f7l4ty2j 368 1 ( ( -LRB- cord-002542-f7l4ty2j 368 2 Fig Fig NNP cord-002542-f7l4ty2j 368 3 7C 7C NNP cord-002542-f7l4ty2j 368 4 and and CC cord-002542-f7l4ty2j 368 5 S7 S7 NNP cord-002542-f7l4ty2j 368 6 Fig Fig NNP cord-002542-f7l4ty2j 368 7 ) ) -RRB- cord-002542-f7l4ty2j 368 8 . . . cord-002542-f7l4ty2j 369 1 We -PRON- PRP cord-002542-f7l4ty2j 369 2 observed observe VBD cord-002542-f7l4ty2j 369 3 a a DT cord-002542-f7l4ty2j 369 4 reduced reduced JJ cord-002542-f7l4ty2j 369 5 overall overall JJ cord-002542-f7l4ty2j 369 6 CPE CPE NNP cord-002542-f7l4ty2j 369 7 in in IN cord-002542-f7l4ty2j 369 8 later later JJ cord-002542-f7l4ty2j 369 9 passages passage NNS cord-002542-f7l4ty2j 369 10 at at IN cord-002542-f7l4ty2j 369 11 the the DT cord-002542-f7l4ty2j 369 12 highest high JJS cord-002542-f7l4ty2j 369 13 virus virus NN cord-002542-f7l4ty2j 369 14 dose dose NN cord-002542-f7l4ty2j 369 15 as as RB cord-002542-f7l4ty2j 369 16 well well RB cord-002542-f7l4ty2j 369 17 as as IN cord-002542-f7l4ty2j 369 18 an an DT cord-002542-f7l4ty2j 369 19 increase increase NN cord-002542-f7l4ty2j 369 20 in in IN cord-002542-f7l4ty2j 369 21 the the DT cord-002542-f7l4ty2j 369 22 number number NN cord-002542-f7l4ty2j 369 23 of of IN cord-002542-f7l4ty2j 369 24 viral viral JJ cord-002542-f7l4ty2j 369 25 particles particle NNS cord-002542-f7l4ty2j 369 26 require require VBP cord-002542-f7l4ty2j 369 27 to to TO cord-002542-f7l4ty2j 369 28 induce induce VB cord-002542-f7l4ty2j 369 29 the the DT cord-002542-f7l4ty2j 369 30 same same JJ cord-002542-f7l4ty2j 369 31 amount amount NN cord-002542-f7l4ty2j 369 32 of of IN cord-002542-f7l4ty2j 369 33 CPE CPE NNP cord-002542-f7l4ty2j 369 34 ( ( -LRB- cord-002542-f7l4ty2j 369 35 Fig Fig NNP cord-002542-f7l4ty2j 369 36 7C 7C NNP cord-002542-f7l4ty2j 369 37 ) ) -RRB- cord-002542-f7l4ty2j 369 38 . . . cord-002542-f7l4ty2j 370 1 Together together RB cord-002542-f7l4ty2j 370 2 these these DT cord-002542-f7l4ty2j 370 3 trends trend NNS cord-002542-f7l4ty2j 370 4 reflect reflect VBP cord-002542-f7l4ty2j 370 5 a a DT cord-002542-f7l4ty2j 370 6 reduced reduce VBN cord-002542-f7l4ty2j 370 7 specific specific JJ cord-002542-f7l4ty2j 370 8 infectivity infectivity NN cord-002542-f7l4ty2j 370 9 during during IN cord-002542-f7l4ty2j 370 10 viral viral JJ cord-002542-f7l4ty2j 370 11 passaging passaging NN cord-002542-f7l4ty2j 370 12 , , , cord-002542-f7l4ty2j 370 13 in in IN cord-002542-f7l4ty2j 370 14 agreement agreement NN cord-002542-f7l4ty2j 370 15 with with IN cord-002542-f7l4ty2j 370 16 our -PRON- PRP$ cord-002542-f7l4ty2j 370 17 TCID50 TCID50 NNP cord-002542-f7l4ty2j 370 18 assays assay NNS cord-002542-f7l4ty2j 370 19 . . . cord-002542-f7l4ty2j 371 1 Interestingly interestingly RB cord-002542-f7l4ty2j 371 2 however however RB cord-002542-f7l4ty2j 371 3 , , , cord-002542-f7l4ty2j 371 4 for for IN cord-002542-f7l4ty2j 371 5 the the DT cord-002542-f7l4ty2j 371 6 highest high JJS cord-002542-f7l4ty2j 371 7 particle particle NN cord-002542-f7l4ty2j 371 8 concentrations concentration NNS cord-002542-f7l4ty2j 371 9 in in IN cord-002542-f7l4ty2j 371 10 passages passage NNS cord-002542-f7l4ty2j 371 11 8 8 CD cord-002542-f7l4ty2j 371 12 and and CC cord-002542-f7l4ty2j 371 13 9 9 CD cord-002542-f7l4ty2j 371 14 , , , cord-002542-f7l4ty2j 371 15 we -PRON- PRP cord-002542-f7l4ty2j 371 16 saw see VBD cord-002542-f7l4ty2j 371 17 less less JJR cord-002542-f7l4ty2j 371 18 cell cell NN cord-002542-f7l4ty2j 371 19 death death NN cord-002542-f7l4ty2j 371 20 at at IN cord-002542-f7l4ty2j 371 21 the the DT cord-002542-f7l4ty2j 371 22 highest high JJS cord-002542-f7l4ty2j 371 23 doses dose NNS cord-002542-f7l4ty2j 371 24 ( ( -LRB- cord-002542-f7l4ty2j 371 25 300,000 300,000 CD cord-002542-f7l4ty2j 371 26 and and CC cord-002542-f7l4ty2j 371 27 30,000 30,000 CD cord-002542-f7l4ty2j 371 28 particles particle NNS cord-002542-f7l4ty2j 371 29 per per IN cord-002542-f7l4ty2j 371 30 cell cell NN cord-002542-f7l4ty2j 371 31 ) ) -RRB- cord-002542-f7l4ty2j 371 32 than than IN cord-002542-f7l4ty2j 371 33 for for IN cord-002542-f7l4ty2j 371 34 cells cell NNS cord-002542-f7l4ty2j 371 35 infected infect VBN cord-002542-f7l4ty2j 371 36 with with IN cord-002542-f7l4ty2j 371 37 the the DT cord-002542-f7l4ty2j 371 38 same same JJ cord-002542-f7l4ty2j 371 39 inoculum inoculum NN cord-002542-f7l4ty2j 371 40 ( ( -LRB- cord-002542-f7l4ty2j 371 41 and and CC cord-002542-f7l4ty2j 371 42 therefore therefore RB cord-002542-f7l4ty2j 371 43 same same JJ cord-002542-f7l4ty2j 371 44 ratio ratio NN cord-002542-f7l4ty2j 371 45 of of IN cord-002542-f7l4ty2j 371 46 full full JJ cord-002542-f7l4ty2j 371 47 - - HYPH cord-002542-f7l4ty2j 371 48 length length NN cord-002542-f7l4ty2j 371 49 to to IN cord-002542-f7l4ty2j 371 50 defective defective JJ cord-002542-f7l4ty2j 371 51 RNAs rna NNS cord-002542-f7l4ty2j 371 52 ) ) -RRB- cord-002542-f7l4ty2j 371 53 but but CC cord-002542-f7l4ty2j 371 54 at at IN cord-002542-f7l4ty2j 371 55 a a DT cord-002542-f7l4ty2j 371 56 lower low JJR cord-002542-f7l4ty2j 371 57 dose dose NN cord-002542-f7l4ty2j 371 58 ( ( -LRB- cord-002542-f7l4ty2j 371 59 3,000 3,000 CD cord-002542-f7l4ty2j 371 60 - - SYM cord-002542-f7l4ty2j 371 61 30 30 CD cord-002542-f7l4ty2j 371 62 particles particle NNS cord-002542-f7l4ty2j 371 63 per per IN cord-002542-f7l4ty2j 371 64 cell cell NN cord-002542-f7l4ty2j 371 65 ) ) -RRB- cord-002542-f7l4ty2j 371 66 . . . cord-002542-f7l4ty2j 372 1 This this DT cord-002542-f7l4ty2j 372 2 observation observation NN cord-002542-f7l4ty2j 372 3 indicates indicate VBZ cord-002542-f7l4ty2j 372 4 the the DT cord-002542-f7l4ty2j 372 5 protection protection NN cord-002542-f7l4ty2j 372 6 of of IN cord-002542-f7l4ty2j 372 7 cells cell NNS cord-002542-f7l4ty2j 372 8 from from IN cord-002542-f7l4ty2j 372 9 infection infection NN cord-002542-f7l4ty2j 372 10 and/or and/or CC cord-002542-f7l4ty2j 372 11 CPE CPE NNP cord-002542-f7l4ty2j 372 12 when when WRB cord-002542-f7l4ty2j 372 13 supplied supply VBN cord-002542-f7l4ty2j 372 14 with with IN cord-002542-f7l4ty2j 372 15 a a DT cord-002542-f7l4ty2j 372 16 large large JJ cord-002542-f7l4ty2j 372 17 dose dose NN cord-002542-f7l4ty2j 372 18 of of IN cord-002542-f7l4ty2j 372 19 viral viral JJ cord-002542-f7l4ty2j 372 20 particles particle NNS cord-002542-f7l4ty2j 372 21 that that WDT cord-002542-f7l4ty2j 372 22 contain contain VBP cord-002542-f7l4ty2j 372 23 a a DT cord-002542-f7l4ty2j 372 24 large large JJ cord-002542-f7l4ty2j 372 25 proportion proportion NN cord-002542-f7l4ty2j 372 26 of of IN cord-002542-f7l4ty2j 372 27 DI DI NNP cord-002542-f7l4ty2j 372 28 - - HYPH cord-002542-f7l4ty2j 372 29 RNAs rna NNS cord-002542-f7l4ty2j 372 30 . . . cord-002542-f7l4ty2j 373 1 In in IN cord-002542-f7l4ty2j 373 2 this this DT cord-002542-f7l4ty2j 373 3 manuscript manuscript NN cord-002542-f7l4ty2j 373 4 , , , cord-002542-f7l4ty2j 373 5 we -PRON- PRP cord-002542-f7l4ty2j 373 6 sought seek VBD cord-002542-f7l4ty2j 373 7 to to TO cord-002542-f7l4ty2j 373 8 provide provide VB cord-002542-f7l4ty2j 373 9 a a DT cord-002542-f7l4ty2j 373 10 thorough thorough JJ cord-002542-f7l4ty2j 373 11 and and CC cord-002542-f7l4ty2j 373 12 comprehensive comprehensive JJ cord-002542-f7l4ty2j 373 13 analysis analysis NN cord-002542-f7l4ty2j 373 14 of of IN cord-002542-f7l4ty2j 373 15 the the DT cord-002542-f7l4ty2j 373 16 frequency frequency NN cord-002542-f7l4ty2j 373 17 and and CC cord-002542-f7l4ty2j 373 18 identity identity NN cord-002542-f7l4ty2j 373 19 of of IN cord-002542-f7l4ty2j 373 20 recombination recombination NN cord-002542-f7l4ty2j 373 21 events event NNS cord-002542-f7l4ty2j 373 22 present present JJ cord-002542-f7l4ty2j 373 23 during during IN cord-002542-f7l4ty2j 373 24 the the DT cord-002542-f7l4ty2j 373 25 serial serial JJ cord-002542-f7l4ty2j 373 26 passaging passaging NN cord-002542-f7l4ty2j 373 27 of of IN cord-002542-f7l4ty2j 373 28 Flock Flock NNP cord-002542-f7l4ty2j 373 29 House House NNP cord-002542-f7l4ty2j 373 30 virus virus NN cord-002542-f7l4ty2j 373 31 in in IN cord-002542-f7l4ty2j 373 32 cell cell NN cord-002542-f7l4ty2j 373 33 culture culture NN cord-002542-f7l4ty2j 373 34 in in IN cord-002542-f7l4ty2j 373 35 order order NN cord-002542-f7l4ty2j 373 36 to to TO cord-002542-f7l4ty2j 373 37 elucidate elucidate VB cord-002542-f7l4ty2j 373 38 the the DT cord-002542-f7l4ty2j 373 39 pathways pathway NNS cord-002542-f7l4ty2j 373 40 and and CC cord-002542-f7l4ty2j 373 41 mechanism mechanism NN cord-002542-f7l4ty2j 373 42 of of IN cord-002542-f7l4ty2j 373 43 DI DI NNP cord-002542-f7l4ty2j 373 44 - - HYPH cord-002542-f7l4ty2j 373 45 RNA RNA NNP cord-002542-f7l4ty2j 373 46 emergence emergence NN cord-002542-f7l4ty2j 373 47 and and CC cord-002542-f7l4ty2j 373 48 evolution evolution NN cord-002542-f7l4ty2j 373 49 . . . cord-002542-f7l4ty2j 374 1 We -PRON- PRP cord-002542-f7l4ty2j 374 2 began begin VBD cord-002542-f7l4ty2j 374 3 with with IN cord-002542-f7l4ty2j 374 4 a a DT cord-002542-f7l4ty2j 374 5 homogenous homogenous JJ cord-002542-f7l4ty2j 374 6 inoculum inoculum NN cord-002542-f7l4ty2j 374 7 derived derive VBN cord-002542-f7l4ty2j 374 8 from from IN cord-002542-f7l4ty2j 374 9 plasmid plasmid NN cord-002542-f7l4ty2j 374 10 cDNAs cdna NNS cord-002542-f7l4ty2j 374 11 of of IN cord-002542-f7l4ty2j 374 12 each each DT cord-002542-f7l4ty2j 374 13 of of IN cord-002542-f7l4ty2j 374 14 the the DT cord-002542-f7l4ty2j 374 15 FHV FHV NNP cord-002542-f7l4ty2j 374 16 genomes genome NNS cord-002542-f7l4ty2j 374 17 . . . cord-002542-f7l4ty2j 375 1 In in IN cord-002542-f7l4ty2j 375 2 the the DT cord-002542-f7l4ty2j 375 3 inoculum inoculum NN cord-002542-f7l4ty2j 375 4 and and CC cord-002542-f7l4ty2j 375 5 in in IN cord-002542-f7l4ty2j 375 6 the the DT cord-002542-f7l4ty2j 375 7 early early JJ cord-002542-f7l4ty2j 375 8 passages passage NNS cord-002542-f7l4ty2j 375 9 , , , cord-002542-f7l4ty2j 375 10 we -PRON- PRP cord-002542-f7l4ty2j 375 11 find find VBP cord-002542-f7l4ty2j 375 12 a a DT cord-002542-f7l4ty2j 375 13 wide wide JJ cord-002542-f7l4ty2j 375 14 range range NN cord-002542-f7l4ty2j 375 15 of of IN cord-002542-f7l4ty2j 375 16 low low JJ cord-002542-f7l4ty2j 375 17 - - HYPH cord-002542-f7l4ty2j 375 18 frequency frequency NN cord-002542-f7l4ty2j 375 19 recombination recombination NN cord-002542-f7l4ty2j 375 20 events event NNS cord-002542-f7l4ty2j 375 21 corresponding correspond VBG cord-002542-f7l4ty2j 375 22 to to IN cord-002542-f7l4ty2j 375 23 deletions deletion NNS cord-002542-f7l4ty2j 375 24 and and CC cord-002542-f7l4ty2j 375 25 duplications duplication NNS cord-002542-f7l4ty2j 375 26 that that WDT cord-002542-f7l4ty2j 375 27 are be VBP cord-002542-f7l4ty2j 375 28 dispersed disperse VBN cord-002542-f7l4ty2j 375 29 through through IN cord-002542-f7l4ty2j 375 30 - - HYPH cord-002542-f7l4ty2j 375 31 out out NN cord-002542-f7l4ty2j 375 32 the the DT cord-002542-f7l4ty2j 375 33 viral viral JJ cord-002542-f7l4ty2j 375 34 genomic genomic JJ cord-002542-f7l4ty2j 375 35 RNAs rna NNS cord-002542-f7l4ty2j 375 36 . . . cord-002542-f7l4ty2j 376 1 We -PRON- PRP cord-002542-f7l4ty2j 376 2 can can MD cord-002542-f7l4ty2j 376 3 be be VB cord-002542-f7l4ty2j 376 4 confident confident JJ cord-002542-f7l4ty2j 376 5 that that IN cord-002542-f7l4ty2j 376 6 these these DT cord-002542-f7l4ty2j 376 7 species specie NNS cord-002542-f7l4ty2j 376 8 do do VBP cord-002542-f7l4ty2j 376 9 not not RB cord-002542-f7l4ty2j 376 10 constitute constitute VB cord-002542-f7l4ty2j 376 11 sequencing sequencing NN cord-002542-f7l4ty2j 376 12 artifacts artifact NNS cord-002542-f7l4ty2j 376 13 as as IN cord-002542-f7l4ty2j 376 14 we -PRON- PRP cord-002542-f7l4ty2j 376 15 made make VBD cord-002542-f7l4ty2j 376 16 our -PRON- PRP$ cord-002542-f7l4ty2j 376 17 RNAseq rnaseq NN cord-002542-f7l4ty2j 376 18 libraries library NNS cord-002542-f7l4ty2j 376 19 using use VBG cord-002542-f7l4ty2j 376 20 ' ' `` cord-002542-f7l4ty2j 376 21 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 376 22 ' ' '' cord-002542-f7l4ty2j 376 23 [ [ -LRB- cord-002542-f7l4ty2j 376 24 35 35 CD cord-002542-f7l4ty2j 376 25 ] ] -RRB- cord-002542-f7l4ty2j 376 26 that that WDT cord-002542-f7l4ty2j 376 27 has have VBZ cord-002542-f7l4ty2j 376 28 previously previously RB cord-002542-f7l4ty2j 376 29 been be VBN cord-002542-f7l4ty2j 376 30 demonstrated demonstrate VBN cord-002542-f7l4ty2j 376 31 to to TO cord-002542-f7l4ty2j 376 32 reduce reduce VB cord-002542-f7l4ty2j 376 33 artifactual artifactual JJ cord-002542-f7l4ty2j 376 34 recombination recombination NN cord-002542-f7l4ty2j 376 35 in in IN cord-002542-f7l4ty2j 376 36 RNAseq RNAseq NNP cord-002542-f7l4ty2j 376 37 data datum NNS cord-002542-f7l4ty2j 376 38 to to IN cord-002542-f7l4ty2j 376 39 fewer few JJR cord-002542-f7l4ty2j 376 40 than than IN cord-002542-f7l4ty2j 376 41 3 3 CD cord-002542-f7l4ty2j 376 42 events event NNS cord-002542-f7l4ty2j 376 43 per per IN cord-002542-f7l4ty2j 376 44 million million CD cord-002542-f7l4ty2j 376 45 reads read NNS cord-002542-f7l4ty2j 376 46 . . . cord-002542-f7l4ty2j 377 1 Further further JJ cord-002542-f7l4ty2j 377 2 confidence confidence NN cord-002542-f7l4ty2j 377 3 in in IN cord-002542-f7l4ty2j 377 4 the the DT cord-002542-f7l4ty2j 377 5 low low JJ cord-002542-f7l4ty2j 377 6 rates rate NNS cord-002542-f7l4ty2j 377 7 of of IN cord-002542-f7l4ty2j 377 8 artifactual artifactual JJ cord-002542-f7l4ty2j 377 9 recombination recombination NN cord-002542-f7l4ty2j 377 10 in in IN cord-002542-f7l4ty2j 377 11 our -PRON- PRP$ cord-002542-f7l4ty2j 377 12 study study NN cord-002542-f7l4ty2j 377 13 is be VBZ cord-002542-f7l4ty2j 377 14 provided provide VBN cord-002542-f7l4ty2j 377 15 internally internally RB cord-002542-f7l4ty2j 377 16 by by IN cord-002542-f7l4ty2j 377 17 inspecting inspect VBG cord-002542-f7l4ty2j 377 18 the the DT cord-002542-f7l4ty2j 377 19 numbers number NNS cord-002542-f7l4ty2j 377 20 of of IN cord-002542-f7l4ty2j 377 21 inter inter JJ cord-002542-f7l4ty2j 377 22 - - JJ cord-002542-f7l4ty2j 377 23 RNA rna JJ cord-002542-f7l4ty2j 377 24 recombination recombination NN cord-002542-f7l4ty2j 377 25 events event NNS cord-002542-f7l4ty2j 377 26 ( ( -LRB- cord-002542-f7l4ty2j 377 27 RNA1 RNA1 NNP cord-002542-f7l4ty2j 377 28 to to IN cord-002542-f7l4ty2j 377 29 RNA2 RNA2 NNP cord-002542-f7l4ty2j 377 30 and and CC cord-002542-f7l4ty2j 377 31 vice vice NN cord-002542-f7l4ty2j 377 32 versa versa RB cord-002542-f7l4ty2j 377 33 ) ) -RRB- cord-002542-f7l4ty2j 377 34 , , , cord-002542-f7l4ty2j 377 35 which which WDT cord-002542-f7l4ty2j 377 36 are be VBP cord-002542-f7l4ty2j 377 37 always always RB cord-002542-f7l4ty2j 377 38 low low JJ cord-002542-f7l4ty2j 377 39 . . . cord-002542-f7l4ty2j 378 1 Furthermore furthermore RB cord-002542-f7l4ty2j 378 2 , , , cord-002542-f7l4ty2j 378 3 the the DT cord-002542-f7l4ty2j 378 4 majority majority NN cord-002542-f7l4ty2j 378 5 of of IN cord-002542-f7l4ty2j 378 6 the the DT cord-002542-f7l4ty2j 378 7 detected detect VBN cord-002542-f7l4ty2j 378 8 inter inter JJ cord-002542-f7l4ty2j 378 9 - - JJ cord-002542-f7l4ty2j 378 10 RNA rna JJ cord-002542-f7l4ty2j 378 11 recombination recombination NN cord-002542-f7l4ty2j 378 12 events event NNS cord-002542-f7l4ty2j 378 13 correspond correspond VBP cord-002542-f7l4ty2j 378 14 to to IN cord-002542-f7l4ty2j 378 15 genomic genomic JJ cord-002542-f7l4ty2j 378 16 RNA RNA NNP cord-002542-f7l4ty2j 378 17 hetero hetero NNS cord-002542-f7l4ty2j 378 18 - - HYPH cord-002542-f7l4ty2j 378 19 and and CC cord-002542-f7l4ty2j 378 20 homo homo NN cord-002542-f7l4ty2j 378 21 - - HYPH cord-002542-f7l4ty2j 378 22 dimers dimer NNS cord-002542-f7l4ty2j 378 23 , , , cord-002542-f7l4ty2j 378 24 which which WDT cord-002542-f7l4ty2j 378 25 have have VBP cord-002542-f7l4ty2j 378 26 previously previously RB cord-002542-f7l4ty2j 378 27 been be VBN cord-002542-f7l4ty2j 378 28 characterized characterize VBN cord-002542-f7l4ty2j 378 29 as as IN cord-002542-f7l4ty2j 378 30 replication replication NN cord-002542-f7l4ty2j 378 31 intermediates intermediate NNS cord-002542-f7l4ty2j 378 32 [ [ -LRB- cord-002542-f7l4ty2j 378 33 65 65 CD cord-002542-f7l4ty2j 378 34 ] ] -RRB- cord-002542-f7l4ty2j 378 35 . . . cord-002542-f7l4ty2j 379 1 Within within IN cord-002542-f7l4ty2j 379 2 only only RB cord-002542-f7l4ty2j 379 3 2 2 CD cord-002542-f7l4ty2j 379 4 - - SYM cord-002542-f7l4ty2j 379 5 3 3 CD cord-002542-f7l4ty2j 379 6 passages passage NNS cord-002542-f7l4ty2j 379 7 , , , cord-002542-f7l4ty2j 379 8 however however RB cord-002542-f7l4ty2j 379 9 , , , cord-002542-f7l4ty2j 379 10 deletion deletion NN cord-002542-f7l4ty2j 379 11 events event NNS cord-002542-f7l4ty2j 379 12 similar similar JJ cord-002542-f7l4ty2j 379 13 to to IN cord-002542-f7l4ty2j 379 14 those those DT cord-002542-f7l4ty2j 379 15 previously previously RB cord-002542-f7l4ty2j 379 16 observed observe VBN cord-002542-f7l4ty2j 379 17 in in IN cord-002542-f7l4ty2j 379 18 DI DI NNP cord-002542-f7l4ty2j 379 19 - - HYPH cord-002542-f7l4ty2j 379 20 RNAs rna NNS cord-002542-f7l4ty2j 379 21 appear appear VBP cord-002542-f7l4ty2j 379 22 in in IN cord-002542-f7l4ty2j 379 23 all all DT cord-002542-f7l4ty2j 379 24 three three CD cord-002542-f7l4ty2j 379 25 passaging passaging NN cord-002542-f7l4ty2j 379 26 replicates replicate NNS cord-002542-f7l4ty2j 379 27 . . . cord-002542-f7l4ty2j 380 1 In in IN cord-002542-f7l4ty2j 380 2 subsequent subsequent JJ cord-002542-f7l4ty2j 380 3 passages passage NNS cord-002542-f7l4ty2j 380 4 , , , cord-002542-f7l4ty2j 380 5 these these DT cord-002542-f7l4ty2j 380 6 recombination recombination NN cord-002542-f7l4ty2j 380 7 events event NNS cord-002542-f7l4ty2j 380 8 begin begin VBP cord-002542-f7l4ty2j 380 9 to to TO cord-002542-f7l4ty2j 380 10 accumulate accumulate VB cord-002542-f7l4ty2j 380 11 rapidly rapidly RB cord-002542-f7l4ty2j 380 12 so so IN cord-002542-f7l4ty2j 380 13 as as IN cord-002542-f7l4ty2j 380 14 to to TO cord-002542-f7l4ty2j 380 15 predominate predominate VB cord-002542-f7l4ty2j 380 16 over over IN cord-002542-f7l4ty2j 380 17 full full JJ cord-002542-f7l4ty2j 380 18 - - HYPH cord-002542-f7l4ty2j 380 19 length length NN cord-002542-f7l4ty2j 380 20 viral viral JJ cord-002542-f7l4ty2j 380 21 RNAs rna NNS cord-002542-f7l4ty2j 380 22 . . . cord-002542-f7l4ty2j 381 1 This this DT cord-002542-f7l4ty2j 381 2 observation observation NN cord-002542-f7l4ty2j 381 3 of of IN cord-002542-f7l4ty2j 381 4 the the DT cord-002542-f7l4ty2j 381 5 emergence emergence NN cord-002542-f7l4ty2j 381 6 of of IN cord-002542-f7l4ty2j 381 7 DI DI NNP cord-002542-f7l4ty2j 381 8 - - HYPH cord-002542-f7l4ty2j 381 9 RNA RNA NNP cord-002542-f7l4ty2j 381 10 species specie NNS cord-002542-f7l4ty2j 381 11 , , , cord-002542-f7l4ty2j 381 12 followed follow VBN cord-002542-f7l4ty2j 381 13 by by IN cord-002542-f7l4ty2j 381 14 their -PRON- PRP$ cord-002542-f7l4ty2j 381 15 rapid rapid JJ cord-002542-f7l4ty2j 381 16 accumulation accumulation NN cord-002542-f7l4ty2j 381 17 is be VBZ cord-002542-f7l4ty2j 381 18 consistent consistent JJ cord-002542-f7l4ty2j 381 19 with with IN cord-002542-f7l4ty2j 381 20 existing exist VBG cord-002542-f7l4ty2j 381 21 theories theory NNS cord-002542-f7l4ty2j 381 22 on on IN cord-002542-f7l4ty2j 381 23 the the DT cord-002542-f7l4ty2j 381 24 evolution evolution NN cord-002542-f7l4ty2j 381 25 of of IN cord-002542-f7l4ty2j 381 26 DI DI NNP cord-002542-f7l4ty2j 381 27 - - HYPH cord-002542-f7l4ty2j 381 28 RNAs rna NNS cord-002542-f7l4ty2j 381 29 that that WDT cord-002542-f7l4ty2j 381 30 postulate postulate VBP cord-002542-f7l4ty2j 381 31 that that IN cord-002542-f7l4ty2j 381 32 a a DT cord-002542-f7l4ty2j 381 33 wide wide JJ cord-002542-f7l4ty2j 381 34 range range NN cord-002542-f7l4ty2j 381 35 of of IN cord-002542-f7l4ty2j 381 36 potential potential JJ cord-002542-f7l4ty2j 381 37 DI DI NNP cord-002542-f7l4ty2j 381 38 - - HYPH cord-002542-f7l4ty2j 381 39 RNA RNA NNP cord-002542-f7l4ty2j 381 40 species specie NNS cord-002542-f7l4ty2j 381 41 are be VBP cord-002542-f7l4ty2j 381 42 generated generate VBN cord-002542-f7l4ty2j 381 43 by by IN cord-002542-f7l4ty2j 381 44 non non JJ cord-002542-f7l4ty2j 381 45 - - JJ cord-002542-f7l4ty2j 381 46 programmed programmed JJ cord-002542-f7l4ty2j 381 47 RNA rna NN cord-002542-f7l4ty2j 381 48 recombination recombination NN cord-002542-f7l4ty2j 381 49 and and CC cord-002542-f7l4ty2j 381 50 that that IN cord-002542-f7l4ty2j 381 51 only only RB cord-002542-f7l4ty2j 381 52 a a DT cord-002542-f7l4ty2j 381 53 handful handful NN cord-002542-f7l4ty2j 381 54 are be VBP cord-002542-f7l4ty2j 381 55 successfully successfully RB cord-002542-f7l4ty2j 381 56 replicated replicate VBN cord-002542-f7l4ty2j 381 57 and and CC cord-002542-f7l4ty2j 381 58 thus thus RB cord-002542-f7l4ty2j 381 59 accumulate accumulate VB cord-002542-f7l4ty2j 381 60 [ [ -LRB- cord-002542-f7l4ty2j 381 61 9 9 CD cord-002542-f7l4ty2j 381 62 ] ] -RRB- cord-002542-f7l4ty2j 381 63 . . . cord-002542-f7l4ty2j 382 1 While while IN cord-002542-f7l4ty2j 382 2 the the DT cord-002542-f7l4ty2j 382 3 short short RB cord-002542-f7l4ty2j 382 4 - - HYPH cord-002542-f7l4ty2j 382 5 read read NN cord-002542-f7l4ty2j 382 6 data datum NNS cord-002542-f7l4ty2j 382 7 provide provide VBP cord-002542-f7l4ty2j 382 8 high high JJ cord-002542-f7l4ty2j 382 9 - - HYPH cord-002542-f7l4ty2j 382 10 resolution resolution NN cord-002542-f7l4ty2j 382 11 characterization characterization NN cord-002542-f7l4ty2j 382 12 of of IN cord-002542-f7l4ty2j 382 13 individual individual JJ cord-002542-f7l4ty2j 382 14 recombination recombination NN cord-002542-f7l4ty2j 382 15 events event NNS cord-002542-f7l4ty2j 382 16 , , , cord-002542-f7l4ty2j 382 17 it -PRON- PRP cord-002542-f7l4ty2j 382 18 is be VBZ cord-002542-f7l4ty2j 382 19 through through IN cord-002542-f7l4ty2j 382 20 the the DT cord-002542-f7l4ty2j 382 21 use use NN cord-002542-f7l4ty2j 382 22 of of IN cord-002542-f7l4ty2j 382 23 the the DT cord-002542-f7l4ty2j 382 24 Oxford Oxford NNP cord-002542-f7l4ty2j 382 25 Nanopore Nanopore NNP cord-002542-f7l4ty2j 382 26 Technologies Technologies NNP cord-002542-f7l4ty2j 382 27 ( ( -LRB- cord-002542-f7l4ty2j 382 28 ONT ONT NNP cord-002542-f7l4ty2j 382 29 ) ) -RRB- cord-002542-f7l4ty2j 382 30 MinION minion FW cord-002542-f7l4ty2j 382 31 that that IN cord-002542-f7l4ty2j 382 32 we -PRON- PRP cord-002542-f7l4ty2j 382 33 are be VBP cord-002542-f7l4ty2j 382 34 able able JJ cord-002542-f7l4ty2j 382 35 reconstitute reconstitute VB cord-002542-f7l4ty2j 382 36 the the DT cord-002542-f7l4ty2j 382 37 complex complex JJ cord-002542-f7l4ty2j 382 38 full full JJ cord-002542-f7l4ty2j 382 39 - - HYPH cord-002542-f7l4ty2j 382 40 length length NN cord-002542-f7l4ty2j 382 41 genomic genomic JJ cord-002542-f7l4ty2j 382 42 landscape landscape NN cord-002542-f7l4ty2j 382 43 of of IN cord-002542-f7l4ty2j 382 44 FHV FHV NNP cord-002542-f7l4ty2j 382 45 during during IN cord-002542-f7l4ty2j 382 46 passaging passaging NN cord-002542-f7l4ty2j 382 47 and and CC cord-002542-f7l4ty2j 382 48 determine determine VB cord-002542-f7l4ty2j 382 49 the the DT cord-002542-f7l4ty2j 382 50 relative relative JJ cord-002542-f7l4ty2j 382 51 abundances abundance NNS cord-002542-f7l4ty2j 382 52 of of IN cord-002542-f7l4ty2j 382 53 the the DT cord-002542-f7l4ty2j 382 54 genomic genomic JJ cord-002542-f7l4ty2j 382 55 RNAs rna NNS cord-002542-f7l4ty2j 382 56 in in IN cord-002542-f7l4ty2j 382 57 each each DT cord-002542-f7l4ty2j 382 58 passage passage NN cord-002542-f7l4ty2j 382 59 . . . cord-002542-f7l4ty2j 383 1 As as IN cord-002542-f7l4ty2j 383 2 a a DT cord-002542-f7l4ty2j 383 3 result result NN cord-002542-f7l4ty2j 383 4 , , , cord-002542-f7l4ty2j 383 5 we -PRON- PRP cord-002542-f7l4ty2j 383 6 were be VBD cord-002542-f7l4ty2j 383 7 able able JJ cord-002542-f7l4ty2j 383 8 to to TO cord-002542-f7l4ty2j 383 9 determine determine VB cord-002542-f7l4ty2j 383 10 that that DT cord-002542-f7l4ty2j 383 11 by by IN cord-002542-f7l4ty2j 383 12 the the DT cord-002542-f7l4ty2j 383 13 final final JJ cord-002542-f7l4ty2j 383 14 passage passage NN cord-002542-f7l4ty2j 384 1 only~2 only~2 NNP cord-002542-f7l4ty2j 385 1 % % NN cord-002542-f7l4ty2j 385 2 of of IN cord-002542-f7l4ty2j 385 3 the the DT cord-002542-f7l4ty2j 385 4 mapped map VBN cord-002542-f7l4ty2j 385 5 reads read NNS cord-002542-f7l4ty2j 385 6 are be VBP cord-002542-f7l4ty2j 385 7 full full JJ cord-002542-f7l4ty2j 385 8 - - HYPH cord-002542-f7l4ty2j 385 9 length length NN cord-002542-f7l4ty2j 385 10 viral viral JJ cord-002542-f7l4ty2j 385 11 RNA1 RNA1 NNP cord-002542-f7l4ty2j 385 12 , , , cord-002542-f7l4ty2j 385 13 which which WDT cord-002542-f7l4ty2j 385 14 corresponded correspond VBD cord-002542-f7l4ty2j 385 15 with with IN cord-002542-f7l4ty2j 385 16 a a DT cord-002542-f7l4ty2j 385 17 large large JJ cord-002542-f7l4ty2j 385 18 reduction reduction NN cord-002542-f7l4ty2j 385 19 in in IN cord-002542-f7l4ty2j 385 20 specific specific JJ cord-002542-f7l4ty2j 385 21 infectivity infectivity NN cord-002542-f7l4ty2j 385 22 . . . cord-002542-f7l4ty2j 386 1 Additionally additionally RB cord-002542-f7l4ty2j 386 2 , , , cord-002542-f7l4ty2j 386 3 the the DT cord-002542-f7l4ty2j 386 4 nanopore nanopore NNP cord-002542-f7l4ty2j 386 5 data datum NNS cord-002542-f7l4ty2j 386 6 revealed reveal VBD cord-002542-f7l4ty2j 386 7 complex complex JJ cord-002542-f7l4ty2j 386 8 rearrangements rearrangement NNS cord-002542-f7l4ty2j 386 9 of of IN cord-002542-f7l4ty2j 386 10 RNA RNA NNP cord-002542-f7l4ty2j 386 11 genomes genome NNS cord-002542-f7l4ty2j 386 12 , , , cord-002542-f7l4ty2j 386 13 including include VBG cord-002542-f7l4ty2j 386 14 the the DT cord-002542-f7l4ty2j 386 15 excision excision NN cord-002542-f7l4ty2j 386 16 of of IN cord-002542-f7l4ty2j 386 17 an an DT cord-002542-f7l4ty2j 386 18 entire entire JJ cord-002542-f7l4ty2j 386 19 functional functional JJ cord-002542-f7l4ty2j 386 20 RNA RNA NNP cord-002542-f7l4ty2j 386 21 motif motif NN cord-002542-f7l4ty2j 386 22 and and CC cord-002542-f7l4ty2j 386 23 its -PRON- PRP$ cord-002542-f7l4ty2j 386 24 reinsertion reinsertion NN cord-002542-f7l4ty2j 386 25 in in IN cord-002542-f7l4ty2j 386 26 the the DT cord-002542-f7l4ty2j 386 27 5'UTR 5'utr CD cord-002542-f7l4ty2j 386 28 of of IN cord-002542-f7l4ty2j 386 29 RNA1 RNA1 NNP cord-002542-f7l4ty2j 386 30 . . . cord-002542-f7l4ty2j 387 1 The the DT cord-002542-f7l4ty2j 387 2 variation variation NN cord-002542-f7l4ty2j 387 3 in in IN cord-002542-f7l4ty2j 387 4 recombination recombination NN cord-002542-f7l4ty2j 387 5 boundaries boundary NNS cord-002542-f7l4ty2j 387 6 of of IN cord-002542-f7l4ty2j 387 7 the the DT cord-002542-f7l4ty2j 387 8 DI DI NNP cord-002542-f7l4ty2j 387 9 - - HYPH cord-002542-f7l4ty2j 387 10 RNAs RNAs NNP cord-002542-f7l4ty2j 387 11 suggests suggest VBZ cord-002542-f7l4ty2j 387 12 that that IN cord-002542-f7l4ty2j 387 13 a a DT cord-002542-f7l4ty2j 387 14 range range NN cord-002542-f7l4ty2j 387 15 of of IN cord-002542-f7l4ty2j 387 16 deletions deletion NNS cord-002542-f7l4ty2j 387 17 can can MD cord-002542-f7l4ty2j 387 18 be be VB cord-002542-f7l4ty2j 387 19 tolerated tolerate VBN cord-002542-f7l4ty2j 387 20 . . . cord-002542-f7l4ty2j 388 1 However however RB cord-002542-f7l4ty2j 388 2 , , , cord-002542-f7l4ty2j 388 3 it -PRON- PRP cord-002542-f7l4ty2j 388 4 is be VBZ cord-002542-f7l4ty2j 388 5 important important JJ cord-002542-f7l4ty2j 388 6 to to TO cord-002542-f7l4ty2j 388 7 note note VB cord-002542-f7l4ty2j 388 8 that that IN cord-002542-f7l4ty2j 388 9 while while IN cord-002542-f7l4ty2j 388 10 each each DT cord-002542-f7l4ty2j 388 11 replicate replicate VBP cord-002542-f7l4ty2j 388 12 is be VBZ cord-002542-f7l4ty2j 388 13 its -PRON- PRP$ cord-002542-f7l4ty2j 388 14 own own JJ cord-002542-f7l4ty2j 388 15 distinct distinct JJ cord-002542-f7l4ty2j 388 16 lineage lineage NN cord-002542-f7l4ty2j 388 17 , , , cord-002542-f7l4ty2j 388 18 each each DT cord-002542-f7l4ty2j 388 19 replicate replicate VBP cord-002542-f7l4ty2j 388 20 passaging passaging NN cord-002542-f7l4ty2j 388 21 experiment experiment NN cord-002542-f7l4ty2j 388 22 was be VBD cord-002542-f7l4ty2j 388 23 derived derive VBN cord-002542-f7l4ty2j 388 24 from from IN cord-002542-f7l4ty2j 388 25 the the DT cord-002542-f7l4ty2j 388 26 same same JJ cord-002542-f7l4ty2j 388 27 initial initial JJ cord-002542-f7l4ty2j 388 28 inoculum inoculum NN cord-002542-f7l4ty2j 388 29 . . . cord-002542-f7l4ty2j 389 1 We -PRON- PRP cord-002542-f7l4ty2j 389 2 chose choose VBD cord-002542-f7l4ty2j 389 3 to to TO cord-002542-f7l4ty2j 389 4 design design VB cord-002542-f7l4ty2j 389 5 the the DT cord-002542-f7l4ty2j 389 6 experiment experiment NN cord-002542-f7l4ty2j 389 7 this this DT cord-002542-f7l4ty2j 389 8 way way NN cord-002542-f7l4ty2j 389 9 to to TO cord-002542-f7l4ty2j 389 10 determine determine VB cord-002542-f7l4ty2j 389 11 if if IN cord-002542-f7l4ty2j 389 12 the the DT cord-002542-f7l4ty2j 389 13 same same JJ cord-002542-f7l4ty2j 389 14 DI DI NNP cord-002542-f7l4ty2j 389 15 - - HYPH cord-002542-f7l4ty2j 389 16 RNAs rna NNS cord-002542-f7l4ty2j 389 17 would would MD cord-002542-f7l4ty2j 389 18 be be VB cord-002542-f7l4ty2j 389 19 generated generate VBN cord-002542-f7l4ty2j 389 20 independently independently RB cord-002542-f7l4ty2j 389 21 or or CC cord-002542-f7l4ty2j 389 22 if if IN cord-002542-f7l4ty2j 389 23 completely completely RB cord-002542-f7l4ty2j 389 24 different different JJ cord-002542-f7l4ty2j 389 25 deletions deletion NNS cord-002542-f7l4ty2j 389 26 would would MD cord-002542-f7l4ty2j 389 27 arise arise VB cord-002542-f7l4ty2j 389 28 and and CC cord-002542-f7l4ty2j 389 29 be be VB cord-002542-f7l4ty2j 389 30 selected select VBN cord-002542-f7l4ty2j 389 31 for for IN cord-002542-f7l4ty2j 389 32 even even RB cord-002542-f7l4ty2j 389 33 though though IN cord-002542-f7l4ty2j 389 34 the the DT cord-002542-f7l4ty2j 389 35 environmental environmental JJ cord-002542-f7l4ty2j 389 36 conditions condition NNS cord-002542-f7l4ty2j 389 37 are be VBP cord-002542-f7l4ty2j 389 38 practically practically RB cord-002542-f7l4ty2j 389 39 the the DT cord-002542-f7l4ty2j 389 40 same same JJ cord-002542-f7l4ty2j 389 41 . . . cord-002542-f7l4ty2j 390 1 Here here RB cord-002542-f7l4ty2j 390 2 , , , cord-002542-f7l4ty2j 390 3 we -PRON- PRP cord-002542-f7l4ty2j 390 4 observe observe VBP cord-002542-f7l4ty2j 390 5 the the DT cord-002542-f7l4ty2j 390 6 latter latter JJ cord-002542-f7l4ty2j 390 7 ( ( -LRB- cord-002542-f7l4ty2j 390 8 Table table NN cord-002542-f7l4ty2j 390 9 2 2 CD cord-002542-f7l4ty2j 390 10 ) ) -RRB- cord-002542-f7l4ty2j 390 11 . . . cord-002542-f7l4ty2j 391 1 Few few JJ cord-002542-f7l4ty2j 391 2 of of IN cord-002542-f7l4ty2j 391 3 the the DT cord-002542-f7l4ty2j 391 4 RNA1 RNA1 NNP cord-002542-f7l4ty2j 391 5 recombination recombination NN cord-002542-f7l4ty2j 391 6 events event NNS cord-002542-f7l4ty2j 391 7 observed observe VBN cord-002542-f7l4ty2j 391 8 in in IN cord-002542-f7l4ty2j 391 9 the the DT cord-002542-f7l4ty2j 391 10 inoculum inoculum NN cord-002542-f7l4ty2j 391 11 are be VBP cord-002542-f7l4ty2j 391 12 observed observe VBN cord-002542-f7l4ty2j 391 13 again again RB cord-002542-f7l4ty2j 391 14 in in IN cord-002542-f7l4ty2j 391 15 subsequent subsequent JJ cord-002542-f7l4ty2j 391 16 passages passage NNS cord-002542-f7l4ty2j 391 17 . . . cord-002542-f7l4ty2j 392 1 Additionally additionally RB cord-002542-f7l4ty2j 392 2 , , , cord-002542-f7l4ty2j 392 3 even even RB cord-002542-f7l4ty2j 392 4 though though IN cord-002542-f7l4ty2j 392 5 we -PRON- PRP cord-002542-f7l4ty2j 392 6 found find VBD cord-002542-f7l4ty2j 392 7 the the DT cord-002542-f7l4ty2j 392 8 event event NN cord-002542-f7l4ty2j 392 9 ' ' '' cord-002542-f7l4ty2j 392 10 738 738 CD cord-002542-f7l4ty2j 392 11 ^ ^ SYM cord-002542-f7l4ty2j 392 12 1219 1219 CD cord-002542-f7l4ty2j 392 13 ' ' '' cord-002542-f7l4ty2j 392 14 in in IN cord-002542-f7l4ty2j 392 15 RNA2 RNA2 NNP cord-002542-f7l4ty2j 393 1 the the DT cord-002542-f7l4ty2j 393 2 inoculum inoculum NN cord-002542-f7l4ty2j 393 3 , , , cord-002542-f7l4ty2j 393 4 this this DT cord-002542-f7l4ty2j 393 5 was be VBD cord-002542-f7l4ty2j 393 6 not not RB cord-002542-f7l4ty2j 393 7 the the DT cord-002542-f7l4ty2j 393 8 final final JJ cord-002542-f7l4ty2j 393 9 predominant predominant JJ cord-002542-f7l4ty2j 393 10 species specie NNS cord-002542-f7l4ty2j 393 11 in in IN cord-002542-f7l4ty2j 393 12 any any DT cord-002542-f7l4ty2j 393 13 replicate replicate NN cord-002542-f7l4ty2j 393 14 . . . cord-002542-f7l4ty2j 394 1 Therefore therefore RB cord-002542-f7l4ty2j 394 2 , , , cord-002542-f7l4ty2j 394 3 the the DT cord-002542-f7l4ty2j 394 4 evolution evolution NN cord-002542-f7l4ty2j 394 5 of of IN cord-002542-f7l4ty2j 394 6 DI DI NNP cord-002542-f7l4ty2j 394 7 - - HYPH cord-002542-f7l4ty2j 394 8 RNAs RNAs NNPS cord-002542-f7l4ty2j 394 9 was be VBD cord-002542-f7l4ty2j 394 10 not not RB cord-002542-f7l4ty2j 394 11 pre pre JJ cord-002542-f7l4ty2j 394 12 - - JJ cord-002542-f7l4ty2j 394 13 determined determined JJ cord-002542-f7l4ty2j 395 1 by by IN cord-002542-f7l4ty2j 395 2 the the DT cord-002542-f7l4ty2j 395 3 presence presence NN cord-002542-f7l4ty2j 395 4 of of IN cord-002542-f7l4ty2j 395 5 rare rare JJ cord-002542-f7l4ty2j 395 6 DI DI NNP cord-002542-f7l4ty2j 395 7 - - HYPH cord-002542-f7l4ty2j 395 8 RNA RNA NNP cord-002542-f7l4ty2j 395 9 species specie NNS cord-002542-f7l4ty2j 395 10 in in IN cord-002542-f7l4ty2j 395 11 the the DT cord-002542-f7l4ty2j 395 12 common common JJ cord-002542-f7l4ty2j 395 13 inoculum inoculum NN cord-002542-f7l4ty2j 395 14 ( ( -LRB- cord-002542-f7l4ty2j 395 15 a a DT cord-002542-f7l4ty2j 395 16 founder founder NN cord-002542-f7l4ty2j 395 17 - - HYPH cord-002542-f7l4ty2j 395 18 effect effect NN cord-002542-f7l4ty2j 395 19 ) ) -RRB- cord-002542-f7l4ty2j 395 20 , , , cord-002542-f7l4ty2j 395 21 but but CC cord-002542-f7l4ty2j 395 22 rather rather RB cord-002542-f7l4ty2j 395 23 by by IN cord-002542-f7l4ty2j 395 24 the the DT cord-002542-f7l4ty2j 395 25 selection selection NN cord-002542-f7l4ty2j 395 26 of of IN cord-002542-f7l4ty2j 395 27 well well RB cord-002542-f7l4ty2j 395 28 - - HYPH cord-002542-f7l4ty2j 395 29 replicating replicate VBG cord-002542-f7l4ty2j 395 30 DI DI NNP cord-002542-f7l4ty2j 395 31 - - HYPH cord-002542-f7l4ty2j 395 32 R R NNP cord-002542-f7l4ty2j 395 33 - - HYPH cord-002542-f7l4ty2j 395 34 NAs NAs NNPS cord-002542-f7l4ty2j 395 35 that that WDT cord-002542-f7l4ty2j 395 36 arose arise VBD cord-002542-f7l4ty2j 395 37 later later RB cord-002542-f7l4ty2j 395 38 during during IN cord-002542-f7l4ty2j 395 39 serial serial JJ cord-002542-f7l4ty2j 395 40 passaging passaging NN cord-002542-f7l4ty2j 395 41 . . . cord-002542-f7l4ty2j 396 1 Nonetheless nonetheless RB cord-002542-f7l4ty2j 396 2 , , , cord-002542-f7l4ty2j 396 3 the the DT cord-002542-f7l4ty2j 396 4 final final JJ cord-002542-f7l4ty2j 396 5 recombination recombination NN cord-002542-f7l4ty2j 396 6 events event NNS cord-002542-f7l4ty2j 396 7 are be VBP cord-002542-f7l4ty2j 396 8 highly highly RB cord-002542-f7l4ty2j 396 9 similar similar JJ cord-002542-f7l4ty2j 396 10 between between IN cord-002542-f7l4ty2j 396 11 replicates replicate NNS cord-002542-f7l4ty2j 396 12 and and CC cord-002542-f7l4ty2j 396 13 to to IN cord-002542-f7l4ty2j 396 14 previous previous JJ cord-002542-f7l4ty2j 396 15 reports report NNS cord-002542-f7l4ty2j 396 16 from from IN cord-002542-f7l4ty2j 396 17 different different JJ cord-002542-f7l4ty2j 396 18 laboratories laboratory NNS cord-002542-f7l4ty2j 396 19 . . . cord-002542-f7l4ty2j 397 1 Therefore therefore RB cord-002542-f7l4ty2j 397 2 , , , cord-002542-f7l4ty2j 397 3 this this DT cord-002542-f7l4ty2j 397 4 indicates indicate VBZ cord-002542-f7l4ty2j 397 5 that that IN cord-002542-f7l4ty2j 397 6 either either CC cord-002542-f7l4ty2j 397 7 the the DT cord-002542-f7l4ty2j 397 8 DI DI NNP cord-002542-f7l4ty2j 397 9 - - HYPH cord-002542-f7l4ty2j 397 10 RNAs rna NNS cord-002542-f7l4ty2j 397 11 have have VBP cord-002542-f7l4ty2j 397 12 emerged emerge VBN cord-002542-f7l4ty2j 397 13 due due IN cord-002542-f7l4ty2j 397 14 to to IN cord-002542-f7l4ty2j 397 15 a a DT cord-002542-f7l4ty2j 397 16 common common JJ cord-002542-f7l4ty2j 397 17 mechanism mechanism NN cord-002542-f7l4ty2j 397 18 of of IN cord-002542-f7l4ty2j 397 19 formation formation NN cord-002542-f7l4ty2j 397 20 , , , cord-002542-f7l4ty2j 397 21 the the DT cord-002542-f7l4ty2j 397 22 presence presence NN cord-002542-f7l4ty2j 397 23 of of IN cord-002542-f7l4ty2j 397 24 a a DT cord-002542-f7l4ty2j 397 25 common common JJ cord-002542-f7l4ty2j 397 26 selectivity selectivity NN cord-002542-f7l4ty2j 397 27 filter filter NN cord-002542-f7l4ty2j 397 28 , , , cord-002542-f7l4ty2j 397 29 or or CC cord-002542-f7l4ty2j 397 30 both both DT cord-002542-f7l4ty2j 397 31 . . . cord-002542-f7l4ty2j 398 1 In in IN cord-002542-f7l4ty2j 398 2 addition addition NN cord-002542-f7l4ty2j 398 3 to to IN cord-002542-f7l4ty2j 398 4 providing provide VBG cord-002542-f7l4ty2j 398 5 a a DT cord-002542-f7l4ty2j 398 6 thorough thorough JJ cord-002542-f7l4ty2j 398 7 analysis analysis NN cord-002542-f7l4ty2j 398 8 of of IN cord-002542-f7l4ty2j 398 9 the the DT cord-002542-f7l4ty2j 398 10 pathways pathway NNS cord-002542-f7l4ty2j 398 11 of of IN cord-002542-f7l4ty2j 398 12 defective defective JJ cord-002542-f7l4ty2j 398 13 RNA RNA NNP cord-002542-f7l4ty2j 398 14 formation formation NN cord-002542-f7l4ty2j 398 15 and and CC cord-002542-f7l4ty2j 398 16 evolution evolution NN cord-002542-f7l4ty2j 398 17 , , , cord-002542-f7l4ty2j 398 18 there there EX cord-002542-f7l4ty2j 398 19 are be VBP cord-002542-f7l4ty2j 398 20 two two CD cord-002542-f7l4ty2j 398 21 unexpected unexpected JJ cord-002542-f7l4ty2j 398 22 and and CC cord-002542-f7l4ty2j 398 23 critical critical JJ cord-002542-f7l4ty2j 398 24 observations observation NNS cord-002542-f7l4ty2j 398 25 made make VBN cord-002542-f7l4ty2j 398 26 through through IN cord-002542-f7l4ty2j 398 27 this this DT cord-002542-f7l4ty2j 398 28 study study NN cord-002542-f7l4ty2j 398 29 . . . cord-002542-f7l4ty2j 399 1 First first RB cord-002542-f7l4ty2j 399 2 : : : cord-002542-f7l4ty2j 399 3 while while IN cord-002542-f7l4ty2j 399 4 we -PRON- PRP cord-002542-f7l4ty2j 399 5 observe observe VBP cord-002542-f7l4ty2j 399 6 a a DT cord-002542-f7l4ty2j 399 7 wide wide JJ cord-002542-f7l4ty2j 399 8 range range NN cord-002542-f7l4ty2j 399 9 of of IN cord-002542-f7l4ty2j 399 10 recombination recombination NN cord-002542-f7l4ty2j 399 11 events event NNS cord-002542-f7l4ty2j 399 12 early early RB cord-002542-f7l4ty2j 399 13 on on RB cord-002542-f7l4ty2j 399 14 during during IN cord-002542-f7l4ty2j 399 15 passaging passaging NN cord-002542-f7l4ty2j 399 16 , , , cord-002542-f7l4ty2j 399 17 only only RB cord-002542-f7l4ty2j 399 18 a a DT cord-002542-f7l4ty2j 399 19 limited limited JJ cord-002542-f7l4ty2j 399 20 number number NN cord-002542-f7l4ty2j 399 21 of of IN cord-002542-f7l4ty2j 399 22 events event NNS cord-002542-f7l4ty2j 399 23 are be VBP cord-002542-f7l4ty2j 399 24 subsequently subsequently RB cord-002542-f7l4ty2j 399 25 amplified amplify VBN cord-002542-f7l4ty2j 399 26 and and CC cord-002542-f7l4ty2j 399 27 later later RB cord-002542-f7l4ty2j 399 28 define define VB cord-002542-f7l4ty2j 399 29 DI DI NNP cord-002542-f7l4ty2j 399 30 - - HYPH cord-002542-f7l4ty2j 399 31 RNAs rna NNS cord-002542-f7l4ty2j 399 32 . . . cord-002542-f7l4ty2j 400 1 Moreover moreover RB cord-002542-f7l4ty2j 400 2 , , , cord-002542-f7l4ty2j 400 3 these these DT cord-002542-f7l4ty2j 400 4 limited limited JJ cord-002542-f7l4ty2j 400 5 sets set NNS cord-002542-f7l4ty2j 400 6 of of IN cord-002542-f7l4ty2j 400 7 events event NNS cord-002542-f7l4ty2j 400 8 are be VBP cord-002542-f7l4ty2j 400 9 similar similar JJ cord-002542-f7l4ty2j 400 10 between between IN cord-002542-f7l4ty2j 400 11 replicates replicate NNS cord-002542-f7l4ty2j 400 12 , , , cord-002542-f7l4ty2j 400 13 and and CC cord-002542-f7l4ty2j 400 14 to to IN cord-002542-f7l4ty2j 400 15 previous previous JJ cord-002542-f7l4ty2j 400 16 studies study NNS cord-002542-f7l4ty2j 400 17 . . . cord-002542-f7l4ty2j 401 1 This this DT cord-002542-f7l4ty2j 401 2 suggests suggest VBZ cord-002542-f7l4ty2j 401 3 that that IN cord-002542-f7l4ty2j 401 4 while while IN cord-002542-f7l4ty2j 401 5 a a DT cord-002542-f7l4ty2j 401 6 large large JJ cord-002542-f7l4ty2j 401 7 pool pool NN cord-002542-f7l4ty2j 401 8 of of IN cord-002542-f7l4ty2j 401 9 potential potential JJ cord-002542-f7l4ty2j 401 10 defective defective JJ cord-002542-f7l4ty2j 401 11 RNAs rna NNS cord-002542-f7l4ty2j 401 12 are be VBP cord-002542-f7l4ty2j 401 13 generated generate VBN cord-002542-f7l4ty2j 401 14 , , , cord-002542-f7l4ty2j 401 15 only only RB cord-002542-f7l4ty2j 401 16 a a DT cord-002542-f7l4ty2j 401 17 small small JJ cord-002542-f7l4ty2j 401 18 number number NN cord-002542-f7l4ty2j 401 19 are be VBP cord-002542-f7l4ty2j 401 20 capable capable JJ cord-002542-f7l4ty2j 401 21 of of IN cord-002542-f7l4ty2j 401 22 accumulating accumulate VBG cord-002542-f7l4ty2j 401 23 . . . cord-002542-f7l4ty2j 402 1 Secondly secondly RB cord-002542-f7l4ty2j 402 2 : : : cord-002542-f7l4ty2j 402 3 we -PRON- PRP cord-002542-f7l4ty2j 402 4 do do VBP cord-002542-f7l4ty2j 402 5 not not RB cord-002542-f7l4ty2j 402 6 observe observe VB cord-002542-f7l4ty2j 402 7 the the DT cord-002542-f7l4ty2j 402 8 amplification amplification NN cord-002542-f7l4ty2j 402 9 of of IN cord-002542-f7l4ty2j 402 10 DI DI NNP cord-002542-f7l4ty2j 402 11 - - HYPH cord-002542-f7l4ty2j 402 12 RNAs rna NNS cord-002542-f7l4ty2j 402 13 with with IN cord-002542-f7l4ty2j 402 14 only only RB cord-002542-f7l4ty2j 402 15 one one CD cord-002542-f7l4ty2j 402 16 deletion deletion NN cord-002542-f7l4ty2j 402 17 . . . cord-002542-f7l4ty2j 403 1 In in IN cord-002542-f7l4ty2j 403 2 contrast contrast NN cord-002542-f7l4ty2j 403 3 , , , cord-002542-f7l4ty2j 403 4 ' ' `` cord-002542-f7l4ty2j 403 5 mature mature VB cord-002542-f7l4ty2j 403 6 ' ' '' cord-002542-f7l4ty2j 403 7 DI di NN cord-002542-f7l4ty2j 403 8 - - HYPH cord-002542-f7l4ty2j 403 9 RNAs rna NNS cord-002542-f7l4ty2j 403 10 accumulate accumulate VBP cord-002542-f7l4ty2j 403 11 rapidly rapidly RB cord-002542-f7l4ty2j 403 12 . . . cord-002542-f7l4ty2j 404 1 Nonetheless nonetheless RB cord-002542-f7l4ty2j 404 2 , , , cord-002542-f7l4ty2j 404 3 we -PRON- PRP cord-002542-f7l4ty2j 404 4 do do VBP cord-002542-f7l4ty2j 404 5 find find VB cord-002542-f7l4ty2j 404 6 evidence evidence NN cord-002542-f7l4ty2j 404 7 for for IN cord-002542-f7l4ty2j 404 8 intermediate intermediate JJ cord-002542-f7l4ty2j 404 9 DI DI NNP cord-002542-f7l4ty2j 404 10 - - HYPH cord-002542-f7l4ty2j 404 11 RNAs rna NNS cord-002542-f7l4ty2j 404 12 as as RB cord-002542-f7l4ty2j 404 13 early early RB cord-002542-f7l4ty2j 404 14 as as IN cord-002542-f7l4ty2j 404 15 the the DT cord-002542-f7l4ty2j 404 16 inoculum inoculum NN cord-002542-f7l4ty2j 404 17 sample sample NN cord-002542-f7l4ty2j 404 18 . . . cord-002542-f7l4ty2j 405 1 This this DT cord-002542-f7l4ty2j 405 2 indicates indicate VBZ cord-002542-f7l4ty2j 405 3 that that IN cord-002542-f7l4ty2j 405 4 intermediate intermediate JJ cord-002542-f7l4ty2j 405 5 defective defective JJ cord-002542-f7l4ty2j 405 6 - - HYPH cord-002542-f7l4ty2j 405 7 species specie NNS cord-002542-f7l4ty2j 405 8 are be VBP cord-002542-f7l4ty2j 405 9 either either CC cord-002542-f7l4ty2j 405 10 non non JJ cord-002542-f7l4ty2j 405 11 - - JJ cord-002542-f7l4ty2j 405 12 competitive competitive JJ cord-002542-f7l4ty2j 405 13 and and CC cord-002542-f7l4ty2j 405 14 do do VBP cord-002542-f7l4ty2j 405 15 not not RB cord-002542-f7l4ty2j 405 16 accumulate accumulate VB cord-002542-f7l4ty2j 405 17 or or CC cord-002542-f7l4ty2j 405 18 are be VBP cord-002542-f7l4ty2j 405 19 not not RB cord-002542-f7l4ty2j 405 20 formed form VBN cord-002542-f7l4ty2j 405 21 as as IN cord-002542-f7l4ty2j 405 22 a a DT cord-002542-f7l4ty2j 405 23 pre pre NN cord-002542-f7l4ty2j 405 24 - - NN cord-002542-f7l4ty2j 405 25 cursor cursor NN cord-002542-f7l4ty2j 405 26 to to IN cord-002542-f7l4ty2j 405 27 mature mature VB cord-002542-f7l4ty2j 405 28 DI DI NNP cord-002542-f7l4ty2j 405 29 - - HYPH cord-002542-f7l4ty2j 405 30 RNAs rna NNS cord-002542-f7l4ty2j 405 31 . . . cord-002542-f7l4ty2j 406 1 These these DT cord-002542-f7l4ty2j 406 2 two two CD cord-002542-f7l4ty2j 406 3 observations observation NNS cord-002542-f7l4ty2j 406 4 provide provide VBP cord-002542-f7l4ty2j 406 5 important important JJ cord-002542-f7l4ty2j 406 6 insights insight NNS cord-002542-f7l4ty2j 406 7 into into IN cord-002542-f7l4ty2j 406 8 the the DT cord-002542-f7l4ty2j 406 9 potential potential JJ cord-002542-f7l4ty2j 406 10 mechanisms mechanism NNS cord-002542-f7l4ty2j 406 11 of of IN cord-002542-f7l4ty2j 406 12 DI DI NNP cord-002542-f7l4ty2j 406 13 - - HYPH cord-002542-f7l4ty2j 406 14 RNA RNA NNP cord-002542-f7l4ty2j 406 15 emergence emergence NN cord-002542-f7l4ty2j 406 16 and and CC cord-002542-f7l4ty2j 406 17 evolution evolution NN cord-002542-f7l4ty2j 406 18 . . . cord-002542-f7l4ty2j 407 1 While while IN cord-002542-f7l4ty2j 407 2 there there EX cord-002542-f7l4ty2j 407 3 is be VBZ cord-002542-f7l4ty2j 407 4 a a DT cord-002542-f7l4ty2j 407 5 strong strong JJ cord-002542-f7l4ty2j 407 6 selection selection NN cord-002542-f7l4ty2j 407 7 pressure pressure NN cord-002542-f7l4ty2j 407 8 for for IN cord-002542-f7l4ty2j 407 9 DI DI NNP cord-002542-f7l4ty2j 407 10 - - HYPH cord-002542-f7l4ty2j 407 11 RNAs rna NNS cord-002542-f7l4ty2j 407 12 to to TO cord-002542-f7l4ty2j 407 13 retain retain VB cord-002542-f7l4ty2j 407 14 essential essential JJ cord-002542-f7l4ty2j 407 15 functional functional JJ cord-002542-f7l4ty2j 407 16 genomic genomic JJ cord-002542-f7l4ty2j 407 17 elements element NNS cord-002542-f7l4ty2j 407 18 , , , cord-002542-f7l4ty2j 407 19 it -PRON- PRP cord-002542-f7l4ty2j 407 20 is be VBZ cord-002542-f7l4ty2j 407 21 also also RB cord-002542-f7l4ty2j 407 22 postulated postulate VBN cord-002542-f7l4ty2j 407 23 that that IN cord-002542-f7l4ty2j 407 24 a a DT cord-002542-f7l4ty2j 407 25 shorter short JJR cord-002542-f7l4ty2j 407 26 defective defective JJ cord-002542-f7l4ty2j 407 27 RNA RNA NNP cord-002542-f7l4ty2j 407 28 would would MD cord-002542-f7l4ty2j 407 29 be be VB cord-002542-f7l4ty2j 407 30 replicated replicate VBN cord-002542-f7l4ty2j 407 31 more more RBR cord-002542-f7l4ty2j 407 32 quickly quickly RB cord-002542-f7l4ty2j 407 33 and and CC cord-002542-f7l4ty2j 407 34 thus thus RB cord-002542-f7l4ty2j 407 35 more more RBR cord-002542-f7l4ty2j 407 36 competitively competitively RB cord-002542-f7l4ty2j 407 37 [ [ -LRB- cord-002542-f7l4ty2j 407 38 10 10 CD cord-002542-f7l4ty2j 407 39 ] ] -RRB- cord-002542-f7l4ty2j 407 40 . . . cord-002542-f7l4ty2j 408 1 In in IN cord-002542-f7l4ty2j 408 2 our -PRON- PRP$ cord-002542-f7l4ty2j 408 3 analysis analysis NN cord-002542-f7l4ty2j 408 4 , , , cord-002542-f7l4ty2j 408 5 while while IN cord-002542-f7l4ty2j 408 6 the~250 the~250 NNP cord-002542-f7l4ty2j 408 7 - - HYPH cord-002542-f7l4ty2j 408 8 550 550 CD cord-002542-f7l4ty2j 408 9 deletion deletion NN cord-002542-f7l4ty2j 408 10 in in IN cord-002542-f7l4ty2j 408 11 RNA2 RNA2 NNP cord-002542-f7l4ty2j 408 12 ( ( -LRB- cord-002542-f7l4ty2j 408 13 for for IN cord-002542-f7l4ty2j 408 14 example example NN cord-002542-f7l4ty2j 408 15 ) ) -RRB- cord-002542-f7l4ty2j 408 16 is be VBZ cord-002542-f7l4ty2j 408 17 very very RB cord-002542-f7l4ty2j 408 18 common common JJ cord-002542-f7l4ty2j 408 19 we -PRON- PRP cord-002542-f7l4ty2j 408 20 do do VBP cord-002542-f7l4ty2j 408 21 not not RB cord-002542-f7l4ty2j 408 22 observe observe VB cord-002542-f7l4ty2j 408 23 the the DT cord-002542-f7l4ty2j 408 24 accumulation accumulation NN cord-002542-f7l4ty2j 408 25 of of IN cord-002542-f7l4ty2j 408 26 deletion deletion NN cord-002542-f7l4ty2j 408 27 events event NNS cord-002542-f7l4ty2j 408 28 that that WDT cord-002542-f7l4ty2j 408 29 are be VBP cord-002542-f7l4ty2j 408 30 smaller small JJR cord-002542-f7l4ty2j 408 31 than than IN cord-002542-f7l4ty2j 408 32 this this DT cord-002542-f7l4ty2j 408 33 ( ( -LRB- cord-002542-f7l4ty2j 408 34 e.g. e.g. RB cord-002542-f7l4ty2j 408 35 300 300 CD cord-002542-f7l4ty2j 408 36 - - SYM cord-002542-f7l4ty2j 408 37 450 450 CD cord-002542-f7l4ty2j 408 38 ) ) -RRB- cord-002542-f7l4ty2j 408 39 . . . cord-002542-f7l4ty2j 409 1 This this DT cord-002542-f7l4ty2j 409 2 is be VBZ cord-002542-f7l4ty2j 409 3 despite despite IN cord-002542-f7l4ty2j 409 4 the the DT cord-002542-f7l4ty2j 409 5 fact fact NN cord-002542-f7l4ty2j 409 6 that that IN cord-002542-f7l4ty2j 409 7 we -PRON- PRP cord-002542-f7l4ty2j 409 8 can can MD cord-002542-f7l4ty2j 409 9 detect detect VB cord-002542-f7l4ty2j 409 10 and and CC cord-002542-f7l4ty2j 409 11 observe observe VB cord-002542-f7l4ty2j 409 12 such such JJ cord-002542-f7l4ty2j 409 13 species specie NNS cord-002542-f7l4ty2j 409 14 in in IN cord-002542-f7l4ty2j 409 15 low low JJ cord-002542-f7l4ty2j 409 16 frequencies frequency NNS cord-002542-f7l4ty2j 409 17 both both DT cord-002542-f7l4ty2j 409 18 in in IN cord-002542-f7l4ty2j 409 19 early early JJ cord-002542-f7l4ty2j 409 20 and and CC cord-002542-f7l4ty2j 409 21 late late JJ cord-002542-f7l4ty2j 409 22 passages passage NNS cord-002542-f7l4ty2j 409 23 , , , cord-002542-f7l4ty2j 409 24 suggesting suggest VBG cord-002542-f7l4ty2j 409 25 that that IN cord-002542-f7l4ty2j 409 26 they -PRON- PRP cord-002542-f7l4ty2j 409 27 are be VBP cord-002542-f7l4ty2j 409 28 indeed indeed RB cord-002542-f7l4ty2j 409 29 generated generate VBN cord-002542-f7l4ty2j 409 30 but but CC cord-002542-f7l4ty2j 409 31 are be VBP cord-002542-f7l4ty2j 409 32 not not RB cord-002542-f7l4ty2j 409 33 selectively selectively RB cord-002542-f7l4ty2j 409 34 amplified amplify VBN cord-002542-f7l4ty2j 409 35 . . . cord-002542-f7l4ty2j 410 1 This this DT cord-002542-f7l4ty2j 410 2 may may MD cord-002542-f7l4ty2j 410 3 in in IN cord-002542-f7l4ty2j 410 4 part part NN cord-002542-f7l4ty2j 410 5 be be VB cord-002542-f7l4ty2j 410 6 due due JJ cord-002542-f7l4ty2j 410 7 to to IN cord-002542-f7l4ty2j 410 8 selecting select VBG cord-002542-f7l4ty2j 410 9 for for IN cord-002542-f7l4ty2j 410 10 DI DI NNP cord-002542-f7l4ty2j 410 11 - - HYPH cord-002542-f7l4ty2j 410 12 RNA RNA NNP cord-002542-f7l4ty2j 410 13 genomes genome NNS cord-002542-f7l4ty2j 410 14 that that WDT cord-002542-f7l4ty2j 410 15 are be VBP cord-002542-f7l4ty2j 410 16 as as RB cord-002542-f7l4ty2j 410 17 small small JJ cord-002542-f7l4ty2j 410 18 as as IN cord-002542-f7l4ty2j 410 19 possible possible JJ cord-002542-f7l4ty2j 410 20 , , , cord-002542-f7l4ty2j 410 21 while while IN cord-002542-f7l4ty2j 410 22 retaining retain VBG cord-002542-f7l4ty2j 410 23 the the DT cord-002542-f7l4ty2j 410 24 minimal minimal JJ cord-002542-f7l4ty2j 410 25 amount amount NN cord-002542-f7l4ty2j 410 26 of of IN cord-002542-f7l4ty2j 410 27 genetic genetic JJ cord-002542-f7l4ty2j 410 28 material material NN cord-002542-f7l4ty2j 410 29 to to TO cord-002542-f7l4ty2j 410 30 form form VB cord-002542-f7l4ty2j 410 31 functional functional JJ cord-002542-f7l4ty2j 410 32 genetic genetic JJ cord-002542-f7l4ty2j 410 33 elements element NNS cord-002542-f7l4ty2j 410 34 . . . cord-002542-f7l4ty2j 411 1 However however RB cord-002542-f7l4ty2j 411 2 , , , cord-002542-f7l4ty2j 411 3 it -PRON- PRP cord-002542-f7l4ty2j 411 4 may may MD cord-002542-f7l4ty2j 411 5 also also RB cord-002542-f7l4ty2j 411 6 be be VB cord-002542-f7l4ty2j 411 7 the the DT cord-002542-f7l4ty2j 411 8 result result NN cord-002542-f7l4ty2j 411 9 of of IN cord-002542-f7l4ty2j 411 10 a a DT cord-002542-f7l4ty2j 411 11 negative negative JJ cord-002542-f7l4ty2j 411 12 selection selection NN cord-002542-f7l4ty2j 411 13 pressure pressure NN cord-002542-f7l4ty2j 411 14 or or CC cord-002542-f7l4ty2j 411 15 restrictive restrictive JJ cord-002542-f7l4ty2j 411 16 barrier barrier NN cord-002542-f7l4ty2j 411 17 that that WDT cord-002542-f7l4ty2j 411 18 is be VBZ cord-002542-f7l4ty2j 411 19 released release VBN cord-002542-f7l4ty2j 411 20 only only RB cord-002542-f7l4ty2j 411 21 after after IN cord-002542-f7l4ty2j 411 22 excising excise VBG cord-002542-f7l4ty2j 411 23 specific specific JJ cord-002542-f7l4ty2j 411 24 portions portion NNS cord-002542-f7l4ty2j 411 25 of of IN cord-002542-f7l4ty2j 411 26 the the DT cord-002542-f7l4ty2j 411 27 viral viral JJ cord-002542-f7l4ty2j 411 28 genome genome NN cord-002542-f7l4ty2j 411 29 . . . cord-002542-f7l4ty2j 412 1 An an DT cord-002542-f7l4ty2j 412 2 example example NN cord-002542-f7l4ty2j 412 3 of of IN cord-002542-f7l4ty2j 412 4 this this DT cord-002542-f7l4ty2j 412 5 scenario scenario NN cord-002542-f7l4ty2j 412 6 has have VBZ cord-002542-f7l4ty2j 412 7 been be VBN cord-002542-f7l4ty2j 412 8 demonstrated demonstrate VBN cord-002542-f7l4ty2j 412 9 for for IN cord-002542-f7l4ty2j 412 10 tomato tomato NN cord-002542-f7l4ty2j 412 11 bushy bushy JJ cord-002542-f7l4ty2j 412 12 stunt stunt NN cord-002542-f7l4ty2j 412 13 virus virus NN cord-002542-f7l4ty2j 412 14 ( ( -LRB- cord-002542-f7l4ty2j 412 15 TBSV TBSV NNP cord-002542-f7l4ty2j 412 16 ) ) -RRB- cord-002542-f7l4ty2j 412 17 associated associate VBD cord-002542-f7l4ty2j 412 18 DI DI NNP cord-002542-f7l4ty2j 412 19 - - HYPH cord-002542-f7l4ty2j 412 20 RNAs rna NNS cord-002542-f7l4ty2j 412 21 whereby whereby VBZ cord-002542-f7l4ty2j 412 22 deletion deletion NN cord-002542-f7l4ty2j 412 23 of of IN cord-002542-f7l4ty2j 412 24 a a DT cord-002542-f7l4ty2j 412 25 translation translation NN cord-002542-f7l4ty2j 412 26 enhancer enhancer NN cord-002542-f7l4ty2j 412 27 functional functional JJ cord-002542-f7l4ty2j 412 28 element element NN cord-002542-f7l4ty2j 412 29 removes remove VBZ cord-002542-f7l4ty2j 412 30 the the DT cord-002542-f7l4ty2j 412 31 competition competition NN cord-002542-f7l4ty2j 412 32 between between IN cord-002542-f7l4ty2j 412 33 translation translation NN cord-002542-f7l4ty2j 412 34 and and CC cord-002542-f7l4ty2j 412 35 replication replication NN cord-002542-f7l4ty2j 412 36 , , , cord-002542-f7l4ty2j 412 37 thus thus RB cord-002542-f7l4ty2j 412 38 favoring favor VBG cord-002542-f7l4ty2j 412 39 replication replication NN cord-002542-f7l4ty2j 412 40 of of IN cord-002542-f7l4ty2j 412 41 the the DT cord-002542-f7l4ty2j 412 42 smaller small JJR cord-002542-f7l4ty2j 412 43 DI DI NNP cord-002542-f7l4ty2j 412 44 - - HYPH cord-002542-f7l4ty2j 412 45 RNA RNA NNP cord-002542-f7l4ty2j 412 46 [ [ -LRB- cord-002542-f7l4ty2j 412 47 68 68 CD cord-002542-f7l4ty2j 412 48 ] ] -RRB- cord-002542-f7l4ty2j 412 49 . . . cord-002542-f7l4ty2j 413 1 Therefore therefore RB cord-002542-f7l4ty2j 413 2 , , , cord-002542-f7l4ty2j 413 3 the the DT cord-002542-f7l4ty2j 413 4 final final JJ cord-002542-f7l4ty2j 413 5 structure structure NN cord-002542-f7l4ty2j 413 6 of of IN cord-002542-f7l4ty2j 413 7 DI DI NNP cord-002542-f7l4ty2j 413 8 - - HYPH cord-002542-f7l4ty2j 413 9 RNAs rna NNS cord-002542-f7l4ty2j 413 10 may may MD cord-002542-f7l4ty2j 413 11 depend depend VB cord-002542-f7l4ty2j 413 12 both both DT cord-002542-f7l4ty2j 413 13 on on IN cord-002542-f7l4ty2j 413 14 the the DT cord-002542-f7l4ty2j 413 15 retention retention NN cord-002542-f7l4ty2j 413 16 of of IN cord-002542-f7l4ty2j 413 17 essential essential JJ cord-002542-f7l4ty2j 413 18 functional functional JJ cord-002542-f7l4ty2j 413 19 RNA RNA NNP cord-002542-f7l4ty2j 413 20 elements element NNS cord-002542-f7l4ty2j 413 21 , , , cord-002542-f7l4ty2j 413 22 as as RB cord-002542-f7l4ty2j 413 23 well well RB cord-002542-f7l4ty2j 413 24 as as IN cord-002542-f7l4ty2j 413 25 the the DT cord-002542-f7l4ty2j 413 26 removal removal NN cord-002542-f7l4ty2j 413 27 of of IN cord-002542-f7l4ty2j 413 28 restrictive restrictive JJ cord-002542-f7l4ty2j 413 29 barriers barrier NNS cord-002542-f7l4ty2j 413 30 that that WDT cord-002542-f7l4ty2j 413 31 attenuate attenuate VBP cord-002542-f7l4ty2j 413 32 RNA RNA NNP cord-002542-f7l4ty2j 413 33 replication replication NN cord-002542-f7l4ty2j 413 34 . . . cord-002542-f7l4ty2j 414 1 One one CD cord-002542-f7l4ty2j 414 2 model model NN cord-002542-f7l4ty2j 414 3 for for IN cord-002542-f7l4ty2j 414 4 the the DT cord-002542-f7l4ty2j 414 5 evolution evolution NN cord-002542-f7l4ty2j 414 6 of of IN cord-002542-f7l4ty2j 414 7 DI DI NNP cord-002542-f7l4ty2j 414 8 - - HYPH cord-002542-f7l4ty2j 414 9 RNAs RNAs NNPS cord-002542-f7l4ty2j 414 10 is be VBZ cord-002542-f7l4ty2j 414 11 through through IN cord-002542-f7l4ty2j 414 12 the the DT cord-002542-f7l4ty2j 414 13 step step NN cord-002542-f7l4ty2j 414 14 - - HYPH cord-002542-f7l4ty2j 414 15 wise wise JJ cord-002542-f7l4ty2j 414 16 accumulation accumulation NN cord-002542-f7l4ty2j 414 17 of of IN cord-002542-f7l4ty2j 414 18 deletion deletion NN cord-002542-f7l4ty2j 414 19 events event NNS cord-002542-f7l4ty2j 414 20 through through IN cord-002542-f7l4ty2j 414 21 a a DT cord-002542-f7l4ty2j 414 22 series series NN cord-002542-f7l4ty2j 414 23 of of IN cord-002542-f7l4ty2j 414 24 individual individual JJ cord-002542-f7l4ty2j 414 25 recombination recombination NN cord-002542-f7l4ty2j 414 26 events event NNS cord-002542-f7l4ty2j 414 27 [ [ -LRB- cord-002542-f7l4ty2j 414 28 68 68 CD cord-002542-f7l4ty2j 414 29 ] ] -RRB- cord-002542-f7l4ty2j 414 30 . . . cord-002542-f7l4ty2j 415 1 The the DT cord-002542-f7l4ty2j 415 2 MinION minion NN cord-002542-f7l4ty2j 415 3 data datum NNS cord-002542-f7l4ty2j 415 4 reveals reveal VBZ cord-002542-f7l4ty2j 415 5 that that IN cord-002542-f7l4ty2j 415 6 the the DT cord-002542-f7l4ty2j 415 7 defective defective JJ cord-002542-f7l4ty2j 415 8 RNAs rna NNS cord-002542-f7l4ty2j 415 9 that that WDT cord-002542-f7l4ty2j 415 10 accumulate accumulate VBP cord-002542-f7l4ty2j 415 11 ( ( -LRB- cord-002542-f7l4ty2j 415 12 rapidly rapidly RB cord-002542-f7l4ty2j 415 13 over over IN cord-002542-f7l4ty2j 415 14 the the DT cord-002542-f7l4ty2j 415 15 course course NN cord-002542-f7l4ty2j 415 16 2 2 CD cord-002542-f7l4ty2j 415 17 - - SYM cord-002542-f7l4ty2j 415 18 3 3 CD cord-002542-f7l4ty2j 415 19 passages passage NNS cord-002542-f7l4ty2j 415 20 ) ) -RRB- cord-002542-f7l4ty2j 415 21 contain contain VBP cord-002542-f7l4ty2j 415 22 multiple multiple JJ cord-002542-f7l4ty2j 415 23 deletion deletion NN cord-002542-f7l4ty2j 415 24 events event NNS cord-002542-f7l4ty2j 415 25 . . . cord-002542-f7l4ty2j 416 1 However however RB cord-002542-f7l4ty2j 416 2 , , , cord-002542-f7l4ty2j 416 3 we -PRON- PRP cord-002542-f7l4ty2j 416 4 do do VBP cord-002542-f7l4ty2j 416 5 not not RB cord-002542-f7l4ty2j 416 6 see see VB cord-002542-f7l4ty2j 416 7 the the DT cord-002542-f7l4ty2j 416 8 rapid rapid JJ cord-002542-f7l4ty2j 416 9 accumulation accumulation NN cord-002542-f7l4ty2j 416 10 of of IN cord-002542-f7l4ty2j 416 11 the the DT cord-002542-f7l4ty2j 416 12 intermediate intermediate JJ cord-002542-f7l4ty2j 416 13 DI DI NNP cord-002542-f7l4ty2j 416 14 - - HYPH cord-002542-f7l4ty2j 416 15 RNAs rna NNS cord-002542-f7l4ty2j 416 16 , , , cord-002542-f7l4ty2j 416 17 despite despite IN cord-002542-f7l4ty2j 416 18 evidence evidence NN cord-002542-f7l4ty2j 416 19 for for IN cord-002542-f7l4ty2j 416 20 their -PRON- PRP$ cord-002542-f7l4ty2j 416 21 presence presence NN cord-002542-f7l4ty2j 416 22 early early RB cord-002542-f7l4ty2j 416 23 in in IN cord-002542-f7l4ty2j 416 24 viral viral JJ cord-002542-f7l4ty2j 416 25 passaging passaging NN cord-002542-f7l4ty2j 416 26 . . . cord-002542-f7l4ty2j 417 1 This this DT cord-002542-f7l4ty2j 417 2 suggests suggest VBZ cord-002542-f7l4ty2j 417 3 that that IN cord-002542-f7l4ty2j 417 4 the the DT cord-002542-f7l4ty2j 417 5 mature mature JJ cord-002542-f7l4ty2j 417 6 DI DI NNP cord-002542-f7l4ty2j 417 7 - - HYPH cord-002542-f7l4ty2j 417 8 R R NNP cord-002542-f7l4ty2j 417 9 - - HYPH cord-002542-f7l4ty2j 417 10 NAs NAs NNPS cord-002542-f7l4ty2j 417 11 have have VBP cord-002542-f7l4ty2j 417 12 a a DT cord-002542-f7l4ty2j 417 13 competitive competitive JJ cord-002542-f7l4ty2j 417 14 advantage advantage NN cord-002542-f7l4ty2j 417 15 over over IN cord-002542-f7l4ty2j 417 16 their -PRON- PRP$ cord-002542-f7l4ty2j 417 17 presumed presume VBN cord-002542-f7l4ty2j 417 18 intermediate intermediate JJ cord-002542-f7l4ty2j 417 19 precursors precursor NNS cord-002542-f7l4ty2j 417 20 . . . cord-002542-f7l4ty2j 418 1 If if IN cord-002542-f7l4ty2j 418 2 this this DT cord-002542-f7l4ty2j 418 3 is be VBZ cord-002542-f7l4ty2j 418 4 the the DT cord-002542-f7l4ty2j 418 5 case case NN cord-002542-f7l4ty2j 418 6 , , , cord-002542-f7l4ty2j 418 7 the the DT cord-002542-f7l4ty2j 418 8 multiple multiple JJ cord-002542-f7l4ty2j 418 9 deletions deletion NNS cord-002542-f7l4ty2j 418 10 may may MD cord-002542-f7l4ty2j 418 11 function function VB cord-002542-f7l4ty2j 418 12 epistatically epistatically RB cord-002542-f7l4ty2j 418 13 either either CC cord-002542-f7l4ty2j 418 14 through through IN cord-002542-f7l4ty2j 418 15 an an DT cord-002542-f7l4ty2j 418 16 undefined undefined JJ cord-002542-f7l4ty2j 418 17 cooperative cooperative JJ cord-002542-f7l4ty2j 418 18 / / SYM cord-002542-f7l4ty2j 418 19 additive additive NN cord-002542-f7l4ty2j 418 20 mechanism mechanism NN cord-002542-f7l4ty2j 418 21 or or CC cord-002542-f7l4ty2j 418 22 through through IN cord-002542-f7l4ty2j 418 23 the the DT cord-002542-f7l4ty2j 418 24 release release NN cord-002542-f7l4ty2j 418 25 of of IN cord-002542-f7l4ty2j 418 26 multiple multiple JJ cord-002542-f7l4ty2j 418 27 restriction restriction NN cord-002542-f7l4ty2j 418 28 barriers barrier NNS cord-002542-f7l4ty2j 418 29 , , , cord-002542-f7l4ty2j 418 30 as as IN cord-002542-f7l4ty2j 418 31 proposed propose VBN cord-002542-f7l4ty2j 418 32 above above RB cord-002542-f7l4ty2j 418 33 . . . cord-002542-f7l4ty2j 419 1 If if IN cord-002542-f7l4ty2j 419 2 multiple multiple JJ cord-002542-f7l4ty2j 419 3 restriction restriction NN cord-002542-f7l4ty2j 419 4 barriers barrier NNS cord-002542-f7l4ty2j 419 5 are be VBP cord-002542-f7l4ty2j 419 6 required require VBN cord-002542-f7l4ty2j 419 7 to to TO cord-002542-f7l4ty2j 419 8 be be VB cord-002542-f7l4ty2j 419 9 excised excise VBN cord-002542-f7l4ty2j 419 10 for for IN cord-002542-f7l4ty2j 419 11 the the DT cord-002542-f7l4ty2j 419 12 formation formation NN cord-002542-f7l4ty2j 419 13 of of IN cord-002542-f7l4ty2j 419 14 DI DI NNP cord-002542-f7l4ty2j 419 15 - - HYPH cord-002542-f7l4ty2j 419 16 RNAs rna NNS cord-002542-f7l4ty2j 419 17 , , , cord-002542-f7l4ty2j 419 18 small small JJ cord-002542-f7l4ty2j 419 19 or or CC cord-002542-f7l4ty2j 419 20 multipartite multipartite NNP cord-002542-f7l4ty2j 419 21 RNA RNA NNP cord-002542-f7l4ty2j 419 22 viruses virus NNS cord-002542-f7l4ty2j 419 23 , , , cord-002542-f7l4ty2j 419 24 such such JJ cord-002542-f7l4ty2j 419 25 as as IN cord-002542-f7l4ty2j 419 26 FHV FHV NNP cord-002542-f7l4ty2j 419 27 or or CC cord-002542-f7l4ty2j 419 28 influenza influenza NN cord-002542-f7l4ty2j 419 29 [ [ -LRB- cord-002542-f7l4ty2j 419 30 17 17 CD cord-002542-f7l4ty2j 419 31 ] ] -RRB- cord-002542-f7l4ty2j 419 32 , , , cord-002542-f7l4ty2j 419 33 may may MD cord-002542-f7l4ty2j 419 34 therefore therefore RB cord-002542-f7l4ty2j 419 35 generate generate VB cord-002542-f7l4ty2j 419 36 DI DI NNP cord-002542-f7l4ty2j 419 37 - - HYPH cord-002542-f7l4ty2j 419 38 RNAs rna NNS cord-002542-f7l4ty2j 419 39 more more RBR cord-002542-f7l4ty2j 419 40 readily readily RB cord-002542-f7l4ty2j 419 41 by by IN cord-002542-f7l4ty2j 419 42 requiring require VBG cord-002542-f7l4ty2j 419 43 fewer few JJR cord-002542-f7l4ty2j 419 44 intermediate intermediate JJ cord-002542-f7l4ty2j 419 45 steps step NNS cord-002542-f7l4ty2j 419 46 than than IN cord-002542-f7l4ty2j 419 47 long long RB cord-002542-f7l4ty2j 419 48 , , , cord-002542-f7l4ty2j 419 49 monopartite monopartite NNP cord-002542-f7l4ty2j 419 50 RNA RNA NNP cord-002542-f7l4ty2j 419 51 viruses virus NNS cord-002542-f7l4ty2j 419 52 . . . cord-002542-f7l4ty2j 420 1 Moreover moreover RB cord-002542-f7l4ty2j 420 2 , , , cord-002542-f7l4ty2j 420 3 if if IN cord-002542-f7l4ty2j 420 4 intermediate intermediate JJ cord-002542-f7l4ty2j 420 5 defective defective JJ cord-002542-f7l4ty2j 420 6 RNAs rna NNS cord-002542-f7l4ty2j 420 7 fail fail VBP cord-002542-f7l4ty2j 420 8 to to TO cord-002542-f7l4ty2j 420 9 accumulate accumulate VB cord-002542-f7l4ty2j 420 10 , , , cord-002542-f7l4ty2j 420 11 this this DT cord-002542-f7l4ty2j 420 12 reduces reduce VBZ cord-002542-f7l4ty2j 420 13 the the DT cord-002542-f7l4ty2j 420 14 likelihood likelihood NN cord-002542-f7l4ty2j 420 15 that that IN cord-002542-f7l4ty2j 420 16 mature mature JJ cord-002542-f7l4ty2j 420 17 DI DI NNP cord-002542-f7l4ty2j 420 18 - - HYPH cord-002542-f7l4ty2j 420 19 RNAs rna NNS cord-002542-f7l4ty2j 420 20 can can MD cord-002542-f7l4ty2j 420 21 subsequently subsequently RB cord-002542-f7l4ty2j 420 22 be be VB cord-002542-f7l4ty2j 420 23 generated generate VBN cord-002542-f7l4ty2j 420 24 and and CC cord-002542-f7l4ty2j 420 25 may may MD cord-002542-f7l4ty2j 420 26 place place VB cord-002542-f7l4ty2j 420 27 substantial substantial JJ cord-002542-f7l4ty2j 420 28 limitations limitation NNS cord-002542-f7l4ty2j 420 29 on on IN cord-002542-f7l4ty2j 420 30 the the DT cord-002542-f7l4ty2j 420 31 ability ability NN cord-002542-f7l4ty2j 420 32 of of IN cord-002542-f7l4ty2j 420 33 some some DT cord-002542-f7l4ty2j 420 34 viruses virus NNS cord-002542-f7l4ty2j 420 35 to to TO cord-002542-f7l4ty2j 420 36 generate generate VB cord-002542-f7l4ty2j 420 37 DI DI NNP cord-002542-f7l4ty2j 420 38 - - HYPH cord-002542-f7l4ty2j 420 39 RNAs rna NNS cord-002542-f7l4ty2j 420 40 altogether altogether RB cord-002542-f7l4ty2j 420 41 . . . cord-002542-f7l4ty2j 421 1 An an DT cord-002542-f7l4ty2j 421 2 alternative alternative JJ cord-002542-f7l4ty2j 421 3 reason reason NN cord-002542-f7l4ty2j 421 4 for for IN cord-002542-f7l4ty2j 421 5 the the DT cord-002542-f7l4ty2j 421 6 rarity rarity NN cord-002542-f7l4ty2j 421 7 of of IN cord-002542-f7l4ty2j 421 8 precursor precursor NN cord-002542-f7l4ty2j 421 9 / / SYM cord-002542-f7l4ty2j 421 10 intermediate intermediate JJ cord-002542-f7l4ty2j 421 11 defective defective JJ cord-002542-f7l4ty2j 421 12 RNAs rna NNS cord-002542-f7l4ty2j 421 13 is be VBZ cord-002542-f7l4ty2j 421 14 that that IN cord-002542-f7l4ty2j 421 15 the the DT cord-002542-f7l4ty2j 421 16 mature mature JJ cord-002542-f7l4ty2j 421 17 DI DI NNP cord-002542-f7l4ty2j 421 18 - - HYPH cord-002542-f7l4ty2j 421 19 RNAs rna NNS cord-002542-f7l4ty2j 421 20 are be VBP cord-002542-f7l4ty2j 421 21 generated generate VBN cord-002542-f7l4ty2j 421 22 in in IN cord-002542-f7l4ty2j 421 23 one one CD cord-002542-f7l4ty2j 421 24 single single JJ cord-002542-f7l4ty2j 421 25 event event NN cord-002542-f7l4ty2j 421 26 . . . cord-002542-f7l4ty2j 422 1 We -PRON- PRP cord-002542-f7l4ty2j 422 2 are be VBP cord-002542-f7l4ty2j 422 3 yet yet RB cord-002542-f7l4ty2j 422 4 to to TO cord-002542-f7l4ty2j 422 5 determine determine VB cord-002542-f7l4ty2j 422 6 the the DT cord-002542-f7l4ty2j 422 7 molecular molecular JJ cord-002542-f7l4ty2j 422 8 mechanism mechanism NN cord-002542-f7l4ty2j 422 9 of of IN cord-002542-f7l4ty2j 422 10 recombination recombination NN cord-002542-f7l4ty2j 422 11 that that WDT cord-002542-f7l4ty2j 422 12 leads lead VBZ cord-002542-f7l4ty2j 422 13 to to IN cord-002542-f7l4ty2j 422 14 DI DI NNP cord-002542-f7l4ty2j 422 15 - - HYPH cord-002542-f7l4ty2j 422 16 RNA RNA NNP cord-002542-f7l4ty2j 422 17 formation formation NN cord-002542-f7l4ty2j 422 18 . . . cord-002542-f7l4ty2j 423 1 Both both DT cord-002542-f7l4ty2j 423 2 template template NN cord-002542-f7l4ty2j 423 3 - - HYPH cord-002542-f7l4ty2j 423 4 switching switch VBG cord-002542-f7l4ty2j 423 5 , , , cord-002542-f7l4ty2j 423 6 secondary secondary JJ cord-002542-f7l4ty2j 423 7 - - HYPH cord-002542-f7l4ty2j 423 8 structure structure NN cord-002542-f7l4ty2j 423 9 jumping jumping NN cord-002542-f7l4ty2j 423 10 , , , cord-002542-f7l4ty2j 423 11 and and CC cord-002542-f7l4ty2j 423 12 non non JJ cord-002542-f7l4ty2j 423 13 - - JJ cord-002542-f7l4ty2j 423 14 replicative replicative JJ cord-002542-f7l4ty2j 423 15 mechanisms mechanism NNS cord-002542-f7l4ty2j 423 16 have have VBP cord-002542-f7l4ty2j 423 17 been be VBN cord-002542-f7l4ty2j 423 18 proposed propose VBN cord-002542-f7l4ty2j 423 19 , , , cord-002542-f7l4ty2j 423 20 and and CC cord-002542-f7l4ty2j 423 21 indeed indeed RB cord-002542-f7l4ty2j 423 22 these these DT cord-002542-f7l4ty2j 423 23 mechanisms mechanism NNS cord-002542-f7l4ty2j 423 24 need nee MD cord-002542-f7l4ty2j 423 25 not not RB cord-002542-f7l4ty2j 423 26 be be VB cord-002542-f7l4ty2j 423 27 mutually mutually RB cord-002542-f7l4ty2j 423 28 exclusive exclusive JJ cord-002542-f7l4ty2j 423 29 . . . cord-002542-f7l4ty2j 424 1 Our -PRON- PRP$ cord-002542-f7l4ty2j 424 2 observation observation NN cord-002542-f7l4ty2j 424 3 of of IN cord-002542-f7l4ty2j 424 4 nucleotide nucleotide JJ cord-002542-f7l4ty2j 424 5 preferences preference NNS cord-002542-f7l4ty2j 424 6 at at IN cord-002542-f7l4ty2j 424 7 recombination recombination NN cord-002542-f7l4ty2j 424 8 junctions junction NNS cord-002542-f7l4ty2j 424 9 ( ( -LRB- cord-002542-f7l4ty2j 424 10 Fig Fig NNP cord-002542-f7l4ty2j 424 11 2C 2c NN cord-002542-f7l4ty2j 424 12 ) ) -RRB- cord-002542-f7l4ty2j 424 13 may may MD cord-002542-f7l4ty2j 424 14 arise arise VB cord-002542-f7l4ty2j 424 15 through through IN cord-002542-f7l4ty2j 424 16 any any DT cord-002542-f7l4ty2j 424 17 of of IN cord-002542-f7l4ty2j 424 18 these these DT cord-002542-f7l4ty2j 424 19 potential potential JJ cord-002542-f7l4ty2j 424 20 mechanisms mechanism NNS cord-002542-f7l4ty2j 424 21 . . . cord-002542-f7l4ty2j 425 1 Alternatively alternatively RB cord-002542-f7l4ty2j 425 2 , , , cord-002542-f7l4ty2j 425 3 it -PRON- PRP cord-002542-f7l4ty2j 425 4 is be VBZ cord-002542-f7l4ty2j 425 5 possible possible JJ cord-002542-f7l4ty2j 425 6 that that IN cord-002542-f7l4ty2j 425 7 multiple multiple JJ cord-002542-f7l4ty2j 425 8 reassembly reassembly NN cord-002542-f7l4ty2j 425 9 / / SYM cord-002542-f7l4ty2j 425 10 deletion deletion NN cord-002542-f7l4ty2j 425 11 events event NNS cord-002542-f7l4ty2j 425 12 occur occur VBP cord-002542-f7l4ty2j 425 13 in in IN cord-002542-f7l4ty2j 425 14 a a DT cord-002542-f7l4ty2j 425 15 single single JJ cord-002542-f7l4ty2j 425 16 step step NN cord-002542-f7l4ty2j 425 17 , , , cord-002542-f7l4ty2j 425 18 in in IN cord-002542-f7l4ty2j 425 19 a a DT cord-002542-f7l4ty2j 425 20 manner manner NN cord-002542-f7l4ty2j 425 21 reminiscent reminiscent JJ cord-002542-f7l4ty2j 425 22 of of IN cord-002542-f7l4ty2j 425 23 chromosome chromosome NN cord-002542-f7l4ty2j 425 24 shattering shattering NN cord-002542-f7l4ty2j 425 25 ( ( -LRB- cord-002542-f7l4ty2j 425 26 chromothripsis chromothripsis NNP cord-002542-f7l4ty2j 425 27 ) ) -RRB- cord-002542-f7l4ty2j 425 28 [ [ -LRB- cord-002542-f7l4ty2j 425 29 69 69 CD cord-002542-f7l4ty2j 425 30 ] ] -RRB- cord-002542-f7l4ty2j 425 31 ; ; : cord-002542-f7l4ty2j 425 32 or or CC cord-002542-f7l4ty2j 425 33 ' ' `` cord-002542-f7l4ty2j 425 34 virothripsis virothripsis NN cord-002542-f7l4ty2j 425 35 ' ' '' cord-002542-f7l4ty2j 425 36 . . . cord-002542-f7l4ty2j 426 1 Within within IN cord-002542-f7l4ty2j 426 2 the the DT cord-002542-f7l4ty2j 426 3 confined confined JJ cord-002542-f7l4ty2j 426 4 invaginations invagination NNS cord-002542-f7l4ty2j 426 5 of of IN cord-002542-f7l4ty2j 426 6 the the DT cord-002542-f7l4ty2j 426 7 mitochondrial mitochondrial JJ cord-002542-f7l4ty2j 426 8 membranes membrane NNS cord-002542-f7l4ty2j 426 9 that that WDT cord-002542-f7l4ty2j 426 10 form form VBP cord-002542-f7l4ty2j 426 11 the the DT cord-002542-f7l4ty2j 426 12 replication replication NN cord-002542-f7l4ty2j 426 13 factories factory NNS cord-002542-f7l4ty2j 426 14 of of IN cord-002542-f7l4ty2j 426 15 RNA RNA NNP cord-002542-f7l4ty2j 426 16 viruses virus NNS cord-002542-f7l4ty2j 426 17 such such JJ cord-002542-f7l4ty2j 426 18 as as IN cord-002542-f7l4ty2j 426 19 FHV FHV NNP cord-002542-f7l4ty2j 426 20 [ [ -LRB- cord-002542-f7l4ty2j 426 21 70 70 CD cord-002542-f7l4ty2j 426 22 ] ] -RRB- cord-002542-f7l4ty2j 426 23 , , , cord-002542-f7l4ty2j 426 24 the the DT cord-002542-f7l4ty2j 426 25 fragmentation fragmentation NN cord-002542-f7l4ty2j 426 26 the the DT cord-002542-f7l4ty2j 426 27 RNA RNA NNP cord-002542-f7l4ty2j 426 28 virus virus NN cord-002542-f7l4ty2j 426 29 genome genome NN cord-002542-f7l4ty2j 426 30 followed follow VBN cord-002542-f7l4ty2j 426 31 by by IN cord-002542-f7l4ty2j 426 32 incorrect incorrect JJ cord-002542-f7l4ty2j 426 33 re re NN cord-002542-f7l4ty2j 426 34 - - NN cord-002542-f7l4ty2j 426 35 stitching stitching NN cord-002542-f7l4ty2j 426 36 of of IN cord-002542-f7l4ty2j 426 37 these these DT cord-002542-f7l4ty2j 426 38 genome genome NN cord-002542-f7l4ty2j 426 39 pieces piece NNS cord-002542-f7l4ty2j 426 40 , , , cord-002542-f7l4ty2j 426 41 either either CC cord-002542-f7l4ty2j 426 42 through through IN cord-002542-f7l4ty2j 426 43 forced force VBN cord-002542-f7l4ty2j 426 44 - - HYPH cord-002542-f7l4ty2j 426 45 copy copy NN cord-002542-f7l4ty2j 426 46 choice choice NN cord-002542-f7l4ty2j 426 47 template template NN cord-002542-f7l4ty2j 426 48 switching switch VBG cord-002542-f7l4ty2j 426 49 or or CC cord-002542-f7l4ty2j 426 50 a a DT cord-002542-f7l4ty2j 426 51 non non JJ cord-002542-f7l4ty2j 426 52 - - JJ cord-002542-f7l4ty2j 426 53 replicative replicative JJ cord-002542-f7l4ty2j 426 54 mechanism mechanism NN cord-002542-f7l4ty2j 426 55 , , , cord-002542-f7l4ty2j 426 56 could could MD cord-002542-f7l4ty2j 426 57 create create VB cord-002542-f7l4ty2j 426 58 the the DT cord-002542-f7l4ty2j 426 59 DI DI NNP cord-002542-f7l4ty2j 426 60 - - HYPH cord-002542-f7l4ty2j 426 61 RNAs rna NNS cord-002542-f7l4ty2j 426 62 observed observe VBD cord-002542-f7l4ty2j 426 63 here here RB cord-002542-f7l4ty2j 426 64 including include VBG cord-002542-f7l4ty2j 426 65 the the DT cord-002542-f7l4ty2j 426 66 complex complex JJ cord-002542-f7l4ty2j 426 67 rearrangements rearrangement NNS cord-002542-f7l4ty2j 426 68 observed observe VBN cord-002542-f7l4ty2j 426 69 for for IN cord-002542-f7l4ty2j 426 70 RNA1 RNA1 NNP cord-002542-f7l4ty2j 426 71 . . . cord-002542-f7l4ty2j 427 1 A a DT cord-002542-f7l4ty2j 427 2 defective defective JJ cord-002542-f7l4ty2j 427 3 - - HYPH cord-002542-f7l4ty2j 427 4 interfering interfere VBG cord-002542-f7l4ty2j 427 5 RNA RNA NNP cord-002542-f7l4ty2j 427 6 is be VBZ cord-002542-f7l4ty2j 427 7 a a DT cord-002542-f7l4ty2j 427 8 defective defective JJ cord-002542-f7l4ty2j 427 9 RNA RNA NNP cord-002542-f7l4ty2j 427 10 that that WDT cord-002542-f7l4ty2j 427 11 has have VBZ cord-002542-f7l4ty2j 427 12 the the DT cord-002542-f7l4ty2j 427 13 ability ability NN cord-002542-f7l4ty2j 427 14 to to TO cord-002542-f7l4ty2j 427 15 compete compete VB cord-002542-f7l4ty2j 427 16 with with IN cord-002542-f7l4ty2j 427 17 or or CC cord-002542-f7l4ty2j 427 18 otherwise otherwise RB cord-002542-f7l4ty2j 427 19 attenuate attenuate VB cord-002542-f7l4ty2j 427 20 the the DT cord-002542-f7l4ty2j 427 21 replication replication NN cord-002542-f7l4ty2j 427 22 and and CC cord-002542-f7l4ty2j 427 23 proliferation proliferation NN cord-002542-f7l4ty2j 427 24 of of IN cord-002542-f7l4ty2j 427 25 the the DT cord-002542-f7l4ty2j 427 26 wild wild JJ cord-002542-f7l4ty2j 427 27 - - HYPH cord-002542-f7l4ty2j 427 28 type type NN cord-002542-f7l4ty2j 427 29 helper helper NN cord-002542-f7l4ty2j 427 30 virus virus NN cord-002542-f7l4ty2j 427 31 . . . cord-002542-f7l4ty2j 428 1 In in IN cord-002542-f7l4ty2j 428 2 our -PRON- PRP$ cord-002542-f7l4ty2j 428 3 study study NN cord-002542-f7l4ty2j 428 4 we -PRON- PRP cord-002542-f7l4ty2j 428 5 demonstrate demonstrate VBP cord-002542-f7l4ty2j 428 6 that that IN cord-002542-f7l4ty2j 428 7 the the DT cord-002542-f7l4ty2j 428 8 viral viral JJ cord-002542-f7l4ty2j 428 9 swarm swarm NNS cord-002542-f7l4ty2j 428 10 , , , cord-002542-f7l4ty2j 428 11 even even RB cord-002542-f7l4ty2j 428 12 after after IN cord-002542-f7l4ty2j 428 13 only only RB cord-002542-f7l4ty2j 428 14 a a DT cord-002542-f7l4ty2j 428 15 few few JJ cord-002542-f7l4ty2j 428 16 passages passage NNS cord-002542-f7l4ty2j 428 17 , , , cord-002542-f7l4ty2j 428 18 is be VBZ cord-002542-f7l4ty2j 428 19 replete replete JJ cord-002542-f7l4ty2j 428 20 with with IN cord-002542-f7l4ty2j 428 21 many many JJ cord-002542-f7l4ty2j 428 22 varieties variety NNS cord-002542-f7l4ty2j 428 23 of of IN cord-002542-f7l4ty2j 428 24 defective defective JJ cord-002542-f7l4ty2j 428 25 RNAs rna NNS cord-002542-f7l4ty2j 428 26 . . . cord-002542-f7l4ty2j 429 1 With with IN cord-002542-f7l4ty2j 429 2 a a DT cord-002542-f7l4ty2j 429 3 single single JJ cord-002542-f7l4ty2j 429 4 sequencing sequencing NN cord-002542-f7l4ty2j 429 5 experiment experiment NN cord-002542-f7l4ty2j 429 6 , , , cord-002542-f7l4ty2j 429 7 we -PRON- PRP cord-002542-f7l4ty2j 429 8 would would MD cord-002542-f7l4ty2j 429 9 not not RB cord-002542-f7l4ty2j 429 10 be be VB cord-002542-f7l4ty2j 429 11 able able JJ cord-002542-f7l4ty2j 429 12 to to TO cord-002542-f7l4ty2j 429 13 determine determine VB cord-002542-f7l4ty2j 429 14 whether whether IN cord-002542-f7l4ty2j 429 15 these these DT cord-002542-f7l4ty2j 429 16 defective defective JJ cord-002542-f7l4ty2j 429 17 RNAs rna NNS cord-002542-f7l4ty2j 429 18 are be VBP cord-002542-f7l4ty2j 429 19 accumulating accumulate VBG cord-002542-f7l4ty2j 429 20 , , , cord-002542-f7l4ty2j 429 21 diminishing diminish VBG cord-002542-f7l4ty2j 429 22 or or CC cord-002542-f7l4ty2j 429 23 make make VB cord-002542-f7l4ty2j 429 24 - - HYPH cord-002542-f7l4ty2j 429 25 up up RP cord-002542-f7l4ty2j 429 26 a a DT cord-002542-f7l4ty2j 429 27 static static JJ cord-002542-f7l4ty2j 429 28 component component NN cord-002542-f7l4ty2j 429 29 of of IN cord-002542-f7l4ty2j 429 30 the the DT cord-002542-f7l4ty2j 429 31 viral viral JJ cord-002542-f7l4ty2j 429 32 quasi quasi JJ cord-002542-f7l4ty2j 429 33 - - NNS cord-002542-f7l4ty2j 429 34 species specie NNS cord-002542-f7l4ty2j 429 35 . . . cord-002542-f7l4ty2j 430 1 However however RB cord-002542-f7l4ty2j 430 2 , , , cord-002542-f7l4ty2j 430 3 as as IN cord-002542-f7l4ty2j 430 4 we -PRON- PRP cord-002542-f7l4ty2j 430 5 perform perform VBP cord-002542-f7l4ty2j 430 6 serial serial JJ cord-002542-f7l4ty2j 430 7 passaging passaging NN cord-002542-f7l4ty2j 430 8 with with IN cord-002542-f7l4ty2j 430 9 sequential sequential JJ cord-002542-f7l4ty2j 430 10 sequencing sequencing NN cord-002542-f7l4ty2j 430 11 experiments experiment NNS cord-002542-f7l4ty2j 430 12 , , , cord-002542-f7l4ty2j 430 13 we -PRON- PRP cord-002542-f7l4ty2j 430 14 can can MD cord-002542-f7l4ty2j 430 15 determine determine VB cord-002542-f7l4ty2j 430 16 which which WDT cord-002542-f7l4ty2j 430 17 defective defective JJ cord-002542-f7l4ty2j 430 18 RNAs rna NNS cord-002542-f7l4ty2j 430 19 are be VBP cord-002542-f7l4ty2j 430 20 accumulating accumulate VBG cord-002542-f7l4ty2j 430 21 ( ( -LRB- cord-002542-f7l4ty2j 430 22 for for IN cord-002542-f7l4ty2j 430 23 example example NN cord-002542-f7l4ty2j 430 24 the the DT cord-002542-f7l4ty2j 430 25 ' ' `` cord-002542-f7l4ty2j 430 26 mature mature JJ cord-002542-f7l4ty2j 430 27 ' ' '' cord-002542-f7l4ty2j 430 28 DI di NN cord-002542-f7l4ty2j 430 29 - - HYPH cord-002542-f7l4ty2j 430 30 RNAs RNAs NNPS cord-002542-f7l4ty2j 430 31 ) ) -RRB- cord-002542-f7l4ty2j 430 32 and and CC cord-002542-f7l4ty2j 430 33 which which WDT cord-002542-f7l4ty2j 430 34 are be VBP cord-002542-f7l4ty2j 430 35 not not RB cord-002542-f7l4ty2j 430 36 ( ( -LRB- cord-002542-f7l4ty2j 430 37 e.g. e.g. RB cord-002542-f7l4ty2j 430 38 the the DT cord-002542-f7l4ty2j 430 39 putative putative JJ cord-002542-f7l4ty2j 430 40 intermediate intermediate NN cord-002542-f7l4ty2j 430 41 , , , cord-002542-f7l4ty2j 430 42 or or CC cord-002542-f7l4ty2j 430 43 ' ' `` cord-002542-f7l4ty2j 430 44 immature immature JJ cord-002542-f7l4ty2j 430 45 ' ' '' cord-002542-f7l4ty2j 430 46 defective defective JJ cord-002542-f7l4ty2j 430 47 RNAs rna NNS cord-002542-f7l4ty2j 430 48 ) ) -RRB- cord-002542-f7l4ty2j 430 49 . . . cord-002542-f7l4ty2j 431 1 It -PRON- PRP cord-002542-f7l4ty2j 431 2 would would MD cord-002542-f7l4ty2j 431 3 be be VB cord-002542-f7l4ty2j 431 4 impractical impractical JJ cord-002542-f7l4ty2j 431 5 to to TO cord-002542-f7l4ty2j 431 6 validate validate VB cord-002542-f7l4ty2j 431 7 each each DT cord-002542-f7l4ty2j 431 8 of of IN cord-002542-f7l4ty2j 431 9 the the DT cord-002542-f7l4ty2j 431 10 many many JJ cord-002542-f7l4ty2j 431 11 hundreds hundred NNS cord-002542-f7l4ty2j 431 12 of of IN cord-002542-f7l4ty2j 431 13 detected detect VBN cord-002542-f7l4ty2j 431 14 defective defective JJ cord-002542-f7l4ty2j 431 15 RNA RNA NNP cord-002542-f7l4ty2j 431 16 species specie NNS cord-002542-f7l4ty2j 431 17 with with IN cord-002542-f7l4ty2j 431 18 molecular molecular JJ cord-002542-f7l4ty2j 431 19 virological virological JJ cord-002542-f7l4ty2j 431 20 experiments experiment NNS cord-002542-f7l4ty2j 431 21 to to TO cord-002542-f7l4ty2j 431 22 determine determine VB cord-002542-f7l4ty2j 431 23 whether whether IN cord-002542-f7l4ty2j 431 24 they -PRON- PRP cord-002542-f7l4ty2j 431 25 truly truly RB cord-002542-f7l4ty2j 431 26 can can MD cord-002542-f7l4ty2j 431 27 attenuate attenuate VB cord-002542-f7l4ty2j 431 28 or or CC cord-002542-f7l4ty2j 431 29 interfere interfere VB cord-002542-f7l4ty2j 431 30 with with IN cord-002542-f7l4ty2j 431 31 wild wild JJ cord-002542-f7l4ty2j 431 32 - - HYPH cord-002542-f7l4ty2j 431 33 type type NN cord-002542-f7l4ty2j 431 34 virus virus NN cord-002542-f7l4ty2j 431 35 replication replication NN cord-002542-f7l4ty2j 431 36 and and CC cord-002542-f7l4ty2j 431 37 to to TO cord-002542-f7l4ty2j 431 38 therefore therefore RB cord-002542-f7l4ty2j 431 39 categorize categorize VB cord-002542-f7l4ty2j 431 40 that that DT cord-002542-f7l4ty2j 431 41 species specie NNS cord-002542-f7l4ty2j 431 42 as as IN cord-002542-f7l4ty2j 431 43 a a DT cord-002542-f7l4ty2j 431 44 defective defective JJ cord-002542-f7l4ty2j 431 45 - - HYPH cord-002542-f7l4ty2j 431 46 interfering interfere VBG cord-002542-f7l4ty2j 431 47 RNA RNA NNP cord-002542-f7l4ty2j 431 48 . . . cord-002542-f7l4ty2j 432 1 Indeed indeed RB cord-002542-f7l4ty2j 432 2 , , , cord-002542-f7l4ty2j 432 3 we -PRON- PRP cord-002542-f7l4ty2j 432 4 can can MD cord-002542-f7l4ty2j 432 5 not not RB cord-002542-f7l4ty2j 432 6 exclude exclude VB cord-002542-f7l4ty2j 432 7 the the DT cord-002542-f7l4ty2j 432 8 possibility possibility NN cord-002542-f7l4ty2j 432 9 that that IN cord-002542-f7l4ty2j 432 10 multiple multiple JJ cord-002542-f7l4ty2j 432 11 DI DI NNP cord-002542-f7l4ty2j 432 12 - - HYPH cord-002542-f7l4ty2j 432 13 R R NNP cord-002542-f7l4ty2j 432 14 - - HYPH cord-002542-f7l4ty2j 432 15 NAs NAs NNP cord-002542-f7l4ty2j 432 16 act act NNP cord-002542-f7l4ty2j 432 17 co co NNP cord-002542-f7l4ty2j 432 18 - - NN cord-002542-f7l4ty2j 432 19 operatively operatively RB cord-002542-f7l4ty2j 432 20 within within IN cord-002542-f7l4ty2j 432 21 the the DT cord-002542-f7l4ty2j 432 22 viral viral JJ cord-002542-f7l4ty2j 432 23 quasi quasi JJ cord-002542-f7l4ty2j 432 24 - - HYPH cord-002542-f7l4ty2j 432 25 species specie NNS cord-002542-f7l4ty2j 432 26 and and CC cord-002542-f7l4ty2j 432 27 are be VBP cord-002542-f7l4ty2j 432 28 mutually mutually RB cord-002542-f7l4ty2j 432 29 dependent dependent JJ cord-002542-f7l4ty2j 432 30 upon upon IN cord-002542-f7l4ty2j 432 31 one one CD cord-002542-f7l4ty2j 432 32 another another DT cord-002542-f7l4ty2j 432 33 . . . cord-002542-f7l4ty2j 433 1 However however RB cord-002542-f7l4ty2j 433 2 , , , cord-002542-f7l4ty2j 433 3 the the DT cord-002542-f7l4ty2j 433 4 demonstration demonstration NN cord-002542-f7l4ty2j 433 5 here here RB cord-002542-f7l4ty2j 433 6 of of IN cord-002542-f7l4ty2j 433 7 an an DT cord-002542-f7l4ty2j 433 8 accumulation accumulation NN cord-002542-f7l4ty2j 433 9 during during IN cord-002542-f7l4ty2j 433 10 serial serial JJ cord-002542-f7l4ty2j 433 11 passaging passaging NN cord-002542-f7l4ty2j 433 12 is be VBZ cord-002542-f7l4ty2j 433 13 strong strong JJ cord-002542-f7l4ty2j 433 14 evidence evidence NN cord-002542-f7l4ty2j 433 15 that that IN cord-002542-f7l4ty2j 433 16 these these DT cord-002542-f7l4ty2j 433 17 species specie NNS cord-002542-f7l4ty2j 433 18 are be VBP cord-002542-f7l4ty2j 433 19 interfering interfere VBG cord-002542-f7l4ty2j 433 20 , , , cord-002542-f7l4ty2j 433 21 as as IN cord-002542-f7l4ty2j 433 22 their -PRON- PRP$ cord-002542-f7l4ty2j 433 23 accumulation accumulation NN cord-002542-f7l4ty2j 433 24 essentially essentially RB cord-002542-f7l4ty2j 433 25 dilutes dilute VBZ cord-002542-f7l4ty2j 433 26 the the DT cord-002542-f7l4ty2j 433 27 pool pool NN cord-002542-f7l4ty2j 433 28 of of IN cord-002542-f7l4ty2j 433 29 wild wild JJ cord-002542-f7l4ty2j 433 30 - - HYPH cord-002542-f7l4ty2j 433 31 type type NN cord-002542-f7l4ty2j 433 32 functional functional JJ cord-002542-f7l4ty2j 433 33 virus virus NN cord-002542-f7l4ty2j 433 34 . . . cord-002542-f7l4ty2j 434 1 With with IN cord-002542-f7l4ty2j 434 2 this this DT cord-002542-f7l4ty2j 434 3 in in IN cord-002542-f7l4ty2j 434 4 mind mind NN cord-002542-f7l4ty2j 434 5 , , , cord-002542-f7l4ty2j 434 6 we -PRON- PRP cord-002542-f7l4ty2j 434 7 believe believe VBP cord-002542-f7l4ty2j 434 8 it -PRON- PRP cord-002542-f7l4ty2j 434 9 would would MD cord-002542-f7l4ty2j 434 10 be be VB cord-002542-f7l4ty2j 434 11 suitable suitable JJ cord-002542-f7l4ty2j 434 12 to to TO cord-002542-f7l4ty2j 434 13 describe describe VB cord-002542-f7l4ty2j 434 14 the the DT cord-002542-f7l4ty2j 434 15 mature mature JJ cord-002542-f7l4ty2j 434 16 defective defective JJ cord-002542-f7l4ty2j 434 17 RNAs rna NNS cord-002542-f7l4ty2j 434 18 as as IN cord-002542-f7l4ty2j 434 19 defective defective JJ cord-002542-f7l4ty2j 434 20 - - HYPH cord-002542-f7l4ty2j 434 21 interfering interfere VBG cord-002542-f7l4ty2j 434 22 RNAs rna NNS cord-002542-f7l4ty2j 434 23 ( ( -LRB- cord-002542-f7l4ty2j 434 24 DI DI NNP cord-002542-f7l4ty2j 434 25 - - HYPH cord-002542-f7l4ty2j 434 26 RNAs RNAs NNPS cord-002542-f7l4ty2j 434 27 ) ) -RRB- cord-002542-f7l4ty2j 434 28 , , , cord-002542-f7l4ty2j 434 29 and and CC cord-002542-f7l4ty2j 434 30 the the DT cord-002542-f7l4ty2j 434 31 ' ' `` cord-002542-f7l4ty2j 434 32 immature immature JJ cord-002542-f7l4ty2j 434 33 ' ' '' cord-002542-f7l4ty2j 434 34 only only RB cord-002542-f7l4ty2j 434 35 as as IN cord-002542-f7l4ty2j 434 36 defective defective JJ cord-002542-f7l4ty2j 434 37 RNAs rna NNS cord-002542-f7l4ty2j 434 38 . . . cord-002542-f7l4ty2j 435 1 It -PRON- PRP cord-002542-f7l4ty2j 435 2 is be VBZ cord-002542-f7l4ty2j 435 3 remarkable remarkable JJ cord-002542-f7l4ty2j 435 4 that that IN cord-002542-f7l4ty2j 435 5 FHV FHV NNP cord-002542-f7l4ty2j 435 6 is be VBZ cord-002542-f7l4ty2j 435 7 able able JJ cord-002542-f7l4ty2j 435 8 to to TO cord-002542-f7l4ty2j 435 9 maintain maintain VB cord-002542-f7l4ty2j 435 10 a a DT cord-002542-f7l4ty2j 435 11 viable viable JJ cord-002542-f7l4ty2j 435 12 infection infection NN cord-002542-f7l4ty2j 435 13 despite despite IN cord-002542-f7l4ty2j 435 14 being be VBG cord-002542-f7l4ty2j 435 15 burdened burden VBN cord-002542-f7l4ty2j 435 16 with with IN cord-002542-f7l4ty2j 435 17 such such PDT cord-002542-f7l4ty2j 435 18 a a DT cord-002542-f7l4ty2j 435 19 gross gross JJ cord-002542-f7l4ty2j 435 20 excess excess NN cord-002542-f7l4ty2j 435 21 of of IN cord-002542-f7l4ty2j 435 22 DI DI NNP cord-002542-f7l4ty2j 435 23 - - HYPH cord-002542-f7l4ty2j 435 24 RNAs rna NNS cord-002542-f7l4ty2j 435 25 in in IN cord-002542-f7l4ty2j 435 26 the the DT cord-002542-f7l4ty2j 435 27 final final JJ cord-002542-f7l4ty2j 435 28 passages passage NNS cord-002542-f7l4ty2j 435 29 presented present VBN cord-002542-f7l4ty2j 435 30 here here RB cord-002542-f7l4ty2j 435 31 . . . cord-002542-f7l4ty2j 436 1 By by IN cord-002542-f7l4ty2j 436 2 performing perform VBG cord-002542-f7l4ty2j 436 3 TCID50 TCID50 NNP cord-002542-f7l4ty2j 436 4 assays assay NNS cord-002542-f7l4ty2j 436 5 of of IN cord-002542-f7l4ty2j 436 6 the the DT cord-002542-f7l4ty2j 436 7 original original JJ cord-002542-f7l4ty2j 436 8 inocula inocula NN cord-002542-f7l4ty2j 436 9 used use VBN cord-002542-f7l4ty2j 436 10 between between IN cord-002542-f7l4ty2j 436 11 each each DT cord-002542-f7l4ty2j 436 12 of of IN cord-002542-f7l4ty2j 436 13 the the DT cord-002542-f7l4ty2j 436 14 passages passage NNS cord-002542-f7l4ty2j 436 15 and and CC cord-002542-f7l4ty2j 436 16 of of IN cord-002542-f7l4ty2j 436 17 the the DT cord-002542-f7l4ty2j 436 18 particles particle NNS cord-002542-f7l4ty2j 436 19 purified purify VBN cord-002542-f7l4ty2j 436 20 from from IN cord-002542-f7l4ty2j 436 21 each each DT cord-002542-f7l4ty2j 436 22 passage passage NN cord-002542-f7l4ty2j 436 23 , , , cord-002542-f7l4ty2j 436 24 we -PRON- PRP cord-002542-f7l4ty2j 436 25 show show VBP cord-002542-f7l4ty2j 436 26 that that IN cord-002542-f7l4ty2j 436 27 there there EX cord-002542-f7l4ty2j 436 28 is be VBZ cord-002542-f7l4ty2j 436 29 a a DT cord-002542-f7l4ty2j 436 30 dramatic dramatic JJ cord-002542-f7l4ty2j 436 31 reduction reduction NN cord-002542-f7l4ty2j 436 32 in in IN cord-002542-f7l4ty2j 436 33 specific specific JJ cord-002542-f7l4ty2j 436 34 infectivity infectivity NN cord-002542-f7l4ty2j 436 35 during during IN cord-002542-f7l4ty2j 436 36 passaging passaging NN cord-002542-f7l4ty2j 436 37 corresponding correspond VBG cord-002542-f7l4ty2j 436 38 with with IN cord-002542-f7l4ty2j 436 39 the the DT cord-002542-f7l4ty2j 436 40 increase increase NN cord-002542-f7l4ty2j 436 41 in in IN cord-002542-f7l4ty2j 436 42 the the DT cord-002542-f7l4ty2j 436 43 DI DI NNP cord-002542-f7l4ty2j 436 44 - - HYPH cord-002542-f7l4ty2j 436 45 RNA RNA NNP cord-002542-f7l4ty2j 436 46 content content NN cord-002542-f7l4ty2j 436 47 . . . cord-002542-f7l4ty2j 437 1 DI DI NNP cord-002542-f7l4ty2j 437 2 - - HYPH cord-002542-f7l4ty2j 437 3 RNAs rna NNS cord-002542-f7l4ty2j 437 4 have have VBP cord-002542-f7l4ty2j 437 5 generally generally RB cord-002542-f7l4ty2j 437 6 been be VBN cord-002542-f7l4ty2j 437 7 demonstrated demonstrate VBN cord-002542-f7l4ty2j 437 8 to to TO cord-002542-f7l4ty2j 437 9 arise arise VB cord-002542-f7l4ty2j 437 10 at at IN cord-002542-f7l4ty2j 437 11 high high JJ cord-002542-f7l4ty2j 437 12 MOIs mois NN cord-002542-f7l4ty2j 437 13 , , , cord-002542-f7l4ty2j 437 14 as as IN cord-002542-f7l4ty2j 437 15 was be VBD cord-002542-f7l4ty2j 437 16 the the DT cord-002542-f7l4ty2j 437 17 scenario scenario NN cord-002542-f7l4ty2j 437 18 with with IN cord-002542-f7l4ty2j 437 19 our -PRON- PRP$ cord-002542-f7l4ty2j 437 20 first first JJ cord-002542-f7l4ty2j 437 21 passages passage NNS cord-002542-f7l4ty2j 437 22 . . . cord-002542-f7l4ty2j 438 1 However however RB cord-002542-f7l4ty2j 438 2 , , , cord-002542-f7l4ty2j 438 3 our -PRON- PRP$ cord-002542-f7l4ty2j 438 4 calculated calculate VBN cord-002542-f7l4ty2j 438 5 MOI MOI NNP cord-002542-f7l4ty2j 438 6 drops drop VBZ cord-002542-f7l4ty2j 438 7 rapidly rapidly RB cord-002542-f7l4ty2j 438 8 after after IN cord-002542-f7l4ty2j 438 9 DI DI NNP cord-002542-f7l4ty2j 438 10 - - HYPH cord-002542-f7l4ty2j 438 11 RNAs rna NNS cord-002542-f7l4ty2j 438 12 have have VBP cord-002542-f7l4ty2j 438 13 formed form VBN cord-002542-f7l4ty2j 438 14 to to IN cord-002542-f7l4ty2j 438 15 levels level NNS cord-002542-f7l4ty2j 438 16 that that WDT cord-002542-f7l4ty2j 438 17 might may MD cord-002542-f7l4ty2j 438 18 be be VB cord-002542-f7l4ty2j 438 19 expected expect VBN cord-002542-f7l4ty2j 438 20 during during IN cord-002542-f7l4ty2j 438 21 typical typical JJ cord-002542-f7l4ty2j 438 22 in in IN cord-002542-f7l4ty2j 438 23 vivo vivo FW cord-002542-f7l4ty2j 438 24 viral viral JJ cord-002542-f7l4ty2j 438 25 passaging passaging NN cord-002542-f7l4ty2j 438 26 scenarios scenario NNS cord-002542-f7l4ty2j 438 27 . . . cord-002542-f7l4ty2j 439 1 However however RB cord-002542-f7l4ty2j 439 2 , , , cord-002542-f7l4ty2j 439 3 in in IN cord-002542-f7l4ty2j 439 4 this this DT cord-002542-f7l4ty2j 439 5 experiment experiment NN cord-002542-f7l4ty2j 439 6 we -PRON- PRP cord-002542-f7l4ty2j 439 7 were be VBD cord-002542-f7l4ty2j 439 8 actually actually RB cord-002542-f7l4ty2j 439 9 passaging passage VBG cord-002542-f7l4ty2j 439 10 a a DT cord-002542-f7l4ty2j 439 11 large large JJ cord-002542-f7l4ty2j 439 12 number number NN cord-002542-f7l4ty2j 439 13 of of IN cord-002542-f7l4ty2j 439 14 virus virus NN cord-002542-f7l4ty2j 439 15 particles particle NNS cord-002542-f7l4ty2j 439 16 between between IN cord-002542-f7l4ty2j 439 17 cells cell NNS cord-002542-f7l4ty2j 439 18 , , , cord-002542-f7l4ty2j 439 19 but but CC cord-002542-f7l4ty2j 439 20 with with IN cord-002542-f7l4ty2j 439 21 a a DT cord-002542-f7l4ty2j 439 22 low low JJ cord-002542-f7l4ty2j 439 23 specific specific JJ cord-002542-f7l4ty2j 439 24 infectivity infectivity NN cord-002542-f7l4ty2j 439 25 . . . cord-002542-f7l4ty2j 440 1 It -PRON- PRP cord-002542-f7l4ty2j 440 2 is be VBZ cord-002542-f7l4ty2j 440 3 also also RB cord-002542-f7l4ty2j 440 4 interesting interesting JJ cord-002542-f7l4ty2j 440 5 to to TO cord-002542-f7l4ty2j 440 6 observe observe VB cord-002542-f7l4ty2j 440 7 that that DT cord-002542-f7l4ty2j 440 8 for for IN cord-002542-f7l4ty2j 440 9 the the DT cord-002542-f7l4ty2j 440 10 final final JJ cord-002542-f7l4ty2j 440 11 passages passage NNS cord-002542-f7l4ty2j 440 12 there there EX cord-002542-f7l4ty2j 440 13 appears appear VBZ cord-002542-f7l4ty2j 440 14 to to TO cord-002542-f7l4ty2j 440 15 be be VB cord-002542-f7l4ty2j 440 16 a a DT cord-002542-f7l4ty2j 440 17 protective protective JJ cord-002542-f7l4ty2j 440 18 property property NN cord-002542-f7l4ty2j 440 19 of of IN cord-002542-f7l4ty2j 440 20 the the DT cord-002542-f7l4ty2j 440 21 DI DI NNP cord-002542-f7l4ty2j 440 22 - - HYPH cord-002542-f7l4ty2j 440 23 RNAs rna NNS cord-002542-f7l4ty2j 440 24 as as IN cord-002542-f7l4ty2j 440 25 determined determine VBN cord-002542-f7l4ty2j 440 26 by by IN cord-002542-f7l4ty2j 440 27 flow flow NN cord-002542-f7l4ty2j 440 28 - - HYPH cord-002542-f7l4ty2j 440 29 cytometry cytometry NN cord-002542-f7l4ty2j 440 30 , , , cord-002542-f7l4ty2j 440 31 but but CC cord-002542-f7l4ty2j 440 32 only only RB cord-002542-f7l4ty2j 440 33 when when WRB cord-002542-f7l4ty2j 440 34 administered administer VBN cord-002542-f7l4ty2j 440 35 at at IN cord-002542-f7l4ty2j 440 36 the the DT cord-002542-f7l4ty2j 440 37 highest high JJS cord-002542-f7l4ty2j 440 38 doses dose NNS cord-002542-f7l4ty2j 440 39 corresponding correspond VBG cord-002542-f7l4ty2j 440 40 to to IN cord-002542-f7l4ty2j 440 41 over~30,000 over~30,000 NNP cord-002542-f7l4ty2j 440 42 particles particle NNS cord-002542-f7l4ty2j 440 43 per per IN cord-002542-f7l4ty2j 440 44 cell cell NN cord-002542-f7l4ty2j 440 45 . . . cord-002542-f7l4ty2j 441 1 However however RB cord-002542-f7l4ty2j 441 2 , , , cord-002542-f7l4ty2j 441 3 the the DT cord-002542-f7l4ty2j 441 4 role role NN cord-002542-f7l4ty2j 441 5 that that WDT cord-002542-f7l4ty2j 441 6 DI DI NNP cord-002542-f7l4ty2j 441 7 - - HYPH cord-002542-f7l4ty2j 441 8 RNAs rna NNS cord-002542-f7l4ty2j 441 9 might may MD cord-002542-f7l4ty2j 441 10 play play VB cord-002542-f7l4ty2j 441 11 in in IN cord-002542-f7l4ty2j 441 12 vivo vivo NN cord-002542-f7l4ty2j 441 13 is be VBZ cord-002542-f7l4ty2j 441 14 not not RB cord-002542-f7l4ty2j 441 15 clear clear JJ cord-002542-f7l4ty2j 441 16 , , , cord-002542-f7l4ty2j 441 17 as as IN cord-002542-f7l4ty2j 441 18 these these DT cord-002542-f7l4ty2j 441 19 very very RB cord-002542-f7l4ty2j 441 20 high high JJ cord-002542-f7l4ty2j 441 21 doses dose NNS cord-002542-f7l4ty2j 441 22 may may MD cord-002542-f7l4ty2j 441 23 not not RB cord-002542-f7l4ty2j 441 24 be be VB cord-002542-f7l4ty2j 441 25 physiologically physiologically RB cord-002542-f7l4ty2j 441 26 relevant relevant JJ cord-002542-f7l4ty2j 441 27 . . . cord-002542-f7l4ty2j 442 1 DI DI NNP cord-002542-f7l4ty2j 442 2 - - HYPH cord-002542-f7l4ty2j 442 3 RNAs rna NNS cord-002542-f7l4ty2j 442 4 for for IN cord-002542-f7l4ty2j 442 5 FHV FHV NNP cord-002542-f7l4ty2j 442 6 similar similar JJ cord-002542-f7l4ty2j 442 7 to to IN cord-002542-f7l4ty2j 442 8 the the DT cord-002542-f7l4ty2j 442 9 ones one NNS cord-002542-f7l4ty2j 442 10 described describe VBN cord-002542-f7l4ty2j 442 11 here here RB cord-002542-f7l4ty2j 442 12 have have VBP cord-002542-f7l4ty2j 442 13 been be VBN cord-002542-f7l4ty2j 442 14 observed observe VBN cord-002542-f7l4ty2j 442 15 to to TO cord-002542-f7l4ty2j 442 16 arise arise VB cord-002542-f7l4ty2j 442 17 in in IN cord-002542-f7l4ty2j 442 18 experimental experimental JJ cord-002542-f7l4ty2j 442 19 fruit fruit NN cord-002542-f7l4ty2j 442 20 fly fly VBP cord-002542-f7l4ty2j 442 21 infections infection NNS cord-002542-f7l4ty2j 442 22 [ [ -LRB- cord-002542-f7l4ty2j 442 23 33 33 CD cord-002542-f7l4ty2j 442 24 ] ] -RRB- cord-002542-f7l4ty2j 442 25 and and CC cord-002542-f7l4ty2j 442 26 so so RB cord-002542-f7l4ty2j 442 27 the the DT cord-002542-f7l4ty2j 442 28 mechanism mechanism NN cord-002542-f7l4ty2j 442 29 of of IN cord-002542-f7l4ty2j 442 30 formation formation NN cord-002542-f7l4ty2j 442 31 and/or and/or CC cord-002542-f7l4ty2j 442 32 selection selection NN cord-002542-f7l4ty2j 442 33 is be VBZ cord-002542-f7l4ty2j 442 34 likely likely JJ cord-002542-f7l4ty2j 442 35 to to TO cord-002542-f7l4ty2j 442 36 be be VB cord-002542-f7l4ty2j 442 37 similar similar JJ cord-002542-f7l4ty2j 442 38 in in IN cord-002542-f7l4ty2j 442 39 cell cell NN cord-002542-f7l4ty2j 442 40 culture culture NN cord-002542-f7l4ty2j 442 41 and and CC cord-002542-f7l4ty2j 442 42 in in IN cord-002542-f7l4ty2j 442 43 vivo vivo NNP cord-002542-f7l4ty2j 442 44 . . . cord-002542-f7l4ty2j 443 1 However however RB cord-002542-f7l4ty2j 443 2 , , , cord-002542-f7l4ty2j 443 3 whether whether IN cord-002542-f7l4ty2j 443 4 RNA RNA NNP cord-002542-f7l4ty2j 443 5 viruses virus NNS cord-002542-f7l4ty2j 443 6 such such JJ cord-002542-f7l4ty2j 443 7 as as IN cord-002542-f7l4ty2j 443 8 FHV FHV NNP cord-002542-f7l4ty2j 443 9 have have VBP cord-002542-f7l4ty2j 443 10 evolved evolve VBN cord-002542-f7l4ty2j 443 11 to to TO cord-002542-f7l4ty2j 443 12 favor favor VB cord-002542-f7l4ty2j 443 13 the the DT cord-002542-f7l4ty2j 443 14 spontaneous spontaneous JJ cord-002542-f7l4ty2j 443 15 formation formation NN cord-002542-f7l4ty2j 443 16 of of IN cord-002542-f7l4ty2j 443 17 DI DI NNP cord-002542-f7l4ty2j 443 18 - - HYPH cord-002542-f7l4ty2j 443 19 RNAs rna NNS cord-002542-f7l4ty2j 443 20 and and CC cord-002542-f7l4ty2j 443 21 if if IN cord-002542-f7l4ty2j 443 22 so so RB cord-002542-f7l4ty2j 443 23 whether whether IN cord-002542-f7l4ty2j 443 24 these these DT cord-002542-f7l4ty2j 443 25 DI DI NNP cord-002542-f7l4ty2j 443 26 - - HYPH cord-002542-f7l4ty2j 443 27 RNAs rna NNS cord-002542-f7l4ty2j 443 28 play play VBP cord-002542-f7l4ty2j 443 29 an an DT cord-002542-f7l4ty2j 443 30 important important JJ cord-002542-f7l4ty2j 443 31 role role NN cord-002542-f7l4ty2j 443 32 in in IN cord-002542-f7l4ty2j 443 33 modifying modify VBG cord-002542-f7l4ty2j 443 34 the the DT cord-002542-f7l4ty2j 443 35 life life NN cord-002542-f7l4ty2j 443 36 - - HYPH cord-002542-f7l4ty2j 443 37 cycle cycle NN cord-002542-f7l4ty2j 443 38 of of IN cord-002542-f7l4ty2j 443 39 the the DT cord-002542-f7l4ty2j 443 40 virus virus NN cord-002542-f7l4ty2j 443 41 , , , cord-002542-f7l4ty2j 443 42 is be VBZ cord-002542-f7l4ty2j 443 43 yet yet RB cord-002542-f7l4ty2j 443 44 to to TO cord-002542-f7l4ty2j 443 45 be be VB cord-002542-f7l4ty2j 443 46 determined determine VBN cord-002542-f7l4ty2j 443 47 . . . cord-002542-f7l4ty2j 444 1 and and CC cord-002542-f7l4ty2j 444 2 the the DT cord-002542-f7l4ty2j 444 3 stacked stacked JJ cord-002542-f7l4ty2j 444 4 frequencies frequency NNS cord-002542-f7l4ty2j 444 5 of of IN cord-002542-f7l4ty2j 444 6 each each DT cord-002542-f7l4ty2j 444 7 detected detect VBN cord-002542-f7l4ty2j 444 8 defective defective JJ cord-002542-f7l4ty2j 444 9 RNA RNA NNP cord-002542-f7l4ty2j 444 10 is be VBZ cord-002542-f7l4ty2j 444 11 shown show VBN cord-002542-f7l4ty2j 444 12 in in IN cord-002542-f7l4ty2j 444 13 the the DT cord-002542-f7l4ty2j 444 14 y y NN cord-002542-f7l4ty2j 444 15 - - HYPH cord-002542-f7l4ty2j 444 16 axis axis NN cord-002542-f7l4ty2j 444 17 . . . cord-002542-f7l4ty2j 445 1 Each each DT cord-002542-f7l4ty2j 445 2 noncontiguous noncontiguous JJ cord-002542-f7l4ty2j 445 3 color color NN cord-002542-f7l4ty2j 445 4 represents represent VBZ cord-002542-f7l4ty2j 445 5 a a DT cord-002542-f7l4ty2j 445 6 specific specific JJ cord-002542-f7l4ty2j 445 7 genome genome NN cord-002542-f7l4ty2j 445 8 characterized characterize VBN cord-002542-f7l4ty2j 445 9 by by IN cord-002542-f7l4ty2j 445 10 MinION MinION VBG cord-002542-f7l4ty2j 445 11 nanopore nanopore NNP cord-002542-f7l4ty2j 445 12 sequencing sequencing NN cord-002542-f7l4ty2j 445 13 . . . cord-002542-f7l4ty2j 446 1 Wild wild JJ cord-002542-f7l4ty2j 446 2 - - HYPH cord-002542-f7l4ty2j 446 3 type type NN cord-002542-f7l4ty2j 446 4 genomes genome NNS cord-002542-f7l4ty2j 446 5 are be VBP cord-002542-f7l4ty2j 446 6 colored color VBN cord-002542-f7l4ty2j 446 7 green green JJ cord-002542-f7l4ty2j 446 8 , , , cord-002542-f7l4ty2j 446 9 genomes genome NNS cord-002542-f7l4ty2j 446 10 with with IN cord-002542-f7l4ty2j 446 11 one one CD cord-002542-f7l4ty2j 446 12 deletion deletion NN cord-002542-f7l4ty2j 446 13 are be VBP cord-002542-f7l4ty2j 446 14 colored color VBN cord-002542-f7l4ty2j 446 15 in in IN cord-002542-f7l4ty2j 446 16 shades shade NNS cord-002542-f7l4ty2j 446 17 of of IN cord-002542-f7l4ty2j 446 18 blue blue JJ cord-002542-f7l4ty2j 446 19 , , , cord-002542-f7l4ty2j 446 20 and and CC cord-002542-f7l4ty2j 446 21 genomes genome NNS cord-002542-f7l4ty2j 446 22 with with IN cord-002542-f7l4ty2j 446 23 two two CD cord-002542-f7l4ty2j 446 24 or or CC cord-002542-f7l4ty2j 446 25 more more JJR cord-002542-f7l4ty2j 446 26 deletions deletion NNS cord-002542-f7l4ty2j 446 27 are be VBP cord-002542-f7l4ty2j 446 28 colored color VBN cord-002542-f7l4ty2j 446 29 in in IN cord-002542-f7l4ty2j 446 30 shades shade NNS cord-002542-f7l4ty2j 446 31 of of IN cord-002542-f7l4ty2j 446 32 oranges orange NNS cord-002542-f7l4ty2j 446 33 ( ( -LRB- cord-002542-f7l4ty2j 446 34 using use VBG cord-002542-f7l4ty2j 446 35 the the DT cord-002542-f7l4ty2j 446 36 same same JJ cord-002542-f7l4ty2j 446 37 color color NN cord-002542-f7l4ty2j 446 38 scheme scheme NN cord-002542-f7l4ty2j 446 39 as as IN cord-002542-f7l4ty2j 446 40 in in IN cord-002542-f7l4ty2j 446 41 Fig Fig NNP cord-002542-f7l4ty2j 446 42 5C 5c CD cord-002542-f7l4ty2j 446 43 ) ) -RRB- cord-002542-f7l4ty2j 446 44 . . . cord-002542-f7l4ty2j 446 45 _SP cord-002542-f7l4ty2j 447 1 Each each DT cord-002542-f7l4ty2j 447 2 passage passage NN cord-002542-f7l4ty2j 447 3 in in IN cord-002542-f7l4ty2j 447 4 each each DT cord-002542-f7l4ty2j 447 5 replicate replicate VBP cord-002542-f7l4ty2j 447 6 as as RB cord-002542-f7l4ty2j 447 7 well well RB cord-002542-f7l4ty2j 447 8 as as IN cord-002542-f7l4ty2j 447 9 the the DT cord-002542-f7l4ty2j 447 10 inoculum inoculum NN cord-002542-f7l4ty2j 447 11 is be VBZ cord-002542-f7l4ty2j 447 12 shown show VBN cord-002542-f7l4ty2j 447 13 . . . cord-002542-f7l4ty2j 448 1 Output output NN cord-002542-f7l4ty2j 448 2 format format NN cord-002542-f7l4ty2j 448 3 , , , cord-002542-f7l4ty2j 448 4 as as IN cord-002542-f7l4ty2j 448 5 described describe VBN cord-002542-f7l4ty2j 448 6 in in IN cord-002542-f7l4ty2j 448 7 Routh Routh NNP cord-002542-f7l4ty2j 448 8 et et NNP cord-002542-f7l4ty2j 448 9 al al NNP cord-002542-f7l4ty2j 448 10 . . . cord-002542-f7l4ty2j 449 1 [ [ -LRB- cord-002542-f7l4ty2j 449 2 32 32 CD cord-002542-f7l4ty2j 449 3 ] ] -RRB- cord-002542-f7l4ty2j 449 4 , , , cord-002542-f7l4ty2j 449 5 is be VBZ cord-002542-f7l4ty2j 449 6 given give VBN cord-002542-f7l4ty2j 449 7 as as IN cord-002542-f7l4ty2j 449 8 " " `` cord-002542-f7l4ty2j 449 9 DonorCoord_to_AcceptorCoord_#_Counts donorcoord_to_acceptorcoord_#_count NNS cord-002542-f7l4ty2j 449 10 " " '' cord-002542-f7l4ty2j 449 11 . . . cord-002542-f7l4ty2j 450 1 This this DT cord-002542-f7l4ty2j 450 2 is be VBZ cord-002542-f7l4ty2j 450 3 the the DT cord-002542-f7l4ty2j 450 4 raw raw JJ cord-002542-f7l4ty2j 450 5 data datum NNS cord-002542-f7l4ty2j 450 6 used use VBN cord-002542-f7l4ty2j 450 7 to to TO cord-002542-f7l4ty2j 450 8 populate populate VB cord-002542-f7l4ty2j 450 9 Table Table NNP cord-002542-f7l4ty2j 450 10 1 1 CD cord-002542-f7l4ty2j 450 11 and and CC cord-002542-f7l4ty2j 450 12 S1 S1 NNP cord-002542-f7l4ty2j 450 13 Table Table NNP cord-002542-f7l4ty2j 450 14 . . . cord-002542-f7l4ty2j 451 1 ( ( -LRB- cord-002542-f7l4ty2j 451 2 ZIP zip NN cord-002542-f7l4ty2j 451 3 ) ) -RRB- cord-002542-f7l4ty2j 451 4 S2 S2 NNP cord-002542-f7l4ty2j 451 5 Datafile Datafile NNP cord-002542-f7l4ty2j 451 6 . . . cord-002542-f7l4ty2j 452 1 Genomes genome NNS cord-002542-f7l4ty2j 452 2 characterized characterize VBN cord-002542-f7l4ty2j 452 3 by by IN cord-002542-f7l4ty2j 452 4 MinION MinION VBG cord-002542-f7l4ty2j 452 5 nanopore nanopore NNP cord-002542-f7l4ty2j 452 6 sequencing sequencing NN cord-002542-f7l4ty2j 452 7 . . . cord-002542-f7l4ty2j 453 1 Table table NN cord-002542-f7l4ty2j 453 2 reports report VBZ cord-002542-f7l4ty2j 453 3 the the DT cord-002542-f7l4ty2j 453 4 annotated annotate VBN cord-002542-f7l4ty2j 453 5 genomes genome NNS cord-002542-f7l4ty2j 453 6 ( ( -LRB- cord-002542-f7l4ty2j 453 7 wild wild JJ cord-002542-f7l4ty2j 453 8 - - HYPH cord-002542-f7l4ty2j 453 9 type type NN cord-002542-f7l4ty2j 453 10 or or CC cord-002542-f7l4ty2j 453 11 defective defective JJ cord-002542-f7l4ty2j 453 12 ) ) -RRB- cord-002542-f7l4ty2j 453 13 and and CC cord-002542-f7l4ty2j 453 14 the the DT cord-002542-f7l4ty2j 453 15 number number NN cord-002542-f7l4ty2j 453 16 of of IN cord-002542-f7l4ty2j 453 17 mapped map VBN cord-002542-f7l4ty2j 453 18 reads read VBZ cord-002542-f7l4ty2j 453 19 in in IN cord-002542-f7l4ty2j 453 20 each each DT cord-002542-f7l4ty2j 453 21 passage passage NN cord-002542-f7l4ty2j 453 22 . . . cord-002542-f7l4ty2j 454 1 This this DT cord-002542-f7l4ty2j 454 2 the the DT cord-002542-f7l4ty2j 454 3 raw raw JJ cord-002542-f7l4ty2j 454 4 data datum NNS cord-002542-f7l4ty2j 454 5 used use VBN cord-002542-f7l4ty2j 454 6 to to TO cord-002542-f7l4ty2j 454 7 populate populate VB cord-002542-f7l4ty2j 454 8 the the DT cord-002542-f7l4ty2j 454 9 stacked stack VBN cord-002542-f7l4ty2j 454 10 - - HYPH cord-002542-f7l4ty2j 454 11 area area NN cord-002542-f7l4ty2j 454 12 plots plot NNS cord-002542-f7l4ty2j 454 13 in in IN cord-002542-f7l4ty2j 454 14 Fig Fig NNP cord-002542-f7l4ty2j 454 15 6 6 CD cord-002542-f7l4ty2j 454 16 and and CC cord-002542-f7l4ty2j 454 17 S6 S6 NNP cord-002542-f7l4ty2j 454 18 Fig Fig NNP cord-002542-f7l4ty2j 454 19 . . . cord-002542-f7l4ty2j 454 20 _SP cord-002542-f7l4ty2j 455 1 ( ( -LRB- cord-002542-f7l4ty2j 455 2 XLSX XLSX NNP cord-002542-f7l4ty2j 455 3 ) ) -RRB- cord-002542-f7l4ty2j 455 4 _SP cord-002542-f7l4ty2j 456 1 Chimeric chimeric JJ cord-002542-f7l4ty2j 456 2 16S 16S NNP cord-002542-f7l4ty2j 456 3 rRNA rrna NN cord-002542-f7l4ty2j 456 4 sequence sequence NN cord-002542-f7l4ty2j 456 5 formation formation NN cord-002542-f7l4ty2j 456 6 and and CC cord-002542-f7l4ty2j 456 7 detection detection NN cord-002542-f7l4ty2j 456 8 in in IN cord-002542-f7l4ty2j 456 9 Sanger Sanger NNP cord-002542-f7l4ty2j 456 10 and and CC cord-002542-f7l4ty2j 456 11 454-pyrosequenced 454-pyrosequenced CD cord-002542-f7l4ty2j 456 12 PCR PCR NNP cord-002542-f7l4ty2j 456 13 amplicons amplicon NNS cord-002542-f7l4ty2j 457 1 Why why WRB cord-002542-f7l4ty2j 457 2 do do VBP cord-002542-f7l4ty2j 457 3 RNA RNA NNP cord-002542-f7l4ty2j 457 4 viruses virus NNS cord-002542-f7l4ty2j 457 5 recombine recombine VB cord-002542-f7l4ty2j 457 6 ? ? . cord-002542-f7l4ty2j 458 1 The the DT cord-002542-f7l4ty2j 458 2 mechanism mechanism NN cord-002542-f7l4ty2j 458 3 of of IN cord-002542-f7l4ty2j 458 4 RNA RNA NNP cord-002542-f7l4ty2j 458 5 recombination recombination NN cord-002542-f7l4ty2j 458 6 in in IN cord-002542-f7l4ty2j 458 7 poliovirus poliovirus NN cord-002542-f7l4ty2j 458 8 RNA RNA NNP cord-002542-f7l4ty2j 458 9 recombination recombination NN cord-002542-f7l4ty2j 458 10 in in IN cord-002542-f7l4ty2j 458 11 vivo vivo NN cord-002542-f7l4ty2j 458 12 in in IN cord-002542-f7l4ty2j 458 13 the the DT cord-002542-f7l4ty2j 458 14 absence absence NN cord-002542-f7l4ty2j 458 15 of of IN cord-002542-f7l4ty2j 458 16 viral viral JJ cord-002542-f7l4ty2j 458 17 replication replication NN cord-002542-f7l4ty2j 458 18 Sequencing sequencing NN cord-002542-f7l4ty2j 458 19 and and CC cord-002542-f7l4ty2j 458 20 analyses analysis NNS cord-002542-f7l4ty2j 458 21 of of IN cord-002542-f7l4ty2j 458 22 all all DT cord-002542-f7l4ty2j 458 23 known know VBN cord-002542-f7l4ty2j 458 24 human human JJ cord-002542-f7l4ty2j 458 25 rhinovirus rhinovirus NN cord-002542-f7l4ty2j 458 26 genomes genome NNS cord-002542-f7l4ty2j 458 27 reveal reveal VBP cord-002542-f7l4ty2j 458 28 structure structure NN cord-002542-f7l4ty2j 458 29 and and CC cord-002542-f7l4ty2j 458 30 evolution evolution NN cord-002542-f7l4ty2j 458 31 Widespread widespread JJ cord-002542-f7l4ty2j 458 32 intra intra JJ cord-002542-f7l4ty2j 458 33 - - JJ cord-002542-f7l4ty2j 458 34 serotype serotype JJ cord-002542-f7l4ty2j 458 35 recombination recombination NN cord-002542-f7l4ty2j 458 36 in in IN cord-002542-f7l4ty2j 458 37 natural natural JJ cord-002542-f7l4ty2j 458 38 populations population NNS cord-002542-f7l4ty2j 458 39 of of IN cord-002542-f7l4ty2j 458 40 dengue dengue NN cord-002542-f7l4ty2j 458 41 virus virus NN cord-002542-f7l4ty2j 458 42 Long long JJ cord-002542-f7l4ty2j 458 43 - - HYPH cord-002542-f7l4ty2j 458 44 term term NN cord-002542-f7l4ty2j 458 45 circulation circulation NN cord-002542-f7l4ty2j 458 46 of of IN cord-002542-f7l4ty2j 458 47 vaccine vaccine NN cord-002542-f7l4ty2j 458 48 - - HYPH cord-002542-f7l4ty2j 458 49 derived derive VBN cord-002542-f7l4ty2j 458 50 poliovirus poliovirus NN cord-002542-f7l4ty2j 458 51 that that WDT cord-002542-f7l4ty2j 458 52 causes cause VBZ cord-002542-f7l4ty2j 458 53 paralytic paralytic JJ cord-002542-f7l4ty2j 458 54 disease disease NN cord-002542-f7l4ty2j 458 55 Nucleotide nucleotide JJ cord-002542-f7l4ty2j 458 56 - - HYPH cord-002542-f7l4ty2j 458 57 resolution resolution NN cord-002542-f7l4ty2j 458 58 profiling profiling NN cord-002542-f7l4ty2j 458 59 of of IN cord-002542-f7l4ty2j 458 60 RNA RNA NNP cord-002542-f7l4ty2j 458 61 recombination recombination NN cord-002542-f7l4ty2j 458 62 in in IN cord-002542-f7l4ty2j 458 63 the the DT cord-002542-f7l4ty2j 458 64 encapsidated encapsidated JJ cord-002542-f7l4ty2j 458 65 genome genome NN cord-002542-f7l4ty2j 458 66 of of IN cord-002542-f7l4ty2j 458 67 a a DT cord-002542-f7l4ty2j 458 68 eukaryotic eukaryotic JJ cord-002542-f7l4ty2j 458 69 RNA RNA NNP cord-002542-f7l4ty2j 458 70 virus virus NN cord-002542-f7l4ty2j 458 71 by by IN cord-002542-f7l4ty2j 458 72 next next JJ cord-002542-f7l4ty2j 458 73 - - HYPH cord-002542-f7l4ty2j 458 74 generation generation NN cord-002542-f7l4ty2j 458 75 sequencing sequencing NN cord-002542-f7l4ty2j 458 76 Defective defective JJ cord-002542-f7l4ty2j 458 77 Interfering Interfering NNP cord-002542-f7l4ty2j 458 78 RNAs rna NNS cord-002542-f7l4ty2j 458 79 : : : cord-002542-f7l4ty2j 458 80 Foes foe NNS cord-002542-f7l4ty2j 458 81 of of IN cord-002542-f7l4ty2j 458 82 Viruses virus NNS cord-002542-f7l4ty2j 458 83 and and CC cord-002542-f7l4ty2j 458 84 Friends friend NNS cord-002542-f7l4ty2j 458 85 of of IN cord-002542-f7l4ty2j 458 86 Virologists Virologists NNP cord-002542-f7l4ty2j 458 87 Defective defective JJ cord-002542-f7l4ty2j 458 88 viral viral JJ cord-002542-f7l4ty2j 458 89 particles particle NNS cord-002542-f7l4ty2j 458 90 and and CC cord-002542-f7l4ty2j 458 91 viral viral JJ cord-002542-f7l4ty2j 458 92 disease disease NN cord-002542-f7l4ty2j 458 93 processes process NNS cord-002542-f7l4ty2j 459 1 A a DT cord-002542-f7l4ty2j 459 2 Defective defective JJ cord-002542-f7l4ty2j 460 1 Interfering interfere VBG cord-002542-f7l4ty2j 460 2 Influenza Influenza NNP cord-002542-f7l4ty2j 460 3 RNA RNA NNP cord-002542-f7l4ty2j 460 4 Inhibits inhibit VBZ cord-002542-f7l4ty2j 460 5 Infectious Infectious NNP cord-002542-f7l4ty2j 460 6 Influenza Influenza NNP cord-002542-f7l4ty2j 460 7 Virus Virus NNP cord-002542-f7l4ty2j 460 8 Replication Replication NNP cord-002542-f7l4ty2j 460 9 in in IN cord-002542-f7l4ty2j 460 10 Human Human NNP cord-002542-f7l4ty2j 460 11 Respiratory respiratory JJ cord-002542-f7l4ty2j 460 12 Tract Tract NNP cord-002542-f7l4ty2j 460 13 Cells cell NNS cord-002542-f7l4ty2j 460 14 : : : cord-002542-f7l4ty2j 461 1 A a DT cord-002542-f7l4ty2j 461 2 Potential potential JJ cord-002542-f7l4ty2j 461 3 New New NNP cord-002542-f7l4ty2j 461 4 Human Human NNP cord-002542-f7l4ty2j 461 5 Antiviral Antiviral NNP cord-002542-f7l4ty2j 461 6 Immunostimulatory Immunostimulatory NNP cord-002542-f7l4ty2j 461 7 Defective defective JJ cord-002542-f7l4ty2j 461 8 Viral Viral NNP cord-002542-f7l4ty2j 461 9 Genomes Genomes NNPS cord-002542-f7l4ty2j 461 10 from from IN cord-002542-f7l4ty2j 461 11 Respiratory respiratory JJ cord-002542-f7l4ty2j 461 12 Syncytial Syncytial NNP cord-002542-f7l4ty2j 461 13 Virus virus NN cord-002542-f7l4ty2j 461 14 Promote promote VB cord-002542-f7l4ty2j 461 15 a a DT cord-002542-f7l4ty2j 461 16 Strong strong JJ cord-002542-f7l4ty2j 461 17 Innate Innate NNP cord-002542-f7l4ty2j 461 18 Antiviral Antiviral NNP cord-002542-f7l4ty2j 461 19 Response response NN cord-002542-f7l4ty2j 461 20 during during IN cord-002542-f7l4ty2j 461 21 Infection Infection NNP cord-002542-f7l4ty2j 461 22 in in IN cord-002542-f7l4ty2j 461 23 Mice Mice NNP cord-002542-f7l4ty2j 461 24 and and CC cord-002542-f7l4ty2j 461 25 Humans Humans NNPS cord-002542-f7l4ty2j 461 26 Effects effect NNS cord-002542-f7l4ty2j 461 27 of of IN cord-002542-f7l4ty2j 461 28 defective defective JJ cord-002542-f7l4ty2j 461 29 interfering interfere VBG cord-002542-f7l4ty2j 461 30 viruses virus NNS cord-002542-f7l4ty2j 461 31 on on IN cord-002542-f7l4ty2j 461 32 virus virus NN cord-002542-f7l4ty2j 461 33 replication replication NN cord-002542-f7l4ty2j 461 34 and and CC cord-002542-f7l4ty2j 461 35 pathogenesis pathogenesis NN cord-002542-f7l4ty2j 461 36 in in IN cord-002542-f7l4ty2j 461 37 vitro vitro FW cord-002542-f7l4ty2j 461 38 and and CC cord-002542-f7l4ty2j 461 39 in in IN cord-002542-f7l4ty2j 461 40 vivo vivo NN cord-002542-f7l4ty2j 461 41 Defective defective JJ cord-002542-f7l4ty2j 461 42 viral viral JJ cord-002542-f7l4ty2j 461 43 genomes genome NNS cord-002542-f7l4ty2j 461 44 arising arise VBG cord-002542-f7l4ty2j 461 45 in in IN cord-002542-f7l4ty2j 461 46 vivo vivo NN cord-002542-f7l4ty2j 461 47 provide provide VBP cord-002542-f7l4ty2j 461 48 critical critical JJ cord-002542-f7l4ty2j 461 49 danger danger NN cord-002542-f7l4ty2j 461 50 signals signal NNS cord-002542-f7l4ty2j 461 51 for for IN cord-002542-f7l4ty2j 461 52 the the DT cord-002542-f7l4ty2j 461 53 triggering triggering NN cord-002542-f7l4ty2j 461 54 of of IN cord-002542-f7l4ty2j 461 55 lung lung NN cord-002542-f7l4ty2j 461 56 antiviral antiviral JJ cord-002542-f7l4ty2j 461 57 immunity immunity NN cord-002542-f7l4ty2j 461 58 Engineering Engineering NNP cord-002542-f7l4ty2j 461 59 of of IN cord-002542-f7l4ty2j 461 60 homologous homologous JJ cord-002542-f7l4ty2j 461 61 recombination recombination NN cord-002542-f7l4ty2j 461 62 hotspots hotspot NNS cord-002542-f7l4ty2j 461 63 with with IN cord-002542-f7l4ty2j 461 64 AU AU NNP cord-002542-f7l4ty2j 461 65 - - HYPH cord-002542-f7l4ty2j 461 66 rich rich JJ cord-002542-f7l4ty2j 461 67 sequences sequence NNS cord-002542-f7l4ty2j 461 68 in in IN cord-002542-f7l4ty2j 461 69 brome brome NNP cord-002542-f7l4ty2j 461 70 mosaic mosaic NNP cord-002542-f7l4ty2j 461 71 virus virus NN cord-002542-f7l4ty2j 461 72 Identification identification NN cord-002542-f7l4ty2j 461 73 and and CC cord-002542-f7l4ty2j 461 74 manipulation manipulation NN cord-002542-f7l4ty2j 461 75 of of IN cord-002542-f7l4ty2j 461 76 the the DT cord-002542-f7l4ty2j 461 77 molecular molecular JJ cord-002542-f7l4ty2j 461 78 determinants determinant NNS cord-002542-f7l4ty2j 461 79 influencing influence VBG cord-002542-f7l4ty2j 461 80 poliovirus poliovirus NN cord-002542-f7l4ty2j 461 81 recombination recombination NN cord-002542-f7l4ty2j 461 82 Defective defective JJ cord-002542-f7l4ty2j 461 83 interfering interfere VBG cord-002542-f7l4ty2j 461 84 influenza influenza NN cord-002542-f7l4ty2j 461 85 virus virus NN cord-002542-f7l4ty2j 461 86 RNAs rna NNS cord-002542-f7l4ty2j 461 87 : : : cord-002542-f7l4ty2j 461 88 time time NN cord-002542-f7l4ty2j 461 89 to to TO cord-002542-f7l4ty2j 461 90 reevaluate reevaluate VB cord-002542-f7l4ty2j 461 91 their -PRON- PRP$ cord-002542-f7l4ty2j 461 92 clinical clinical JJ cord-002542-f7l4ty2j 461 93 potential potential NN cord-002542-f7l4ty2j 461 94 as as IN cord-002542-f7l4ty2j 461 95 broad broad JJ cord-002542-f7l4ty2j 461 96 - - HYPH cord-002542-f7l4ty2j 461 97 spectrum spectrum NN cord-002542-f7l4ty2j 461 98 antivirals antiviral NNS cord-002542-f7l4ty2j 461 99 ? ? . cord-002542-f7l4ty2j 462 1 Analysis analysis NN cord-002542-f7l4ty2j 462 2 of of IN cord-002542-f7l4ty2j 462 3 efficiently efficiently RB cord-002542-f7l4ty2j 462 4 packaged package VBN cord-002542-f7l4ty2j 462 5 defective defective JJ cord-002542-f7l4ty2j 462 6 interfering interfere VBG cord-002542-f7l4ty2j 462 7 RNAs rna NNS cord-002542-f7l4ty2j 462 8 of of IN cord-002542-f7l4ty2j 462 9 murine murine JJ cord-002542-f7l4ty2j 462 10 coronavirus coronavirus NN cord-002542-f7l4ty2j 462 11 : : : cord-002542-f7l4ty2j 462 12 localization localization NN cord-002542-f7l4ty2j 462 13 of of IN cord-002542-f7l4ty2j 462 14 a a DT cord-002542-f7l4ty2j 462 15 possible possible JJ cord-002542-f7l4ty2j 462 16 RNA rna NN cord-002542-f7l4ty2j 462 17 - - HYPH cord-002542-f7l4ty2j 462 18 packaging packaging NN cord-002542-f7l4ty2j 462 19 signal signal NN cord-002542-f7l4ty2j 462 20 Defective defective JJ cord-002542-f7l4ty2j 462 21 virus virus NN cord-002542-f7l4ty2j 462 22 drives drive VBZ cord-002542-f7l4ty2j 462 23 human human JJ cord-002542-f7l4ty2j 462 24 immunodeficiency immunodeficiency NN cord-002542-f7l4ty2j 462 25 virus virus NN cord-002542-f7l4ty2j 462 26 infection infection NN cord-002542-f7l4ty2j 462 27 , , , cord-002542-f7l4ty2j 462 28 persistence persistence NN cord-002542-f7l4ty2j 462 29 , , , cord-002542-f7l4ty2j 462 30 and and CC cord-002542-f7l4ty2j 462 31 pathogenesis pathogenesis NN cord-002542-f7l4ty2j 462 32 Biased bias VBN cord-002542-f7l4ty2j 462 33 hypermutation hypermutation NN cord-002542-f7l4ty2j 462 34 and and CC cord-002542-f7l4ty2j 462 35 other other JJ cord-002542-f7l4ty2j 462 36 genetic genetic JJ cord-002542-f7l4ty2j 462 37 changes change NNS cord-002542-f7l4ty2j 462 38 in in IN cord-002542-f7l4ty2j 462 39 defective defective JJ cord-002542-f7l4ty2j 462 40 measles measle NNS cord-002542-f7l4ty2j 462 41 viruses virus NNS cord-002542-f7l4ty2j 462 42 in in IN cord-002542-f7l4ty2j 462 43 human human JJ cord-002542-f7l4ty2j 462 44 brain brain NN cord-002542-f7l4ty2j 462 45 infections infection NNS cord-002542-f7l4ty2j 462 46 Defective defective JJ cord-002542-f7l4ty2j 462 47 interfering interfere VBG cord-002542-f7l4ty2j 462 48 viral viral JJ cord-002542-f7l4ty2j 462 49 particles particle NNS cord-002542-f7l4ty2j 462 50 in in IN cord-002542-f7l4ty2j 462 51 acute acute JJ cord-002542-f7l4ty2j 462 52 dengue dengue NN cord-002542-f7l4ty2j 462 53 infections infection NNS cord-002542-f7l4ty2j 462 54 Genetic genetic JJ cord-002542-f7l4ty2j 462 55 analysis analysis NN cord-002542-f7l4ty2j 462 56 of of IN cord-002542-f7l4ty2j 462 57 hepatitis hepatitis NN cord-002542-f7l4ty2j 462 58 C C NNP cord-002542-f7l4ty2j 462 59 virus virus NN cord-002542-f7l4ty2j 462 60 with with IN cord-002542-f7l4ty2j 462 61 defective defective JJ cord-002542-f7l4ty2j 462 62 genome genome NN cord-002542-f7l4ty2j 462 63 and and CC cord-002542-f7l4ty2j 462 64 its -PRON- PRP$ cord-002542-f7l4ty2j 462 65 infectivity infectivity NN cord-002542-f7l4ty2j 462 66 in in IN cord-002542-f7l4ty2j 462 67 vitro vitro FW cord-002542-f7l4ty2j 462 68 Internally internally RB cord-002542-f7l4ty2j 462 69 deleted delete VBN cord-002542-f7l4ty2j 462 70 WNV WNV NNP cord-002542-f7l4ty2j 462 71 genomes genome NNS cord-002542-f7l4ty2j 462 72 isolated isolate VBN cord-002542-f7l4ty2j 462 73 from from IN cord-002542-f7l4ty2j 462 74 exotic exotic JJ cord-002542-f7l4ty2j 462 75 birds bird NNS cord-002542-f7l4ty2j 462 76 in in IN cord-002542-f7l4ty2j 462 77 New New NNP cord-002542-f7l4ty2j 462 78 Mexico Mexico NNP cord-002542-f7l4ty2j 462 79 : : : cord-002542-f7l4ty2j 462 80 function function NN cord-002542-f7l4ty2j 462 81 in in IN cord-002542-f7l4ty2j 462 82 cells cell NNS cord-002542-f7l4ty2j 462 83 , , , cord-002542-f7l4ty2j 462 84 mosquitoes mosquito NNS cord-002542-f7l4ty2j 462 85 , , , cord-002542-f7l4ty2j 462 86 and and CC cord-002542-f7l4ty2j 462 87 mice mouse NNS cord-002542-f7l4ty2j 462 88 Sequence sequence NN cord-002542-f7l4ty2j 462 89 analysis analysis NN cord-002542-f7l4ty2j 462 90 of of IN cord-002542-f7l4ty2j 462 91 in in IN cord-002542-f7l4ty2j 462 92 vivo vivo NN cord-002542-f7l4ty2j 462 93 defective defective JJ cord-002542-f7l4ty2j 462 94 interfering interfere VBG cord-002542-f7l4ty2j 462 95 - - HYPH cord-002542-f7l4ty2j 462 96 like like JJ cord-002542-f7l4ty2j 462 97 RNA RNA NNP cord-002542-f7l4ty2j 462 98 of of IN cord-002542-f7l4ty2j 462 99 influenza influenza NN cord-002542-f7l4ty2j 462 100 A a DT cord-002542-f7l4ty2j 462 101 H1N1 H1N1 NNP cord-002542-f7l4ty2j 462 102 pandemic pandemic NN cord-002542-f7l4ty2j 462 103 virus virus NN cord-002542-f7l4ty2j 462 104 Flock Flock NNP cord-002542-f7l4ty2j 462 105 House House NNP cord-002542-f7l4ty2j 462 106 virus virus NN cord-002542-f7l4ty2j 462 107 : : : cord-002542-f7l4ty2j 462 108 a a DT cord-002542-f7l4ty2j 462 109 nodavirus nodavirus NN cord-002542-f7l4ty2j 462 110 isolated isolate VBN cord-002542-f7l4ty2j 462 111 from from IN cord-002542-f7l4ty2j 462 112 Costelytra Costelytra NNP cord-002542-f7l4ty2j 462 113 zealandica zealandica NNP cord-002542-f7l4ty2j 463 1 ( ( -LRB- cord-002542-f7l4ty2j 463 2 White White NNP cord-002542-f7l4ty2j 463 3 ) ) -RRB- cord-002542-f7l4ty2j 464 1 ( ( -LRB- cord-002542-f7l4ty2j 464 2 Coleoptera Coleoptera NNP cord-002542-f7l4ty2j 464 3 : : : cord-002542-f7l4ty2j 464 4 Scarabaeidae scarabaeidae NN cord-002542-f7l4ty2j 464 5 ) ) -RRB- cord-002542-f7l4ty2j 464 6 Replication replication NN cord-002542-f7l4ty2j 464 7 of of IN cord-002542-f7l4ty2j 464 8 flock flock NN cord-002542-f7l4ty2j 464 9 house house NN cord-002542-f7l4ty2j 464 10 virus virus NN cord-002542-f7l4ty2j 464 11 in in IN cord-002542-f7l4ty2j 464 12 three three CD cord-002542-f7l4ty2j 464 13 genera genus NNS cord-002542-f7l4ty2j 464 14 of of IN cord-002542-f7l4ty2j 464 15 medically medically RB cord-002542-f7l4ty2j 464 16 important important JJ cord-002542-f7l4ty2j 464 17 insects insect NNS cord-002542-f7l4ty2j 464 18 Flock Flock NNP cord-002542-f7l4ty2j 464 19 house house NN cord-002542-f7l4ty2j 464 20 virus virus NN cord-002542-f7l4ty2j 464 21 : : : cord-002542-f7l4ty2j 464 22 a a DT cord-002542-f7l4ty2j 464 23 model model NN cord-002542-f7l4ty2j 464 24 system system NN cord-002542-f7l4ty2j 464 25 for for IN cord-002542-f7l4ty2j 464 26 understanding understand VBG cord-002542-f7l4ty2j 464 27 non non JJ cord-002542-f7l4ty2j 464 28 - - JJ cord-002542-f7l4ty2j 464 29 enveloped enveloped JJ cord-002542-f7l4ty2j 464 30 virus virus NN cord-002542-f7l4ty2j 464 31 entry entry NN cord-002542-f7l4ty2j 464 32 and and CC cord-002542-f7l4ty2j 464 33 membrane membrane NN cord-002542-f7l4ty2j 464 34 penetration penetration NN cord-002542-f7l4ty2j 465 1 Induction induction NN cord-002542-f7l4ty2j 465 2 and and CC cord-002542-f7l4ty2j 465 3 suppression suppression NN cord-002542-f7l4ty2j 465 4 of of IN cord-002542-f7l4ty2j 465 5 RNA RNA NNP cord-002542-f7l4ty2j 465 6 silencing silencing NN cord-002542-f7l4ty2j 465 7 by by IN cord-002542-f7l4ty2j 465 8 an an DT cord-002542-f7l4ty2j 465 9 animal animal NN cord-002542-f7l4ty2j 465 10 virus virus NN cord-002542-f7l4ty2j 465 11 Evidence evidence NN cord-002542-f7l4ty2j 465 12 that that IN cord-002542-f7l4ty2j 465 13 the the DT cord-002542-f7l4ty2j 465 14 packaging packaging NN cord-002542-f7l4ty2j 465 15 signal signal NN cord-002542-f7l4ty2j 465 16 for for IN cord-002542-f7l4ty2j 465 17 nodaviral nodaviral NNP cord-002542-f7l4ty2j 465 18 RNA2 RNA2 NNP cord-002542-f7l4ty2j 465 19 is be VBZ cord-002542-f7l4ty2j 465 20 a a DT cord-002542-f7l4ty2j 465 21 bulged bulge VBN cord-002542-f7l4ty2j 465 22 stem stem NN cord-002542-f7l4ty2j 465 23 - - HYPH cord-002542-f7l4ty2j 465 24 loop loop NN cord-002542-f7l4ty2j 465 25 cis cis NNP cord-002542-f7l4ty2j 465 26 - - HYPH cord-002542-f7l4ty2j 465 27 acting act VBG cord-002542-f7l4ty2j 465 28 requirements requirement NNS cord-002542-f7l4ty2j 465 29 for for IN cord-002542-f7l4ty2j 465 30 the the DT cord-002542-f7l4ty2j 465 31 replication replication NN cord-002542-f7l4ty2j 465 32 of of IN cord-002542-f7l4ty2j 465 33 flock flock NN cord-002542-f7l4ty2j 465 34 house house NN cord-002542-f7l4ty2j 465 35 virus virus NN cord-002542-f7l4ty2j 465 36 RNA RNA NNP cord-002542-f7l4ty2j 465 37 2 2 CD cord-002542-f7l4ty2j 465 38 Molecular molecular JJ cord-002542-f7l4ty2j 465 39 characterization characterization NN cord-002542-f7l4ty2j 465 40 of of IN cord-002542-f7l4ty2j 465 41 Drosophila drosophila JJ cord-002542-f7l4ty2j 465 42 cells cell NNS cord-002542-f7l4ty2j 465 43 persistently persistently RB cord-002542-f7l4ty2j 465 44 infected infect VBN cord-002542-f7l4ty2j 465 45 with with IN cord-002542-f7l4ty2j 465 46 Flock Flock NNP cord-002542-f7l4ty2j 465 47 House House NNP cord-002542-f7l4ty2j 465 48 virus virus NN cord-002542-f7l4ty2j 465 49 Discovery Discovery NNP cord-002542-f7l4ty2j 465 50 of of IN cord-002542-f7l4ty2j 465 51 functional functional JJ cord-002542-f7l4ty2j 465 52 genomic genomic JJ cord-002542-f7l4ty2j 465 53 motifs motif NNS cord-002542-f7l4ty2j 465 54 in in IN cord-002542-f7l4ty2j 465 55 viruses virus NNS cord-002542-f7l4ty2j 465 56 with with IN cord-002542-f7l4ty2j 465 57 ViReMa virema FW cord-002542-f7l4ty2j 465 58 - - HYPH cord-002542-f7l4ty2j 465 59 a a DT cord-002542-f7l4ty2j 465 60 Virus Virus NNP cord-002542-f7l4ty2j 465 61 Recombination Recombination NNP cord-002542-f7l4ty2j 465 62 Mapper mapper NN cord-002542-f7l4ty2j 465 63 - - HYPH cord-002542-f7l4ty2j 465 64 for for IN cord-002542-f7l4ty2j 465 65 analysis analysis NN cord-002542-f7l4ty2j 465 66 of of IN cord-002542-f7l4ty2j 465 67 next next JJ cord-002542-f7l4ty2j 465 68 - - HYPH cord-002542-f7l4ty2j 465 69 generation generation NN cord-002542-f7l4ty2j 465 70 sequencing sequencing NN cord-002542-f7l4ty2j 465 71 data datum NNS cord-002542-f7l4ty2j 465 72 RNA RNA NNP cord-002542-f7l4ty2j 465 73 - - HYPH cord-002542-f7l4ty2j 465 74 mediated mediate VBN cord-002542-f7l4ty2j 465 75 interference interference NN cord-002542-f7l4ty2j 465 76 and and CC cord-002542-f7l4ty2j 465 77 reverse reverse VB cord-002542-f7l4ty2j 465 78 transcription transcription NN cord-002542-f7l4ty2j 465 79 control control NN cord-002542-f7l4ty2j 465 80 the the DT cord-002542-f7l4ty2j 465 81 persistence persistence NN cord-002542-f7l4ty2j 465 82 of of IN cord-002542-f7l4ty2j 465 83 RNA RNA NNP cord-002542-f7l4ty2j 465 84 viruses virus NNS cord-002542-f7l4ty2j 465 85 in in IN cord-002542-f7l4ty2j 465 86 the the DT cord-002542-f7l4ty2j 465 87 insect insect NN cord-002542-f7l4ty2j 465 88 model model NN cord-002542-f7l4ty2j 465 89 Drosophila Drosophila NNP cord-002542-f7l4ty2j 465 90 Host Host NNP cord-002542-f7l4ty2j 465 91 RNAs rna NNS cord-002542-f7l4ty2j 465 92 , , , cord-002542-f7l4ty2j 465 93 including include VBG cord-002542-f7l4ty2j 465 94 transposons transposon NNS cord-002542-f7l4ty2j 465 95 , , , cord-002542-f7l4ty2j 466 1 are be VBP cord-002542-f7l4ty2j 466 2 encapsidated encapsidate VBN cord-002542-f7l4ty2j 466 3 by by IN cord-002542-f7l4ty2j 466 4 a a DT cord-002542-f7l4ty2j 466 5 eukaryotic eukaryotic JJ cord-002542-f7l4ty2j 466 6 single single RB cord-002542-f7l4ty2j 466 7 - - HYPH cord-002542-f7l4ty2j 466 8 stranded strand VBN cord-002542-f7l4ty2j 466 9 RNA RNA NNP cord-002542-f7l4ty2j 466 10 virus virus NN cord-002542-f7l4ty2j 466 11 ClickSeq ClickSeq NNP cord-002542-f7l4ty2j 466 12 : : : cord-002542-f7l4ty2j 467 1 Fragmentation fragmentation NN cord-002542-f7l4ty2j 467 2 - - HYPH cord-002542-f7l4ty2j 467 3 Free Free NNP cord-002542-f7l4ty2j 467 4 Next Next NNP cord-002542-f7l4ty2j 467 5 - - HYPH cord-002542-f7l4ty2j 467 6 Generation Generation NNP cord-002542-f7l4ty2j 467 7 Sequencing Sequencing NNP cord-002542-f7l4ty2j 467 8 via via IN cord-002542-f7l4ty2j 467 9 Click Click NNP cord-002542-f7l4ty2j 467 10 Ligation Ligation NNP cord-002542-f7l4ty2j 467 11 of of IN cord-002542-f7l4ty2j 467 12 Adaptors adaptor NNS cord-002542-f7l4ty2j 468 1 to to IN cord-002542-f7l4ty2j 468 2 Stochastically Stochastically NNP cord-002542-f7l4ty2j 468 3 Terminated terminate VBN cord-002542-f7l4ty2j 468 4 3'-Azido 3'-Azido NNP cord-002542-f7l4ty2j 469 1 cDNAs cDNAs . cord-002542-f7l4ty2j 470 1 Solid solid JJ cord-002542-f7l4ty2j 470 2 phase phase NN cord-002542-f7l4ty2j 470 3 click click VBP cord-002542-f7l4ty2j 470 4 ligation ligation NN cord-002542-f7l4ty2j 470 5 for for IN cord-002542-f7l4ty2j 470 6 the the DT cord-002542-f7l4ty2j 470 7 synthesis synthesis NN cord-002542-f7l4ty2j 470 8 of of IN cord-002542-f7l4ty2j 470 9 very very RB cord-002542-f7l4ty2j 470 10 long long JJ cord-002542-f7l4ty2j 470 11 oligonucleotides oligonucleotide NNS cord-002542-f7l4ty2j 471 1 A a DT cord-002542-f7l4ty2j 471 2 first first JJ cord-002542-f7l4ty2j 471 3 look look NN cord-002542-f7l4ty2j 471 4 at at IN cord-002542-f7l4ty2j 471 5 the the DT cord-002542-f7l4ty2j 471 6 Oxford Oxford NNP cord-002542-f7l4ty2j 471 7 Nanopore Nanopore NNP cord-002542-f7l4ty2j 471 8 MinION minion NN cord-002542-f7l4ty2j 471 9 sequencer sequencer NN cord-002542-f7l4ty2j 471 10 Nanopore Nanopore NNP cord-002542-f7l4ty2j 471 11 sequencing sequencing NN cord-002542-f7l4ty2j 471 12 and and CC cord-002542-f7l4ty2j 471 13 assembly assembly NN cord-002542-f7l4ty2j 471 14 of of IN cord-002542-f7l4ty2j 471 15 a a DT cord-002542-f7l4ty2j 471 16 human human JJ cord-002542-f7l4ty2j 471 17 genome genome NN cord-002542-f7l4ty2j 471 18 with with IN cord-002542-f7l4ty2j 471 19 ultra ultra JJ cord-002542-f7l4ty2j 471 20 - - JJ cord-002542-f7l4ty2j 471 21 long long JJ cord-002542-f7l4ty2j 471 22 reads read VBZ cord-002542-f7l4ty2j 471 23 Rapid Rapid NNP cord-002542-f7l4ty2j 471 24 metagenomic metagenomic JJ cord-002542-f7l4ty2j 471 25 identification identification NN cord-002542-f7l4ty2j 471 26 of of IN cord-002542-f7l4ty2j 471 27 viral viral JJ cord-002542-f7l4ty2j 471 28 pathogens pathogen NNS cord-002542-f7l4ty2j 471 29 in in IN cord-002542-f7l4ty2j 471 30 clinical clinical JJ cord-002542-f7l4ty2j 471 31 samples sample NNS cord-002542-f7l4ty2j 471 32 by by IN cord-002542-f7l4ty2j 471 33 real real JJ cord-002542-f7l4ty2j 471 34 - - HYPH cord-002542-f7l4ty2j 471 35 time time NN cord-002542-f7l4ty2j 471 36 nanopore nanopore JJ cord-002542-f7l4ty2j 471 37 sequencing sequencing NN cord-002542-f7l4ty2j 471 38 analysis analysis NN cord-002542-f7l4ty2j 471 39 Real real JJ cord-002542-f7l4ty2j 471 40 - - HYPH cord-002542-f7l4ty2j 471 41 time time NN cord-002542-f7l4ty2j 471 42 , , , cord-002542-f7l4ty2j 471 43 portable portable JJ cord-002542-f7l4ty2j 471 44 genome genome NN cord-002542-f7l4ty2j 471 45 sequencing sequencing NN cord-002542-f7l4ty2j 471 46 for for IN cord-002542-f7l4ty2j 471 47 Ebola Ebola NNP cord-002542-f7l4ty2j 471 48 surveillance surveillance NN cord-002542-f7l4ty2j 471 49 MinION minion XX cord-002542-f7l4ty2j 471 50 nanopore nanopore JJ cord-002542-f7l4ty2j 471 51 sequencing sequencing NN cord-002542-f7l4ty2j 471 52 of of IN cord-002542-f7l4ty2j 471 53 an an DT cord-002542-f7l4ty2j 471 54 influenza influenza NN cord-002542-f7l4ty2j 471 55 genome genome NN cord-002542-f7l4ty2j 471 56 Highly highly RB cord-002542-f7l4ty2j 471 57 parallel parallel JJ cord-002542-f7l4ty2j 471 58 direct direct JJ cord-002542-f7l4ty2j 471 59 RNA rna NN cord-002542-f7l4ty2j 471 60 sequencing sequencing NN cord-002542-f7l4ty2j 471 61 on on IN cord-002542-f7l4ty2j 471 62 an an DT cord-002542-f7l4ty2j 471 63 array array NN cord-002542-f7l4ty2j 471 64 of of IN cord-002542-f7l4ty2j 471 65 nanopores nanopore NNS cord-002542-f7l4ty2j 471 66 . . . cord-002542-f7l4ty2j 472 1 bioRxiv biorxiv RB cord-002542-f7l4ty2j 473 1 Improved improved JJ cord-002542-f7l4ty2j 473 2 data data NN cord-002542-f7l4ty2j 473 3 analysis analysis NN cord-002542-f7l4ty2j 473 4 for for IN cord-002542-f7l4ty2j 473 5 the the DT cord-002542-f7l4ty2j 473 6 MinION MinION NNP cord-002542-f7l4ty2j 473 7 nanopore nanopore NNP cord-002542-f7l4ty2j 473 8 sequencer sequencer NN cord-002542-f7l4ty2j 474 1 CoVaMa covama NN cord-002542-f7l4ty2j 474 2 : : : cord-002542-f7l4ty2j 474 3 Co co NN cord-002542-f7l4ty2j 474 4 - - NN cord-002542-f7l4ty2j 474 5 Variation Variation NNP cord-002542-f7l4ty2j 474 6 Mapper mapper NN cord-002542-f7l4ty2j 474 7 for for IN cord-002542-f7l4ty2j 474 8 disequilibrium disequilibrium NN cord-002542-f7l4ty2j 474 9 analysis analysis NN cord-002542-f7l4ty2j 474 10 of of IN cord-002542-f7l4ty2j 474 11 mutant mutant JJ cord-002542-f7l4ty2j 474 12 loci locus NNS cord-002542-f7l4ty2j 474 13 in in IN cord-002542-f7l4ty2j 474 14 viral viral JJ cord-002542-f7l4ty2j 474 15 populations population NNS cord-002542-f7l4ty2j 474 16 using use VBG cord-002542-f7l4ty2j 474 17 next next JJ cord-002542-f7l4ty2j 474 18 - - HYPH cord-002542-f7l4ty2j 474 19 generation generation NN cord-002542-f7l4ty2j 474 20 sequence sequence NN cord-002542-f7l4ty2j 474 21 data data NN cord-002542-f7l4ty2j 474 22 Poly(A)-ClickSeq Poly(A)-ClickSeq NNP cord-002542-f7l4ty2j 474 23 : : : cord-002542-f7l4ty2j 474 24 click click VB cord-002542-f7l4ty2j 474 25 - - HYPH cord-002542-f7l4ty2j 474 26 chemistry chemistry NN cord-002542-f7l4ty2j 474 27 for for IN cord-002542-f7l4ty2j 474 28 next next JJ cord-002542-f7l4ty2j 474 29 - - HYPH cord-002542-f7l4ty2j 474 30 generation generation NN cord-002542-f7l4ty2j 474 31 3 3 CD cord-002542-f7l4ty2j 474 32 0 0 CD cord-002542-f7l4ty2j 475 1 -end -end : cord-002542-f7l4ty2j 475 2 sequencing sequence VBG cord-002542-f7l4ty2j 475 3 without without IN cord-002542-f7l4ty2j 475 4 RNA RNA NNP cord-002542-f7l4ty2j 475 5 enrichment enrichment NN cord-002542-f7l4ty2j 475 6 or or CC cord-002542-f7l4ty2j 475 7 fragmentation fragmentation NN cord-002542-f7l4ty2j 476 1 Cutadapt Cutadapt NNP cord-002542-f7l4ty2j 476 2 removes remove VBZ cord-002542-f7l4ty2j 476 3 adapter adapter NN cord-002542-f7l4ty2j 476 4 sequences sequence NNS cord-002542-f7l4ty2j 476 5 from from IN cord-002542-f7l4ty2j 476 6 high high JJ cord-002542-f7l4ty2j 476 7 - - HYPH cord-002542-f7l4ty2j 476 8 throughput throughput NN cord-002542-f7l4ty2j 476 9 sequencing sequencing NN cord-002542-f7l4ty2j 476 10 reads read VBZ cord-002542-f7l4ty2j 476 11 Ultrafast ultrafast NN cord-002542-f7l4ty2j 476 12 and and CC cord-002542-f7l4ty2j 476 13 memory memory NN cord-002542-f7l4ty2j 476 14 - - HYPH cord-002542-f7l4ty2j 476 15 efficient efficient JJ cord-002542-f7l4ty2j 476 16 alignment alignment NN cord-002542-f7l4ty2j 476 17 of of IN cord-002542-f7l4ty2j 476 18 short short JJ cord-002542-f7l4ty2j 476 19 DNA dna NN cord-002542-f7l4ty2j 476 20 sequences sequence NNS cord-002542-f7l4ty2j 476 21 to to IN cord-002542-f7l4ty2j 476 22 the the DT cord-002542-f7l4ty2j 476 23 human human JJ cord-002542-f7l4ty2j 476 24 genome genome NN cord-002542-f7l4ty2j 476 25 Poretools Poretools NNP cord-002542-f7l4ty2j 476 26 : : : cord-002542-f7l4ty2j 476 27 a a DT cord-002542-f7l4ty2j 476 28 toolkit toolkit NN cord-002542-f7l4ty2j 476 29 for for IN cord-002542-f7l4ty2j 476 30 analyzing analyze VBG cord-002542-f7l4ty2j 476 31 nanopore nanopore NNP cord-002542-f7l4ty2j 476 32 sequence sequence NN cord-002542-f7l4ty2j 476 33 data data NNP cord-002542-f7l4ty2j 476 34 Tablet Tablet NNP cord-002542-f7l4ty2j 476 35 - - HYPH cord-002542-f7l4ty2j 476 36 next next JJ cord-002542-f7l4ty2j 476 37 generation generation NN cord-002542-f7l4ty2j 476 38 sequence sequence NN cord-002542-f7l4ty2j 476 39 assembly assembly NN cord-002542-f7l4ty2j 476 40 visualization visualization NN cord-002542-f7l4ty2j 477 1 The the DT cord-002542-f7l4ty2j 477 2 Sequence Sequence NNP cord-002542-f7l4ty2j 477 3 Alignment Alignment NNP cord-002542-f7l4ty2j 477 4 / / SYM cord-002542-f7l4ty2j 477 5 Map Map NNP cord-002542-f7l4ty2j 477 6 format format NN cord-002542-f7l4ty2j 477 7 and and CC cord-002542-f7l4ty2j 477 8 SAMtools samtool NNS cord-002542-f7l4ty2j 477 9 Measuring measure VBG cord-002542-f7l4ty2j 477 10 HCV HCV NNP cord-002542-f7l4ty2j 477 11 infectivity infectivity NN cord-002542-f7l4ty2j 477 12 produced produce VBN cord-002542-f7l4ty2j 477 13 in in IN cord-002542-f7l4ty2j 477 14 cell cell NN cord-002542-f7l4ty2j 477 15 culture culture NN cord-002542-f7l4ty2j 477 16 and and CC cord-002542-f7l4ty2j 477 17 in in IN cord-002542-f7l4ty2j 477 18 vivo vivo NNP cord-002542-f7l4ty2j 477 19 Plaque Plaque NNP cord-002542-f7l4ty2j 477 20 assay assay NN cord-002542-f7l4ty2j 477 21 for for IN cord-002542-f7l4ty2j 477 22 black black JJ cord-002542-f7l4ty2j 477 23 beetle beetle NN cord-002542-f7l4ty2j 477 24 virus virus NN cord-002542-f7l4ty2j 477 25 High high JJ cord-002542-f7l4ty2j 477 26 - - HYPH cord-002542-f7l4ty2j 477 27 fidelity fidelity NN cord-002542-f7l4ty2j 477 28 mass mass NN cord-002542-f7l4ty2j 477 29 analysis analysis NN cord-002542-f7l4ty2j 477 30 unveils unveil VBZ cord-002542-f7l4ty2j 477 31 heterogeneity heterogeneity NN cord-002542-f7l4ty2j 477 32 in in IN cord-002542-f7l4ty2j 477 33 intact intact JJ cord-002542-f7l4ty2j 477 34 ribosomal ribosomal JJ cord-002542-f7l4ty2j 477 35 particles particle NNS cord-002542-f7l4ty2j 477 36 Replication replication NN cord-002542-f7l4ty2j 477 37 of of IN cord-002542-f7l4ty2j 477 38 flock flock NN cord-002542-f7l4ty2j 477 39 house house NN cord-002542-f7l4ty2j 477 40 virus virus NN cord-002542-f7l4ty2j 477 41 RNAs rna NNS cord-002542-f7l4ty2j 477 42 from from IN cord-002542-f7l4ty2j 477 43 primary primary JJ cord-002542-f7l4ty2j 477 44 transcripts transcript NNS cord-002542-f7l4ty2j 477 45 made make VBN cord-002542-f7l4ty2j 477 46 in in IN cord-002542-f7l4ty2j 477 47 cells cell NNS cord-002542-f7l4ty2j 477 48 by by IN cord-002542-f7l4ty2j 477 49 RNA RNA NNP cord-002542-f7l4ty2j 477 50 polymerase polymerase NN cord-002542-f7l4ty2j 477 51 II II NNP cord-002542-f7l4ty2j 477 52 Packaging Packaging NNP cord-002542-f7l4ty2j 477 53 host host NN cord-002542-f7l4ty2j 477 54 RNAs rna NNS cord-002542-f7l4ty2j 477 55 in in IN cord-002542-f7l4ty2j 477 56 small small JJ cord-002542-f7l4ty2j 477 57 RNA RNA NNP cord-002542-f7l4ty2j 477 58 viruses virus NNS cord-002542-f7l4ty2j 477 59 : : : cord-002542-f7l4ty2j 478 1 An an DT cord-002542-f7l4ty2j 478 2 inevitable inevitable JJ cord-002542-f7l4ty2j 478 3 consequence consequence NN cord-002542-f7l4ty2j 478 4 of of IN cord-002542-f7l4ty2j 478 5 an an DT cord-002542-f7l4ty2j 478 6 error error NN cord-002542-f7l4ty2j 478 7 - - HYPH cord-002542-f7l4ty2j 478 8 prone prone JJ cord-002542-f7l4ty2j 478 9 polymerase polymerase NN cord-002542-f7l4ty2j 478 10 ? ? . cord-002542-f7l4ty2j 479 1 Double double JJ cord-002542-f7l4ty2j 479 2 indexing indexing NN cord-002542-f7l4ty2j 479 3 overcomes overcome VBZ cord-002542-f7l4ty2j 479 4 inaccuracies inaccuracy NNS cord-002542-f7l4ty2j 479 5 in in IN cord-002542-f7l4ty2j 479 6 multiplex multiplex JJ cord-002542-f7l4ty2j 479 7 sequencing sequencing NN cord-002542-f7l4ty2j 479 8 on on IN cord-002542-f7l4ty2j 479 9 the the DT cord-002542-f7l4ty2j 479 10 Illumina Illumina NNP cord-002542-f7l4ty2j 479 11 platform platform NN cord-002542-f7l4ty2j 479 12 Common common JJ cord-002542-f7l4ty2j 479 13 contaminants contaminant NNS cord-002542-f7l4ty2j 479 14 in in IN cord-002542-f7l4ty2j 479 15 next next JJ cord-002542-f7l4ty2j 479 16 - - HYPH cord-002542-f7l4ty2j 479 17 generation generation NN cord-002542-f7l4ty2j 479 18 sequencing sequencing NN cord-002542-f7l4ty2j 479 19 that that WDT cord-002542-f7l4ty2j 479 20 hinder hinder VBP cord-002542-f7l4ty2j 479 21 discovery discovery NN cord-002542-f7l4ty2j 479 22 of of IN cord-002542-f7l4ty2j 479 23 low low JJ cord-002542-f7l4ty2j 479 24 - - HYPH cord-002542-f7l4ty2j 479 25 abundance abundance NN cord-002542-f7l4ty2j 479 26 microbes microbe NNS cord-002542-f7l4ty2j 479 27 Generation generation NN cord-002542-f7l4ty2j 479 28 and and CC cord-002542-f7l4ty2j 479 29 selection selection NN cord-002542-f7l4ty2j 479 30 of of IN cord-002542-f7l4ty2j 479 31 coronavirus coronavirus NN cord-002542-f7l4ty2j 479 32 defective defective JJ cord-002542-f7l4ty2j 479 33 interfering interfere VBG cord-002542-f7l4ty2j 479 34 RNA RNA NNP cord-002542-f7l4ty2j 479 35 with with IN cord-002542-f7l4ty2j 479 36 large large JJ cord-002542-f7l4ty2j 479 37 open open JJ cord-002542-f7l4ty2j 479 38 reading reading NN cord-002542-f7l4ty2j 479 39 frame frame NN cord-002542-f7l4ty2j 479 40 by by IN cord-002542-f7l4ty2j 479 41 RNA RNA NNP cord-002542-f7l4ty2j 479 42 recombination recombination NN cord-002542-f7l4ty2j 479 43 and and CC cord-002542-f7l4ty2j 479 44 possible possible JJ cord-002542-f7l4ty2j 479 45 editing edit VBG cord-002542-f7l4ty2j 479 46 Flock Flock NNP cord-002542-f7l4ty2j 479 47 house house NN cord-002542-f7l4ty2j 479 48 virus virus NN cord-002542-f7l4ty2j 479 49 replicates replicate VBZ cord-002542-f7l4ty2j 479 50 and and CC cord-002542-f7l4ty2j 479 51 expresses express VBZ cord-002542-f7l4ty2j 479 52 green green JJ cord-002542-f7l4ty2j 479 53 fluorescent fluorescent JJ cord-002542-f7l4ty2j 479 54 protein protein NN cord-002542-f7l4ty2j 479 55 in in IN cord-002542-f7l4ty2j 479 56 mosquitoes mosquito NNS cord-002542-f7l4ty2j 479 57 Long long JJ cord-002542-f7l4ty2j 479 58 - - HYPH cord-002542-f7l4ty2j 479 59 distance distance NN cord-002542-f7l4ty2j 479 60 base base NN cord-002542-f7l4ty2j 479 61 pairing pair VBG cord-002542-f7l4ty2j 479 62 in in IN cord-002542-f7l4ty2j 480 1 flock flock NNP cord-002542-f7l4ty2j 480 2 house house NNP cord-002542-f7l4ty2j 480 3 virus virus NN cord-002542-f7l4ty2j 480 4 RNA1 RNA1 NNP cord-002542-f7l4ty2j 480 5 regulates regulate VBZ cord-002542-f7l4ty2j 480 6 subgenomic subgenomic NNP cord-002542-f7l4ty2j 480 7 RNA3 RNA3 NNP cord-002542-f7l4ty2j 480 8 synthesis synthesis NN cord-002542-f7l4ty2j 480 9 and and CC cord-002542-f7l4ty2j 480 10 RNA2 RNA2 NNP cord-002542-f7l4ty2j 480 11 replication replication NN cord-002542-f7l4ty2j 480 12 Requirements requirement NNS cord-002542-f7l4ty2j 480 13 for for IN cord-002542-f7l4ty2j 480 14 the the DT cord-002542-f7l4ty2j 480 15 self self NN cord-002542-f7l4ty2j 480 16 - - HYPH cord-002542-f7l4ty2j 480 17 directed direct VBN cord-002542-f7l4ty2j 480 18 replication replication NN cord-002542-f7l4ty2j 480 19 of of IN cord-002542-f7l4ty2j 480 20 flock flock NN cord-002542-f7l4ty2j 480 21 house house NN cord-002542-f7l4ty2j 480 22 virus virus NN cord-002542-f7l4ty2j 481 1 RNA RNA NNP cord-002542-f7l4ty2j 481 2 1 1 CD cord-002542-f7l4ty2j 481 3 Replication Replication NNP cord-002542-f7l4ty2j 481 4 of of IN cord-002542-f7l4ty2j 481 5 the the DT cord-002542-f7l4ty2j 481 6 RNA RNA NNP cord-002542-f7l4ty2j 481 7 segments segment NNS cord-002542-f7l4ty2j 481 8 of of IN cord-002542-f7l4ty2j 481 9 a a DT cord-002542-f7l4ty2j 481 10 bipartite bipartite JJ cord-002542-f7l4ty2j 481 11 viral viral JJ cord-002542-f7l4ty2j 481 12 genome genome NN cord-002542-f7l4ty2j 481 13 is be VBZ cord-002542-f7l4ty2j 481 14 coordinated coordinate VBN cord-002542-f7l4ty2j 481 15 by by IN cord-002542-f7l4ty2j 481 16 a a DT cord-002542-f7l4ty2j 481 17 transactivating transactivate VBG cord-002542-f7l4ty2j 481 18 subgenomic subgenomic NNP cord-002542-f7l4ty2j 481 19 RNA RNA NNP cord-002542-f7l4ty2j 482 1 The the DT cord-002542-f7l4ty2j 482 2 cis cis NNP cord-002542-f7l4ty2j 482 3 - - HYPH cord-002542-f7l4ty2j 482 4 acting act VBG cord-002542-f7l4ty2j 482 5 replication replication NN cord-002542-f7l4ty2j 482 6 signal signal NN cord-002542-f7l4ty2j 482 7 at at IN cord-002542-f7l4ty2j 482 8 the the DT cord-002542-f7l4ty2j 482 9 3 3 CD cord-002542-f7l4ty2j 482 10 ' ' NN cord-002542-f7l4ty2j 482 11 end end NN cord-002542-f7l4ty2j 482 12 of of IN cord-002542-f7l4ty2j 482 13 Flock Flock NNP cord-002542-f7l4ty2j 482 14 House House NNP cord-002542-f7l4ty2j 482 15 virus virus NN cord-002542-f7l4ty2j 482 16 RNA2 RNA2 NNP cord-002542-f7l4ty2j 482 17 is be VBZ cord-002542-f7l4ty2j 482 18 RNA3-dependent RNA3-dependent NNP cord-002542-f7l4ty2j 482 19 A a DT cord-002542-f7l4ty2j 482 20 3 3 CD cord-002542-f7l4ty2j 482 21 ' ' '' cord-002542-f7l4ty2j 482 22 terminal terminal JJ cord-002542-f7l4ty2j 482 23 stem stem NN cord-002542-f7l4ty2j 482 24 - - HYPH cord-002542-f7l4ty2j 482 25 loop loop NN cord-002542-f7l4ty2j 482 26 structure structure NN cord-002542-f7l4ty2j 482 27 in in IN cord-002542-f7l4ty2j 483 1 Nodamura Nodamura NNP cord-002542-f7l4ty2j 483 2 virus virus NN cord-002542-f7l4ty2j 483 3 RNA2 RNA2 NNP cord-002542-f7l4ty2j 483 4 forms form VBZ cord-002542-f7l4ty2j 483 5 an an DT cord-002542-f7l4ty2j 483 6 essential essential JJ cord-002542-f7l4ty2j 483 7 cis cis NN cord-002542-f7l4ty2j 483 8 - - HYPH cord-002542-f7l4ty2j 483 9 acting act VBG cord-002542-f7l4ty2j 483 10 signal signal NN cord-002542-f7l4ty2j 483 11 for for IN cord-002542-f7l4ty2j 483 12 RNA rna NN cord-002542-f7l4ty2j 483 13 replication replication NN cord-002542-f7l4ty2j 483 14 Characterization characterization NN cord-002542-f7l4ty2j 483 15 and and CC cord-002542-f7l4ty2j 483 16 template template NN cord-002542-f7l4ty2j 483 17 properties property NNS cord-002542-f7l4ty2j 483 18 of of IN cord-002542-f7l4ty2j 483 19 RNA RNA NNP cord-002542-f7l4ty2j 483 20 dimers dimer NNS cord-002542-f7l4ty2j 483 21 generated generate VBN cord-002542-f7l4ty2j 483 22 during during IN cord-002542-f7l4ty2j 483 23 flock flock NN cord-002542-f7l4ty2j 483 24 house house NNP cord-002542-f7l4ty2j 483 25 virus virus NN cord-002542-f7l4ty2j 483 26 RNA RNA NNP cord-002542-f7l4ty2j 483 27 replication replication NN cord-002542-f7l4ty2j 484 1 The the DT cord-002542-f7l4ty2j 484 2 Oxford Oxford NNP cord-002542-f7l4ty2j 484 3 Nanopore Nanopore NNP cord-002542-f7l4ty2j 484 4 MinION minion NN cord-002542-f7l4ty2j 484 5 : : : cord-002542-f7l4ty2j 484 6 delivery delivery NN cord-002542-f7l4ty2j 484 7 of of IN cord-002542-f7l4ty2j 484 8 nanopore nanopore NNP cord-002542-f7l4ty2j 484 9 sequencing sequence VBG cord-002542-f7l4ty2j 484 10 to to IN cord-002542-f7l4ty2j 484 11 the the DT cord-002542-f7l4ty2j 484 12 genomics genomic NNS cord-002542-f7l4ty2j 484 13 community community NN cord-002542-f7l4ty2j 484 14 Continuous continuous JJ cord-002542-f7l4ty2j 484 15 influenza influenza NN cord-002542-f7l4ty2j 484 16 virus virus NN cord-002542-f7l4ty2j 484 17 production production NN cord-002542-f7l4ty2j 484 18 in in IN cord-002542-f7l4ty2j 484 19 cell cell NN cord-002542-f7l4ty2j 484 20 culture culture NN cord-002542-f7l4ty2j 484 21 shows show VBZ cord-002542-f7l4ty2j 484 22 a a DT cord-002542-f7l4ty2j 484 23 periodic periodic JJ cord-002542-f7l4ty2j 484 24 accumulation accumulation NN cord-002542-f7l4ty2j 484 25 of of IN cord-002542-f7l4ty2j 484 26 defective defective JJ cord-002542-f7l4ty2j 484 27 interfering interfere VBG cord-002542-f7l4ty2j 484 28 particles particle NNS cord-002542-f7l4ty2j 484 29 Nonhomologous Nonhomologous NNP cord-002542-f7l4ty2j 484 30 RNA RNA NNP cord-002542-f7l4ty2j 484 31 recombination recombination NN cord-002542-f7l4ty2j 484 32 in in IN cord-002542-f7l4ty2j 484 33 tombusviruses tombusviruse NNS cord-002542-f7l4ty2j 484 34 : : : cord-002542-f7l4ty2j 484 35 generation generation NN cord-002542-f7l4ty2j 484 36 and and CC cord-002542-f7l4ty2j 484 37 evolution evolution NN cord-002542-f7l4ty2j 484 38 of of IN cord-002542-f7l4ty2j 484 39 defective defective JJ cord-002542-f7l4ty2j 484 40 interfering interfere VBG cord-002542-f7l4ty2j 484 41 RNAs rna NNS cord-002542-f7l4ty2j 484 42 by by IN cord-002542-f7l4ty2j 484 43 stepwise stepwise JJ cord-002542-f7l4ty2j 484 44 deletions deletion NNS cord-002542-f7l4ty2j 485 1 Massive massive JJ cord-002542-f7l4ty2j 485 2 genomic genomic JJ cord-002542-f7l4ty2j 485 3 rearrangement rearrangement NN cord-002542-f7l4ty2j 485 4 acquired acquire VBN cord-002542-f7l4ty2j 485 5 in in IN cord-002542-f7l4ty2j 485 6 a a DT cord-002542-f7l4ty2j 485 7 single single JJ cord-002542-f7l4ty2j 485 8 catastrophic catastrophic JJ cord-002542-f7l4ty2j 485 9 event event NN cord-002542-f7l4ty2j 485 10 during during IN cord-002542-f7l4ty2j 485 11 cancer cancer NN cord-002542-f7l4ty2j 485 12 development development NN cord-002542-f7l4ty2j 485 13 Role role NN cord-002542-f7l4ty2j 485 14 of of IN cord-002542-f7l4ty2j 485 15 Mitochondrial mitochondrial JJ cord-002542-f7l4ty2j 485 16 Membrane membrane NN cord-002542-f7l4ty2j 485 17 Spherules Spherules NNPS cord-002542-f7l4ty2j 485 18 in in IN cord-002542-f7l4ty2j 485 19 Flock Flock NNP cord-002542-f7l4ty2j 485 20 House House NNP cord-002542-f7l4ty2j 485 21 Virus Virus NNP cord-002542-f7l4ty2j 485 22 Replication replication NN cord-002542-f7l4ty2j 486 1 We -PRON- PRP cord-002542-f7l4ty2j 486 2 thank thank VBP cord-002542-f7l4ty2j 486 3 Thomas Thomas NNP cord-002542-f7l4ty2j 486 4 Wood Wood NNP cord-002542-f7l4ty2j 486 5 , , , cord-002542-f7l4ty2j 486 6 Steve Steve NNP cord-002542-f7l4ty2j 486 7 Widen Widen NNP cord-002542-f7l4ty2j 486 8 and and CC cord-002542-f7l4ty2j 486 9 Jill Jill NNP cord-002542-f7l4ty2j 486 10 Thomson Thomson NNP cord-002542-f7l4ty2j 486 11 from from IN cord-002542-f7l4ty2j 486 12 the the DT cord-002542-f7l4ty2j 486 13 UTMB UTMB NNP cord-002542-f7l4ty2j 486 14 Next Next NNP cord-002542-f7l4ty2j 486 15 - - HYPH cord-002542-f7l4ty2j 486 16 Generation Generation NNP cord-002542-f7l4ty2j 486 17 Sequencing Sequencing NNP cord-002542-f7l4ty2j 486 18 core core NN cord-002542-f7l4ty2j 486 19 and and CC cord-002542-f7l4ty2j 486 20 Gillian Gillian NNP cord-002542-f7l4ty2j 486 21 Lynch Lynch NNP cord-002542-f7l4ty2j 486 22 from from IN cord-002542-f7l4ty2j 486 23 the the DT cord-002542-f7l4ty2j 486 24 SCSB SCSB NNP cord-002542-f7l4ty2j 486 25 computing computing NN cord-002542-f7l4ty2j 486 26 facility facility NN cord-002542-f7l4ty2j 486 27 for for IN cord-002542-f7l4ty2j 486 28 support support NN cord-002542-f7l4ty2j 486 29 . . . cord-002542-f7l4ty2j 487 1 We -PRON- PRP cord-002542-f7l4ty2j 487 2 are be VBP cord-002542-f7l4ty2j 487 3 indebted indebted JJ cord-002542-f7l4ty2j 487 4 to to IN cord-002542-f7l4ty2j 487 5 Mariano Mariano NNP cord-002542-f7l4ty2j 487 6 Garcia Garcia NNP cord-002542-f7l4ty2j 487 7 - - HYPH cord-002542-f7l4ty2j 487 8 Blanco Blanco NNP cord-002542-f7l4ty2j 487 9 and and CC cord-002542-f7l4ty2j 487 10 Shelton Shelton NNP cord-002542-f7l4ty2j 487 11 Bradrick Bradrick NNP cord-002542-f7l4ty2j 487 12 and and CC cord-002542-f7l4ty2j 487 13 the the DT cord-002542-f7l4ty2j 487 14 members member NNS cord-002542-f7l4ty2j 487 15 of of IN cord-002542-f7l4ty2j 487 16 their -PRON- PRP$ cord-002542-f7l4ty2j 487 17 lab lab NN cord-002542-f7l4ty2j 487 18 for for IN cord-002542-f7l4ty2j 487 19 sharing share VBG cord-002542-f7l4ty2j 487 20 lab lab NN cord-002542-f7l4ty2j 487 21 space space NN cord-002542-f7l4ty2j 487 22 , , , cord-002542-f7l4ty2j 487 23 helpful helpful JJ cord-002542-f7l4ty2j 487 24 discussions discussion NNS cord-002542-f7l4ty2j 487 25 and and CC cord-002542-f7l4ty2j 487 26 other other JJ cord-002542-f7l4ty2j 487 27 research research NN cord-002542-f7l4ty2j 487 28 support support NN cord-002542-f7l4ty2j 487 29 . . . cord-002542-f7l4ty2j 488 1 We -PRON- PRP cord-002542-f7l4ty2j 488 2 thank thank VBP cord-002542-f7l4ty2j 488 3 Eric Eric NNP cord-002542-f7l4ty2j 488 4 Wagner Wagner NNP cord-002542-f7l4ty2j 488 5 , , , cord-002542-f7l4ty2j 488 6 Jack Jack NNP cord-002542-f7l4ty2j 488 7 Johnson Johnson NNP cord-002542-f7l4ty2j 488 8 and and CC cord-002542-f7l4ty2j 488 9 Bruce Bruce NNP cord-002542-f7l4ty2j 488 10 Torbett Torbett NNP cord-002542-f7l4ty2j 488 11 for for IN cord-002542-f7l4ty2j 488 12 support support NN cord-002542-f7l4ty2j 488 13 and and CC cord-002542-f7l4ty2j 488 14 advice advice NN cord-002542-f7l4ty2j 488 15 . . . cord-002542-f7l4ty2j 489 1 Visualization visualization NN cord-002542-f7l4ty2j 489 2 : : : cord-002542-f7l4ty2j 489 3 AR AR NNP cord-002542-f7l4ty2j 489 4 EJ EJ NNP cord-002542-f7l4ty2j 489 5 . . . cord-002542-f7l4ty2j 490 1 Writing write VBG cord-002542-f7l4ty2j 490 2 -review -review : cord-002542-f7l4ty2j 490 3 & & CC cord-002542-f7l4ty2j 490 4 editing editing NN cord-002542-f7l4ty2j 490 5 : : : cord-002542-f7l4ty2j 490 6 AR AR NNP cord-002542-f7l4ty2j 490 7 EJ EJ NNP cord-002542-f7l4ty2j 490 8 . . .