id sid tid token lemma pos 10_1101-2021_01_07_425675 1 1 Mass Mass NNP 10_1101-2021_01_07_425675 1 2 spectrometry spectrometry NN 10_1101-2021_01_07_425675 1 3 - - HYPH 10_1101-2021_01_07_425675 1 4 based base VBN 10_1101-2021_01_07_425675 1 5 sequencing sequencing NN 10_1101-2021_01_07_425675 1 6 of of IN 10_1101-2021_01_07_425675 1 7 the the DT 10_1101-2021_01_07_425675 1 8 anti anti JJ 10_1101-2021_01_07_425675 1 9 - - JJ 10_1101-2021_01_07_425675 1 10 FLAG FLAG NNP 10_1101-2021_01_07_425675 1 11 - - HYPH 10_1101-2021_01_07_425675 1 12 M2 M2 NNP 10_1101-2021_01_07_425675 1 13 antibody antibody NN 10_1101-2021_01_07_425675 1 14 using use VBG 10_1101-2021_01_07_425675 1 15 multiple multiple JJ 10_1101-2021_01_07_425675 1 16 proteases protease NNS 10_1101-2021_01_07_425675 1 17 and and CC 10_1101-2021_01_07_425675 1 18 a a DT 10_1101-2021_01_07_425675 1 19 dual dual JJ 10_1101-2021_01_07_425675 1 20 fragmentation fragmentation NN 10_1101-2021_01_07_425675 1 21 scheme scheme NN 10_1101-2021_01_07_425675 1 22 1 1 CD 10_1101-2021_01_07_425675 1 23 Mass Mass NNP 10_1101-2021_01_07_425675 1 24 spectrometry spectrometry NN 10_1101-2021_01_07_425675 1 25 - - HYPH 10_1101-2021_01_07_425675 1 26 based base VBN 10_1101-2021_01_07_425675 1 27 sequencing sequencing NN 10_1101-2021_01_07_425675 1 28 of of IN 10_1101-2021_01_07_425675 1 29 the the DT 10_1101-2021_01_07_425675 1 30 anti anti JJ 10_1101-2021_01_07_425675 1 31 - - JJ 10_1101-2021_01_07_425675 1 32 FLAG FLAG NNP 10_1101-2021_01_07_425675 1 33 - - HYPH 10_1101-2021_01_07_425675 1 34 M2 M2 NNP 10_1101-2021_01_07_425675 1 35 antibody antibody NN 10_1101-2021_01_07_425675 1 36 using use VBG 10_1101-2021_01_07_425675 1 37 multiple multiple JJ 10_1101-2021_01_07_425675 1 38 1 1 CD 10_1101-2021_01_07_425675 1 39 proteases protease NNS 10_1101-2021_01_07_425675 1 40 and and CC 10_1101-2021_01_07_425675 1 41 a a DT 10_1101-2021_01_07_425675 1 42 dual dual JJ 10_1101-2021_01_07_425675 1 43 fragmentation fragmentation NN 10_1101-2021_01_07_425675 1 44 scheme scheme NN 10_1101-2021_01_07_425675 1 45 2 2 CD 10_1101-2021_01_07_425675 1 46 3 3 CD 10_1101-2021_01_07_425675 1 47 Authors author NNS 10_1101-2021_01_07_425675 1 48 : : : 10_1101-2021_01_07_425675 1 49 4 4 CD 10_1101-2021_01_07_425675 1 50 Weiwei Weiwei NNP 10_1101-2021_01_07_425675 1 51 Peng1 peng1 CD 10_1101-2021_01_07_425675 1 52 # # $ 10_1101-2021_01_07_425675 1 53 , , , 10_1101-2021_01_07_425675 1 54 Matti Matti NNP 10_1101-2021_01_07_425675 1 55 F. F. NNP 10_1101-2021_01_07_425675 1 56 Pronker1 Pronker1 NNP 10_1101-2021_01_07_425675 1 57 # # NNP 10_1101-2021_01_07_425675 1 58 , , , 10_1101-2021_01_07_425675 1 59 Joost Joost NNP 10_1101-2021_01_07_425675 1 60 Snijder1 Snijder1 NNP 10_1101-2021_01_07_425675 1 61 * * NFP 10_1101-2021_01_07_425675 1 62 5 5 CD 10_1101-2021_01_07_425675 1 63 6 6 CD 10_1101-2021_01_07_425675 1 64 # # $ 10_1101-2021_01_07_425675 1 65 equal equal JJ 10_1101-2021_01_07_425675 1 66 contribution contribution NN 10_1101-2021_01_07_425675 1 67 7 7 CD 10_1101-2021_01_07_425675 1 68 * * SYM 10_1101-2021_01_07_425675 1 69 corresponding correspond VBG 10_1101-2021_01_07_425675 1 70 author author NN 10_1101-2021_01_07_425675 1 71 : : : 10_1101-2021_01_07_425675 1 72 j.snijder@uu.nl j.snijder@uu.nl NNP 10_1101-2021_01_07_425675 1 73 8 8 CD 10_1101-2021_01_07_425675 1 74 9 9 CD 10_1101-2021_01_07_425675 1 75 Affiliation affiliation NN 10_1101-2021_01_07_425675 1 76 : : : 10_1101-2021_01_07_425675 1 77 10 10 CD 10_1101-2021_01_07_425675 1 78 1 1 CD 10_1101-2021_01_07_425675 1 79 Biomolecular Biomolecular NNP 10_1101-2021_01_07_425675 1 80 Mass Mass NNP 10_1101-2021_01_07_425675 1 81 Spectrometry Spectrometry NNP 10_1101-2021_01_07_425675 1 82 and and CC 10_1101-2021_01_07_425675 1 83 Proteomics Proteomics NNP 10_1101-2021_01_07_425675 1 84 , , , 10_1101-2021_01_07_425675 1 85 Bijvoet Bijvoet NNP 10_1101-2021_01_07_425675 1 86 Center Center NNP 10_1101-2021_01_07_425675 1 87 for for IN 10_1101-2021_01_07_425675 1 88 Biomolecular Biomolecular NNP 10_1101-2021_01_07_425675 1 89 Research Research NNP 10_1101-2021_01_07_425675 1 90 11 11 CD 10_1101-2021_01_07_425675 1 91 and and CC 10_1101-2021_01_07_425675 1 92 Utrecht Utrecht NNP 10_1101-2021_01_07_425675 1 93 Institute Institute NNP 10_1101-2021_01_07_425675 1 94 of of IN 10_1101-2021_01_07_425675 1 95 Pharmaceutical Pharmaceutical NNP 10_1101-2021_01_07_425675 1 96 Sciences Sciences NNPS 10_1101-2021_01_07_425675 1 97 , , , 10_1101-2021_01_07_425675 1 98 Utrecht Utrecht NNP 10_1101-2021_01_07_425675 1 99 University University NNP 10_1101-2021_01_07_425675 1 100 , , , 10_1101-2021_01_07_425675 1 101 Padualaan Padualaan NNP 10_1101-2021_01_07_425675 1 102 8 8 CD 10_1101-2021_01_07_425675 1 103 , , , 10_1101-2021_01_07_425675 1 104 3584 3584 CD 10_1101-2021_01_07_425675 1 105 CH CH NNP 10_1101-2021_01_07_425675 1 106 12 12 CD 10_1101-2021_01_07_425675 1 107 Utrecht Utrecht NNP 10_1101-2021_01_07_425675 1 108 , , , 10_1101-2021_01_07_425675 1 109 The the DT 10_1101-2021_01_07_425675 1 110 Netherlands Netherlands NNP 10_1101-2021_01_07_425675 1 111 13 13 CD 10_1101-2021_01_07_425675 1 112 14 14 CD 10_1101-2021_01_07_425675 1 113 Keywords keyword NNS 10_1101-2021_01_07_425675 1 114 : : : 10_1101-2021_01_07_425675 1 115 15 15 CD 10_1101-2021_01_07_425675 1 116 mass mass NN 10_1101-2021_01_07_425675 1 117 spectrometry spectrometry NN 10_1101-2021_01_07_425675 1 118 , , , 10_1101-2021_01_07_425675 1 119 antibody antibody NN 10_1101-2021_01_07_425675 1 120 , , , 10_1101-2021_01_07_425675 1 121 de de NNP 10_1101-2021_01_07_425675 1 122 novo novo NNP 10_1101-2021_01_07_425675 1 123 sequencing sequencing NNP 10_1101-2021_01_07_425675 1 124 , , , 10_1101-2021_01_07_425675 1 125 EThcD EThcD NNP 10_1101-2021_01_07_425675 1 126 , , , 10_1101-2021_01_07_425675 1 127 stepped step VBD 10_1101-2021_01_07_425675 1 128 HCD HCD NNP 10_1101-2021_01_07_425675 1 129 , , , 10_1101-2021_01_07_425675 1 130 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 1 131 , , , 10_1101-2021_01_07_425675 1 132 FLAG FLAG NNP 10_1101-2021_01_07_425675 1 133 tag tag NN 10_1101-2021_01_07_425675 1 134 , , , 10_1101-2021_01_07_425675 1 135 16 16 CD 10_1101-2021_01_07_425675 1 136 anti anti JJ 10_1101-2021_01_07_425675 1 137 - - JJ 10_1101-2021_01_07_425675 1 138 FLAG FLAG NNP 10_1101-2021_01_07_425675 1 139 - - HYPH 10_1101-2021_01_07_425675 1 140 M2 M2 NNP 10_1101-2021_01_07_425675 1 141 . . . 10_1101-2021_01_07_425675 2 1 17 17 CD 10_1101-2021_01_07_425675 2 2 .CC .CC : 10_1101-2021_01_07_425675 2 3 - - : 10_1101-2021_01_07_425675 2 4 BY by IN 10_1101-2021_01_07_425675 2 5 4.0 4.0 CD 10_1101-2021_01_07_425675 2 6 International International NNP 10_1101-2021_01_07_425675 2 7 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 2 8 under under IN 10_1101-2021_01_07_425675 2 9 a a DT 10_1101-2021_01_07_425675 2 10 ( ( -LRB- 10_1101-2021_01_07_425675 2 11 which which WDT 10_1101-2021_01_07_425675 2 12 was be VBD 10_1101-2021_01_07_425675 2 13 not not RB 10_1101-2021_01_07_425675 2 14 certified certify VBN 10_1101-2021_01_07_425675 2 15 by by IN 10_1101-2021_01_07_425675 2 16 peer peer NN 10_1101-2021_01_07_425675 2 17 review review NN 10_1101-2021_01_07_425675 2 18 ) ) -RRB- 10_1101-2021_01_07_425675 2 19 is be VBZ 10_1101-2021_01_07_425675 2 20 the the DT 10_1101-2021_01_07_425675 2 21 author author NN 10_1101-2021_01_07_425675 2 22 / / SYM 10_1101-2021_01_07_425675 2 23 funder funder NN 10_1101-2021_01_07_425675 2 24 , , , 10_1101-2021_01_07_425675 2 25 who who WP 10_1101-2021_01_07_425675 2 26 has have VBZ 10_1101-2021_01_07_425675 2 27 granted grant VBN 10_1101-2021_01_07_425675 2 28 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 2 29 a a DT 10_1101-2021_01_07_425675 2 30 license license NN 10_1101-2021_01_07_425675 2 31 to to TO 10_1101-2021_01_07_425675 2 32 display display VB 10_1101-2021_01_07_425675 2 33 the the DT 10_1101-2021_01_07_425675 2 34 preprint preprint NN 10_1101-2021_01_07_425675 2 35 in in IN 10_1101-2021_01_07_425675 2 36 perpetuity perpetuity NN 10_1101-2021_01_07_425675 2 37 . . . 10_1101-2021_01_07_425675 3 1 It -PRON- PRP 10_1101-2021_01_07_425675 3 2 is be VBZ 10_1101-2021_01_07_425675 3 3 made make VBN 10_1101-2021_01_07_425675 3 4 The the DT 10_1101-2021_01_07_425675 3 5 copyright copyright NN 10_1101-2021_01_07_425675 3 6 holder holder NN 10_1101-2021_01_07_425675 3 7 for for IN 10_1101-2021_01_07_425675 3 8 this this DT 10_1101-2021_01_07_425675 3 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 3 10 version version NN 10_1101-2021_01_07_425675 3 11 posted post VBD 10_1101-2021_01_07_425675 3 12 January January NNP 10_1101-2021_01_07_425675 3 13 8 8 CD 10_1101-2021_01_07_425675 3 14 , , , 10_1101-2021_01_07_425675 3 15 2021 2021 CD 10_1101-2021_01_07_425675 3 16 . . . 10_1101-2021_01_07_425675 3 17 ; ; : 10_1101-2021_01_07_425675 3 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 3 19 : : : 10_1101-2021_01_07_425675 3 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 3 21 preprint preprint NN 10_1101-2021_01_07_425675 3 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 3 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 3 24 2 2 CD 10_1101-2021_01_07_425675 3 25 Abstract Abstract NNP 10_1101-2021_01_07_425675 3 26 : : : 10_1101-2021_01_07_425675 3 27 18 18 CD 10_1101-2021_01_07_425675 3 28 Antibody antibody NN 10_1101-2021_01_07_425675 3 29 sequence sequence NN 10_1101-2021_01_07_425675 3 30 information information NN 10_1101-2021_01_07_425675 3 31 is be VBZ 10_1101-2021_01_07_425675 3 32 crucial crucial JJ 10_1101-2021_01_07_425675 3 33 to to IN 10_1101-2021_01_07_425675 3 34 understanding understand VBG 10_1101-2021_01_07_425675 3 35 the the DT 10_1101-2021_01_07_425675 3 36 structural structural JJ 10_1101-2021_01_07_425675 3 37 basis basis NN 10_1101-2021_01_07_425675 3 38 for for IN 10_1101-2021_01_07_425675 3 39 antigen antigen NNP 10_1101-2021_01_07_425675 3 40 binding bind VBG 10_1101-2021_01_07_425675 3 41 19 19 CD 10_1101-2021_01_07_425675 3 42 and and CC 10_1101-2021_01_07_425675 3 43 enables enable VBZ 10_1101-2021_01_07_425675 3 44 the the DT 10_1101-2021_01_07_425675 3 45 use use NN 10_1101-2021_01_07_425675 3 46 of of IN 10_1101-2021_01_07_425675 3 47 antibodies antibody NNS 10_1101-2021_01_07_425675 3 48 as as IN 10_1101-2021_01_07_425675 3 49 therapeutics therapeutic NNS 10_1101-2021_01_07_425675 3 50 and and CC 10_1101-2021_01_07_425675 3 51 research research NN 10_1101-2021_01_07_425675 3 52 tools tool NNS 10_1101-2021_01_07_425675 3 53 . . . 10_1101-2021_01_07_425675 4 1 Here here RB 10_1101-2021_01_07_425675 4 2 we -PRON- PRP 10_1101-2021_01_07_425675 4 3 demonstrate demonstrate VBP 10_1101-2021_01_07_425675 4 4 a a DT 10_1101-2021_01_07_425675 4 5 20 20 CD 10_1101-2021_01_07_425675 4 6 method method NN 10_1101-2021_01_07_425675 4 7 for for IN 10_1101-2021_01_07_425675 4 8 direct direct JJ 10_1101-2021_01_07_425675 4 9 de de FW 10_1101-2021_01_07_425675 4 10 novo novo NNP 10_1101-2021_01_07_425675 4 11 sequencing sequencing NN 10_1101-2021_01_07_425675 4 12 of of IN 10_1101-2021_01_07_425675 4 13 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 4 14 IgG IgG NNP 10_1101-2021_01_07_425675 4 15 from from IN 10_1101-2021_01_07_425675 4 16 the the DT 10_1101-2021_01_07_425675 4 17 purified purified JJ 10_1101-2021_01_07_425675 4 18 antibody antibody NN 10_1101-2021_01_07_425675 4 19 products product NNS 10_1101-2021_01_07_425675 4 20 . . . 10_1101-2021_01_07_425675 5 1 The the DT 10_1101-2021_01_07_425675 5 2 21 21 CD 10_1101-2021_01_07_425675 5 3 method method NN 10_1101-2021_01_07_425675 5 4 uses use VBZ 10_1101-2021_01_07_425675 5 5 a a DT 10_1101-2021_01_07_425675 5 6 panel panel NN 10_1101-2021_01_07_425675 5 7 of of IN 10_1101-2021_01_07_425675 5 8 multiple multiple JJ 10_1101-2021_01_07_425675 5 9 complementary complementary JJ 10_1101-2021_01_07_425675 5 10 proteases protease NNS 10_1101-2021_01_07_425675 5 11 to to TO 10_1101-2021_01_07_425675 5 12 generate generate VB 10_1101-2021_01_07_425675 5 13 suitable suitable JJ 10_1101-2021_01_07_425675 5 14 peptides peptide NNS 10_1101-2021_01_07_425675 5 15 for for IN 10_1101-2021_01_07_425675 5 16 de de NNP 10_1101-2021_01_07_425675 5 17 22 22 CD 10_1101-2021_01_07_425675 5 18 novo novo NNP 10_1101-2021_01_07_425675 5 19 sequencing sequencing NN 10_1101-2021_01_07_425675 5 20 by by IN 10_1101-2021_01_07_425675 5 21 LC LC NNP 10_1101-2021_01_07_425675 5 22 - - HYPH 10_1101-2021_01_07_425675 5 23 MS MS NNP 10_1101-2021_01_07_425675 5 24 / / SYM 10_1101-2021_01_07_425675 5 25 MS MS NNP 10_1101-2021_01_07_425675 5 26 in in IN 10_1101-2021_01_07_425675 5 27 a a DT 10_1101-2021_01_07_425675 5 28 bottom bottom NN 10_1101-2021_01_07_425675 5 29 - - HYPH 10_1101-2021_01_07_425675 5 30 up up RP 10_1101-2021_01_07_425675 5 31 fashion fashion NN 10_1101-2021_01_07_425675 5 32 . . . 10_1101-2021_01_07_425675 6 1 Furthermore furthermore RB 10_1101-2021_01_07_425675 6 2 , , , 10_1101-2021_01_07_425675 6 3 we -PRON- PRP 10_1101-2021_01_07_425675 6 4 apply apply VBP 10_1101-2021_01_07_425675 6 5 a a DT 10_1101-2021_01_07_425675 6 6 dual dual JJ 10_1101-2021_01_07_425675 6 7 23 23 CD 10_1101-2021_01_07_425675 6 8 fragmentation fragmentation NN 10_1101-2021_01_07_425675 6 9 scheme scheme NN 10_1101-2021_01_07_425675 6 10 , , , 10_1101-2021_01_07_425675 6 11 using use VBG 10_1101-2021_01_07_425675 6 12 both both DT 10_1101-2021_01_07_425675 6 13 stepped step VBD 10_1101-2021_01_07_425675 6 14 high high JJ 10_1101-2021_01_07_425675 6 15 - - HYPH 10_1101-2021_01_07_425675 6 16 energy energy NN 10_1101-2021_01_07_425675 6 17 collision collision NN 10_1101-2021_01_07_425675 6 18 dissociation dissociation NN 10_1101-2021_01_07_425675 6 19 ( ( -LRB- 10_1101-2021_01_07_425675 6 20 stepped step VBD 10_1101-2021_01_07_425675 6 21 HCD HCD NNP 10_1101-2021_01_07_425675 6 22 ) ) -RRB- 10_1101-2021_01_07_425675 6 23 and and CC 10_1101-2021_01_07_425675 6 24 24 24 CD 10_1101-2021_01_07_425675 6 25 electron electron NN 10_1101-2021_01_07_425675 6 26 transfer transfer NN 10_1101-2021_01_07_425675 6 27 high high JJ 10_1101-2021_01_07_425675 6 28 - - HYPH 10_1101-2021_01_07_425675 6 29 energy energy NN 10_1101-2021_01_07_425675 6 30 collision collision NN 10_1101-2021_01_07_425675 6 31 dissociation dissociation NN 10_1101-2021_01_07_425675 6 32 ( ( -LRB- 10_1101-2021_01_07_425675 6 33 EThcD EThcD NNP 10_1101-2021_01_07_425675 6 34 ) ) -RRB- 10_1101-2021_01_07_425675 6 35 on on IN 10_1101-2021_01_07_425675 6 36 all all DT 10_1101-2021_01_07_425675 6 37 peptide peptide JJ 10_1101-2021_01_07_425675 6 38 precursors precursor NNS 10_1101-2021_01_07_425675 6 39 . . . 10_1101-2021_01_07_425675 7 1 The the DT 10_1101-2021_01_07_425675 7 2 method method NN 10_1101-2021_01_07_425675 7 3 25 25 CD 10_1101-2021_01_07_425675 7 4 achieves achieve VBZ 10_1101-2021_01_07_425675 7 5 full full JJ 10_1101-2021_01_07_425675 7 6 sequence sequence NN 10_1101-2021_01_07_425675 7 7 coverage coverage NN 10_1101-2021_01_07_425675 7 8 of of IN 10_1101-2021_01_07_425675 7 9 the the DT 10_1101-2021_01_07_425675 7 10 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 7 11 antibody antibody NN 10_1101-2021_01_07_425675 7 12 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 7 13 , , , 10_1101-2021_01_07_425675 7 14 with with IN 10_1101-2021_01_07_425675 7 15 an an DT 10_1101-2021_01_07_425675 7 16 accuracy accuracy NN 10_1101-2021_01_07_425675 7 17 of of IN 10_1101-2021_01_07_425675 7 18 99 99 CD 10_1101-2021_01_07_425675 7 19 % % NN 10_1101-2021_01_07_425675 7 20 26 26 CD 10_1101-2021_01_07_425675 7 21 in in IN 10_1101-2021_01_07_425675 7 22 the the DT 10_1101-2021_01_07_425675 7 23 variable variable JJ 10_1101-2021_01_07_425675 7 24 regions region NNS 10_1101-2021_01_07_425675 7 25 . . . 10_1101-2021_01_07_425675 8 1 We -PRON- PRP 10_1101-2021_01_07_425675 8 2 applied apply VBD 10_1101-2021_01_07_425675 8 3 the the DT 10_1101-2021_01_07_425675 8 4 method method NN 10_1101-2021_01_07_425675 8 5 to to TO 10_1101-2021_01_07_425675 8 6 sequence sequence VB 10_1101-2021_01_07_425675 8 7 the the DT 10_1101-2021_01_07_425675 8 8 widely widely RB 10_1101-2021_01_07_425675 8 9 used use VBN 10_1101-2021_01_07_425675 8 10 anti anti JJ 10_1101-2021_01_07_425675 8 11 - - JJ 10_1101-2021_01_07_425675 8 12 FLAG FLAG NNP 10_1101-2021_01_07_425675 8 13 - - HYPH 10_1101-2021_01_07_425675 8 14 M2 M2 NNP 10_1101-2021_01_07_425675 8 15 mouse mouse NN 10_1101-2021_01_07_425675 8 16 27 27 CD 10_1101-2021_01_07_425675 8 17 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 8 18 antibody antibody NN 10_1101-2021_01_07_425675 8 19 , , , 10_1101-2021_01_07_425675 8 20 which which WDT 10_1101-2021_01_07_425675 8 21 we -PRON- PRP 10_1101-2021_01_07_425675 8 22 successfully successfully RB 10_1101-2021_01_07_425675 8 23 validated validate VBD 10_1101-2021_01_07_425675 8 24 by by IN 10_1101-2021_01_07_425675 8 25 remodeling remodel VBG 10_1101-2021_01_07_425675 8 26 a a DT 10_1101-2021_01_07_425675 8 27 high high JJ 10_1101-2021_01_07_425675 8 28 - - HYPH 10_1101-2021_01_07_425675 8 29 resolution resolution NN 10_1101-2021_01_07_425675 8 30 crystal crystal NN 10_1101-2021_01_07_425675 8 31 28 28 CD 10_1101-2021_01_07_425675 8 32 structure structure NN 10_1101-2021_01_07_425675 8 33 of of IN 10_1101-2021_01_07_425675 8 34 the the DT 10_1101-2021_01_07_425675 8 35 Fab Fab NNP 10_1101-2021_01_07_425675 8 36 and and CC 10_1101-2021_01_07_425675 8 37 demonstrating demonstrate VBG 10_1101-2021_01_07_425675 8 38 binding bind VBG 10_1101-2021_01_07_425675 8 39 to to IN 10_1101-2021_01_07_425675 8 40 a a DT 10_1101-2021_01_07_425675 8 41 FLAG FLAG NNP 10_1101-2021_01_07_425675 8 42 - - HYPH 10_1101-2021_01_07_425675 8 43 tagged tag VBN 10_1101-2021_01_07_425675 8 44 target target NN 10_1101-2021_01_07_425675 8 45 protein protein NN 10_1101-2021_01_07_425675 8 46 in in IN 10_1101-2021_01_07_425675 8 47 Western western JJ 10_1101-2021_01_07_425675 8 48 blot blot NN 10_1101-2021_01_07_425675 8 49 29 29 CD 10_1101-2021_01_07_425675 8 50 analysis analysis NN 10_1101-2021_01_07_425675 8 51 . . . 10_1101-2021_01_07_425675 9 1 The the DT 10_1101-2021_01_07_425675 9 2 method method NN 10_1101-2021_01_07_425675 9 3 thus thus RB 10_1101-2021_01_07_425675 9 4 offers offer VBZ 10_1101-2021_01_07_425675 9 5 robust robust JJ 10_1101-2021_01_07_425675 9 6 and and CC 10_1101-2021_01_07_425675 9 7 reliable reliable JJ 10_1101-2021_01_07_425675 9 8 sequences sequence NNS 10_1101-2021_01_07_425675 9 9 of of IN 10_1101-2021_01_07_425675 9 10 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 9 11 antibodies antibody NNS 10_1101-2021_01_07_425675 9 12 . . . 10_1101-2021_01_07_425675 10 1 30 30 CD 10_1101-2021_01_07_425675 10 2 .CC .CC : 10_1101-2021_01_07_425675 10 3 - - : 10_1101-2021_01_07_425675 10 4 BY by IN 10_1101-2021_01_07_425675 10 5 4.0 4.0 CD 10_1101-2021_01_07_425675 10 6 International International NNP 10_1101-2021_01_07_425675 10 7 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 10 8 under under IN 10_1101-2021_01_07_425675 10 9 a a DT 10_1101-2021_01_07_425675 10 10 ( ( -LRB- 10_1101-2021_01_07_425675 10 11 which which WDT 10_1101-2021_01_07_425675 10 12 was be VBD 10_1101-2021_01_07_425675 10 13 not not RB 10_1101-2021_01_07_425675 10 14 certified certify VBN 10_1101-2021_01_07_425675 10 15 by by IN 10_1101-2021_01_07_425675 10 16 peer peer NN 10_1101-2021_01_07_425675 10 17 review review NN 10_1101-2021_01_07_425675 10 18 ) ) -RRB- 10_1101-2021_01_07_425675 10 19 is be VBZ 10_1101-2021_01_07_425675 10 20 the the DT 10_1101-2021_01_07_425675 10 21 author author NN 10_1101-2021_01_07_425675 10 22 / / SYM 10_1101-2021_01_07_425675 10 23 funder funder NN 10_1101-2021_01_07_425675 10 24 , , , 10_1101-2021_01_07_425675 10 25 who who WP 10_1101-2021_01_07_425675 10 26 has have VBZ 10_1101-2021_01_07_425675 10 27 granted grant VBN 10_1101-2021_01_07_425675 10 28 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 10 29 a a DT 10_1101-2021_01_07_425675 10 30 license license NN 10_1101-2021_01_07_425675 10 31 to to TO 10_1101-2021_01_07_425675 10 32 display display VB 10_1101-2021_01_07_425675 10 33 the the DT 10_1101-2021_01_07_425675 10 34 preprint preprint NN 10_1101-2021_01_07_425675 10 35 in in IN 10_1101-2021_01_07_425675 10 36 perpetuity perpetuity NN 10_1101-2021_01_07_425675 10 37 . . . 10_1101-2021_01_07_425675 11 1 It -PRON- PRP 10_1101-2021_01_07_425675 11 2 is be VBZ 10_1101-2021_01_07_425675 11 3 made make VBN 10_1101-2021_01_07_425675 11 4 The the DT 10_1101-2021_01_07_425675 11 5 copyright copyright NN 10_1101-2021_01_07_425675 11 6 holder holder NN 10_1101-2021_01_07_425675 11 7 for for IN 10_1101-2021_01_07_425675 11 8 this this DT 10_1101-2021_01_07_425675 11 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 11 10 version version NN 10_1101-2021_01_07_425675 11 11 posted post VBD 10_1101-2021_01_07_425675 11 12 January January NNP 10_1101-2021_01_07_425675 11 13 8 8 CD 10_1101-2021_01_07_425675 11 14 , , , 10_1101-2021_01_07_425675 11 15 2021 2021 CD 10_1101-2021_01_07_425675 11 16 . . . 10_1101-2021_01_07_425675 11 17 ; ; : 10_1101-2021_01_07_425675 11 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 11 19 : : : 10_1101-2021_01_07_425675 11 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 11 21 preprint preprint NN 10_1101-2021_01_07_425675 11 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 11 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 11 24 3 3 CD 10_1101-2021_01_07_425675 11 25 Introduction introduction NN 10_1101-2021_01_07_425675 11 26 31 31 CD 10_1101-2021_01_07_425675 11 27 Antibodies Antibodies NNPS 10_1101-2021_01_07_425675 11 28 can can MD 10_1101-2021_01_07_425675 11 29 bind bind VB 10_1101-2021_01_07_425675 11 30 a a DT 10_1101-2021_01_07_425675 11 31 great great JJ 10_1101-2021_01_07_425675 11 32 molecular molecular JJ 10_1101-2021_01_07_425675 11 33 diversity diversity NN 10_1101-2021_01_07_425675 11 34 of of IN 10_1101-2021_01_07_425675 11 35 antigens antigen NNS 10_1101-2021_01_07_425675 11 36 , , , 10_1101-2021_01_07_425675 11 37 owing owe VBG 10_1101-2021_01_07_425675 11 38 to to IN 10_1101-2021_01_07_425675 11 39 the the DT 10_1101-2021_01_07_425675 11 40 high high JJ 10_1101-2021_01_07_425675 11 41 degree degree NN 10_1101-2021_01_07_425675 11 42 of of IN 10_1101-2021_01_07_425675 11 43 sequence sequence NN 10_1101-2021_01_07_425675 11 44 32 32 CD 10_1101-2021_01_07_425675 11 45 diversity diversity NN 10_1101-2021_01_07_425675 11 46 that that WDT 10_1101-2021_01_07_425675 11 47 is be VBZ 10_1101-2021_01_07_425675 11 48 available available JJ 10_1101-2021_01_07_425675 11 49 through through IN 10_1101-2021_01_07_425675 11 50 somatic somatic JJ 10_1101-2021_01_07_425675 11 51 recombination recombination NN 10_1101-2021_01_07_425675 11 52 , , , 10_1101-2021_01_07_425675 11 53 hypermutation hypermutation NN 10_1101-2021_01_07_425675 11 54 , , , 10_1101-2021_01_07_425675 11 55 and and CC 10_1101-2021_01_07_425675 11 56 heavy heavy JJ 10_1101-2021_01_07_425675 11 57 - - HYPH 10_1101-2021_01_07_425675 11 58 light light NN 10_1101-2021_01_07_425675 11 59 chain chain NN 10_1101-2021_01_07_425675 11 60 33 33 CD 10_1101-2021_01_07_425675 11 61 pairings pairing NNS 10_1101-2021_01_07_425675 11 62 1 1 CD 10_1101-2021_01_07_425675 11 63 - - SYM 10_1101-2021_01_07_425675 11 64 2 2 CD 10_1101-2021_01_07_425675 11 65 . . . 10_1101-2021_01_07_425675 12 1 Sequence sequence NN 10_1101-2021_01_07_425675 12 2 information information NN 10_1101-2021_01_07_425675 12 3 on on IN 10_1101-2021_01_07_425675 12 4 antibodies antibody NNS 10_1101-2021_01_07_425675 12 5 therefore therefore RB 10_1101-2021_01_07_425675 12 6 is be VBZ 10_1101-2021_01_07_425675 12 7 crucial crucial JJ 10_1101-2021_01_07_425675 12 8 to to IN 10_1101-2021_01_07_425675 12 9 understanding understand VBG 10_1101-2021_01_07_425675 12 10 the the DT 10_1101-2021_01_07_425675 12 11 34 34 CD 10_1101-2021_01_07_425675 12 12 structural structural JJ 10_1101-2021_01_07_425675 12 13 basis basis NN 10_1101-2021_01_07_425675 12 14 of of IN 10_1101-2021_01_07_425675 12 15 antigen antigen NNP 10_1101-2021_01_07_425675 12 16 binding bind VBG 10_1101-2021_01_07_425675 12 17 , , , 10_1101-2021_01_07_425675 12 18 how how WRB 10_1101-2021_01_07_425675 12 19 somatic somatic JJ 10_1101-2021_01_07_425675 12 20 hypermutation hypermutation NN 10_1101-2021_01_07_425675 12 21 governs govern VBZ 10_1101-2021_01_07_425675 12 22 affinity affinity NNP 10_1101-2021_01_07_425675 12 23 maturation maturation NNP 10_1101-2021_01_07_425675 12 24 , , , 10_1101-2021_01_07_425675 12 25 and and CC 10_1101-2021_01_07_425675 12 26 35 35 CD 10_1101-2021_01_07_425675 12 27 an an DT 10_1101-2021_01_07_425675 12 28 overall overall JJ 10_1101-2021_01_07_425675 12 29 understanding understanding NN 10_1101-2021_01_07_425675 12 30 of of IN 10_1101-2021_01_07_425675 12 31 the the DT 10_1101-2021_01_07_425675 12 32 adaptive adaptive JJ 10_1101-2021_01_07_425675 12 33 immune immune JJ 10_1101-2021_01_07_425675 12 34 response response NN 10_1101-2021_01_07_425675 12 35 in in IN 10_1101-2021_01_07_425675 12 36 health health NN 10_1101-2021_01_07_425675 12 37 and and CC 10_1101-2021_01_07_425675 12 38 disease disease NN 10_1101-2021_01_07_425675 12 39 , , , 10_1101-2021_01_07_425675 12 40 by by IN 10_1101-2021_01_07_425675 12 41 mapping map VBG 10_1101-2021_01_07_425675 12 42 36 36 CD 10_1101-2021_01_07_425675 12 43 out out IN 10_1101-2021_01_07_425675 12 44 the the DT 10_1101-2021_01_07_425675 12 45 antibody antibody NN 10_1101-2021_01_07_425675 12 46 repertoire repertoire NN 10_1101-2021_01_07_425675 12 47 . . . 10_1101-2021_01_07_425675 13 1 Moreover moreover RB 10_1101-2021_01_07_425675 13 2 , , , 10_1101-2021_01_07_425675 13 3 antibodies antibody NNS 10_1101-2021_01_07_425675 13 4 have have VBP 10_1101-2021_01_07_425675 13 5 become become VBN 10_1101-2021_01_07_425675 13 6 invaluable invaluable JJ 10_1101-2021_01_07_425675 13 7 research research NN 10_1101-2021_01_07_425675 13 8 tools tool NNS 10_1101-2021_01_07_425675 13 9 in in IN 10_1101-2021_01_07_425675 13 10 the the DT 10_1101-2021_01_07_425675 13 11 37 37 CD 10_1101-2021_01_07_425675 13 12 life life NN 10_1101-2021_01_07_425675 13 13 sciences science NNS 10_1101-2021_01_07_425675 13 14 and and CC 10_1101-2021_01_07_425675 13 15 ever ever RB 10_1101-2021_01_07_425675 13 16 more more RBR 10_1101-2021_01_07_425675 13 17 widely widely RB 10_1101-2021_01_07_425675 13 18 developed develop VBN 10_1101-2021_01_07_425675 13 19 as as IN 10_1101-2021_01_07_425675 13 20 therapeutic therapeutic JJ 10_1101-2021_01_07_425675 13 21 agents agent NNS 10_1101-2021_01_07_425675 13 22 3 3 CD 10_1101-2021_01_07_425675 13 23 - - SYM 10_1101-2021_01_07_425675 13 24 4 4 CD 10_1101-2021_01_07_425675 13 25 . . . 10_1101-2021_01_07_425675 14 1 In in IN 10_1101-2021_01_07_425675 14 2 this this DT 10_1101-2021_01_07_425675 14 3 context context NN 10_1101-2021_01_07_425675 14 4 , , , 10_1101-2021_01_07_425675 14 5 sequence sequence VB 10_1101-2021_01_07_425675 14 6 38 38 CD 10_1101-2021_01_07_425675 14 7 information information NN 10_1101-2021_01_07_425675 14 8 is be VBZ 10_1101-2021_01_07_425675 14 9 crucial crucial JJ 10_1101-2021_01_07_425675 14 10 for for IN 10_1101-2021_01_07_425675 14 11 the the DT 10_1101-2021_01_07_425675 14 12 use use NN 10_1101-2021_01_07_425675 14 13 , , , 10_1101-2021_01_07_425675 14 14 production production NN 10_1101-2021_01_07_425675 14 15 and and CC 10_1101-2021_01_07_425675 14 16 validation validation NN 10_1101-2021_01_07_425675 14 17 of of IN 10_1101-2021_01_07_425675 14 18 these these DT 10_1101-2021_01_07_425675 14 19 important important JJ 10_1101-2021_01_07_425675 14 20 research research NN 10_1101-2021_01_07_425675 14 21 tools tool NNS 10_1101-2021_01_07_425675 14 22 and and CC 10_1101-2021_01_07_425675 14 23 39 39 CD 10_1101-2021_01_07_425675 14 24 biopharmaceutical biopharmaceutical JJ 10_1101-2021_01_07_425675 14 25 agents agent NNS 10_1101-2021_01_07_425675 14 26 5 5 CD 10_1101-2021_01_07_425675 14 27 - - SYM 10_1101-2021_01_07_425675 14 28 6 6 CD 10_1101-2021_01_07_425675 14 29 . . . 10_1101-2021_01_07_425675 15 1 40 40 CD 10_1101-2021_01_07_425675 15 2 Antibody antibody NN 10_1101-2021_01_07_425675 15 3 sequences sequence NNS 10_1101-2021_01_07_425675 15 4 are be VBP 10_1101-2021_01_07_425675 15 5 typically typically RB 10_1101-2021_01_07_425675 15 6 obtained obtain VBN 10_1101-2021_01_07_425675 15 7 through through IN 10_1101-2021_01_07_425675 15 8 cloning clone VBG 10_1101-2021_01_07_425675 15 9 and and CC 10_1101-2021_01_07_425675 15 10 sequencing sequencing NN 10_1101-2021_01_07_425675 15 11 of of IN 10_1101-2021_01_07_425675 15 12 the the DT 10_1101-2021_01_07_425675 15 13 coding coding NN 10_1101-2021_01_07_425675 15 14 mRNAs mrnas $ 10_1101-2021_01_07_425675 15 15 41 41 CD 10_1101-2021_01_07_425675 15 16 of of IN 10_1101-2021_01_07_425675 15 17 the the DT 10_1101-2021_01_07_425675 15 18 paired pair VBN 10_1101-2021_01_07_425675 15 19 heavy heavy JJ 10_1101-2021_01_07_425675 15 20 and and CC 10_1101-2021_01_07_425675 15 21 light light JJ 10_1101-2021_01_07_425675 15 22 chains chain NNS 10_1101-2021_01_07_425675 15 23 7 7 CD 10_1101-2021_01_07_425675 15 24 - - SYM 10_1101-2021_01_07_425675 15 25 9 9 CD 10_1101-2021_01_07_425675 15 26 . . . 10_1101-2021_01_07_425675 16 1 The the DT 10_1101-2021_01_07_425675 16 2 sequencing sequencing NN 10_1101-2021_01_07_425675 16 3 workflows workflow NNS 10_1101-2021_01_07_425675 16 4 thereby thereby RB 10_1101-2021_01_07_425675 16 5 rely rely VBP 10_1101-2021_01_07_425675 16 6 on on IN 10_1101-2021_01_07_425675 16 7 isolation isolation NN 10_1101-2021_01_07_425675 16 8 of of IN 10_1101-2021_01_07_425675 16 9 the the DT 10_1101-2021_01_07_425675 16 10 42 42 CD 10_1101-2021_01_07_425675 16 11 antibody antibody NN 10_1101-2021_01_07_425675 16 12 - - HYPH 10_1101-2021_01_07_425675 16 13 producing produce VBG 10_1101-2021_01_07_425675 16 14 cells cell NNS 10_1101-2021_01_07_425675 16 15 from from IN 10_1101-2021_01_07_425675 16 16 peripheral peripheral JJ 10_1101-2021_01_07_425675 16 17 blood blood NN 10_1101-2021_01_07_425675 16 18 monocytes monocyte NNS 10_1101-2021_01_07_425675 16 19 , , , 10_1101-2021_01_07_425675 16 20 or or CC 10_1101-2021_01_07_425675 16 21 spleen spleen NN 10_1101-2021_01_07_425675 16 22 and and CC 10_1101-2021_01_07_425675 16 23 bone bone NN 10_1101-2021_01_07_425675 16 24 marrow marrow NN 10_1101-2021_01_07_425675 16 25 tissues tissue NNS 10_1101-2021_01_07_425675 16 26 . . . 10_1101-2021_01_07_425675 17 1 43 43 CD 10_1101-2021_01_07_425675 17 2 These these DT 10_1101-2021_01_07_425675 17 3 antibody antibody NN 10_1101-2021_01_07_425675 17 4 - - HYPH 10_1101-2021_01_07_425675 17 5 producing produce VBG 10_1101-2021_01_07_425675 17 6 cells cell NNS 10_1101-2021_01_07_425675 17 7 are be VBP 10_1101-2021_01_07_425675 17 8 not not RB 10_1101-2021_01_07_425675 17 9 always always RB 10_1101-2021_01_07_425675 17 10 readily readily RB 10_1101-2021_01_07_425675 17 11 available available JJ 10_1101-2021_01_07_425675 17 12 however however RB 10_1101-2021_01_07_425675 17 13 , , , 10_1101-2021_01_07_425675 17 14 and and CC 10_1101-2021_01_07_425675 17 15 cloning clone VBG 10_1101-2021_01_07_425675 17 16 / / SYM 10_1101-2021_01_07_425675 17 17 sequencing sequence VBG 10_1101-2021_01_07_425675 17 18 44 44 CD 10_1101-2021_01_07_425675 17 19 of of IN 10_1101-2021_01_07_425675 17 20 the the DT 10_1101-2021_01_07_425675 17 21 paired pair VBN 10_1101-2021_01_07_425675 17 22 heavy heavy JJ 10_1101-2021_01_07_425675 17 23 and and CC 10_1101-2021_01_07_425675 17 24 light light JJ 10_1101-2021_01_07_425675 17 25 chains chain NNS 10_1101-2021_01_07_425675 17 26 is be VBZ 10_1101-2021_01_07_425675 17 27 a a DT 10_1101-2021_01_07_425675 17 28 non non JJ 10_1101-2021_01_07_425675 17 29 - - JJ 10_1101-2021_01_07_425675 17 30 trivial trivial JJ 10_1101-2021_01_07_425675 17 31 task task NN 10_1101-2021_01_07_425675 17 32 with with IN 10_1101-2021_01_07_425675 17 33 a a DT 10_1101-2021_01_07_425675 17 34 limited limited JJ 10_1101-2021_01_07_425675 17 35 success success NN 10_1101-2021_01_07_425675 17 36 rate rate NN 10_1101-2021_01_07_425675 17 37 7 7 CD 10_1101-2021_01_07_425675 17 38 - - SYM 10_1101-2021_01_07_425675 17 39 9 9 CD 10_1101-2021_01_07_425675 17 40 . . . 10_1101-2021_01_07_425675 18 1 Moreover moreover RB 10_1101-2021_01_07_425675 18 2 , , , 10_1101-2021_01_07_425675 18 3 45 45 CD 10_1101-2021_01_07_425675 18 4 antibodies antibody NNS 10_1101-2021_01_07_425675 18 5 are be VBP 10_1101-2021_01_07_425675 18 6 secreted secrete VBN 10_1101-2021_01_07_425675 18 7 in in IN 10_1101-2021_01_07_425675 18 8 bodily bodily NNP 10_1101-2021_01_07_425675 18 9 fluids fluid NNS 10_1101-2021_01_07_425675 18 10 and and CC 10_1101-2021_01_07_425675 18 11 mucus mucus NNP 10_1101-2021_01_07_425675 18 12 . . . 10_1101-2021_01_07_425675 19 1 Antibodies antibody NNS 10_1101-2021_01_07_425675 19 2 are be VBP 10_1101-2021_01_07_425675 19 3 thereby thereby RB 10_1101-2021_01_07_425675 19 4 in in IN 10_1101-2021_01_07_425675 19 5 large large JJ 10_1101-2021_01_07_425675 19 6 part part NN 10_1101-2021_01_07_425675 19 7 46 46 CD 10_1101-2021_01_07_425675 19 8 functionally functionally RB 10_1101-2021_01_07_425675 19 9 disconnected disconnect VBN 10_1101-2021_01_07_425675 19 10 from from IN 10_1101-2021_01_07_425675 19 11 their -PRON- PRP$ 10_1101-2021_01_07_425675 19 12 producing produce VBG 10_1101-2021_01_07_425675 19 13 B b NN 10_1101-2021_01_07_425675 19 14 - - HYPH 10_1101-2021_01_07_425675 19 15 cell cell NN 10_1101-2021_01_07_425675 19 16 , , , 10_1101-2021_01_07_425675 19 17 which which WDT 10_1101-2021_01_07_425675 19 18 raises raise VBZ 10_1101-2021_01_07_425675 19 19 questions question NNS 10_1101-2021_01_07_425675 19 20 on on IN 10_1101-2021_01_07_425675 19 21 how how WRB 10_1101-2021_01_07_425675 19 22 the the DT 10_1101-2021_01_07_425675 19 23 secreted secreted JJ 10_1101-2021_01_07_425675 19 24 47 47 CD 10_1101-2021_01_07_425675 19 25 antibody antibody NN 10_1101-2021_01_07_425675 19 26 pool pool NN 10_1101-2021_01_07_425675 19 27 relates relate VBZ 10_1101-2021_01_07_425675 19 28 quantitatively quantitatively RB 10_1101-2021_01_07_425675 19 29 to to IN 10_1101-2021_01_07_425675 19 30 the the DT 10_1101-2021_01_07_425675 19 31 underlying underlie VBG 10_1101-2021_01_07_425675 19 32 B b NN 10_1101-2021_01_07_425675 19 33 - - HYPH 10_1101-2021_01_07_425675 19 34 cell cell NN 10_1101-2021_01_07_425675 19 35 population population NN 10_1101-2021_01_07_425675 19 36 and and CC 10_1101-2021_01_07_425675 19 37 whether whether IN 10_1101-2021_01_07_425675 19 38 there there EX 10_1101-2021_01_07_425675 19 39 are be VBP 10_1101-2021_01_07_425675 19 40 48 48 CD 10_1101-2021_01_07_425675 19 41 potential potential JJ 10_1101-2021_01_07_425675 19 42 sampling sample VBG 10_1101-2021_01_07_425675 19 43 biases bias NNS 10_1101-2021_01_07_425675 19 44 in in IN 10_1101-2021_01_07_425675 19 45 current current JJ 10_1101-2021_01_07_425675 19 46 antibody antibody NN 10_1101-2021_01_07_425675 19 47 sequencing sequencing NN 10_1101-2021_01_07_425675 19 48 strategies strategy NNS 10_1101-2021_01_07_425675 19 49 . . . 10_1101-2021_01_07_425675 20 1 49 49 CD 10_1101-2021_01_07_425675 20 2 Direct direct JJ 10_1101-2021_01_07_425675 20 3 mass mass NN 10_1101-2021_01_07_425675 20 4 spectrometry spectrometry NN 10_1101-2021_01_07_425675 20 5 ( ( -LRB- 10_1101-2021_01_07_425675 20 6 MS)-based ms)-base VBN 10_1101-2021_01_07_425675 20 7 sequencing sequencing NN 10_1101-2021_01_07_425675 20 8 of of IN 10_1101-2021_01_07_425675 20 9 the the DT 10_1101-2021_01_07_425675 20 10 secreted secrete VBN 10_1101-2021_01_07_425675 20 11 antibody antibody NN 10_1101-2021_01_07_425675 20 12 products product NNS 10_1101-2021_01_07_425675 20 13 is be VBZ 10_1101-2021_01_07_425675 20 14 a a DT 10_1101-2021_01_07_425675 20 15 useful useful JJ 10_1101-2021_01_07_425675 20 16 50 50 CD 10_1101-2021_01_07_425675 20 17 complementary complementary JJ 10_1101-2021_01_07_425675 20 18 tool tool NN 10_1101-2021_01_07_425675 20 19 that that WDT 10_1101-2021_01_07_425675 20 20 can can MD 10_1101-2021_01_07_425675 20 21 address address VB 10_1101-2021_01_07_425675 20 22 some some DT 10_1101-2021_01_07_425675 20 23 of of IN 10_1101-2021_01_07_425675 20 24 the the DT 10_1101-2021_01_07_425675 20 25 challenges challenge NNS 10_1101-2021_01_07_425675 20 26 faced face VBN 10_1101-2021_01_07_425675 20 27 by by IN 10_1101-2021_01_07_425675 20 28 conventional conventional JJ 10_1101-2021_01_07_425675 20 29 sequencing sequence VBG 10_1101-2021_01_07_425675 20 30 51 51 CD 10_1101-2021_01_07_425675 20 31 strategies strategy NNS 10_1101-2021_01_07_425675 20 32 relying rely VBG 10_1101-2021_01_07_425675 20 33 on on IN 10_1101-2021_01_07_425675 20 34 cloning clone VBG 10_1101-2021_01_07_425675 20 35 / / SYM 10_1101-2021_01_07_425675 20 36 sequencing sequencing NN 10_1101-2021_01_07_425675 20 37 of of IN 10_1101-2021_01_07_425675 20 38 the the DT 10_1101-2021_01_07_425675 20 39 coding coding JJ 10_1101-2021_01_07_425675 20 40 mRNAs mrnas $ 10_1101-2021_01_07_425675 20 41 10 10 CD 10_1101-2021_01_07_425675 20 42 - - SYM 10_1101-2021_01_07_425675 20 43 17 17 CD 10_1101-2021_01_07_425675 20 44 . . . 10_1101-2021_01_07_425675 21 1 MS MS NNP 10_1101-2021_01_07_425675 21 2 - - HYPH 10_1101-2021_01_07_425675 21 3 based base VBN 10_1101-2021_01_07_425675 21 4 methods method NNS 10_1101-2021_01_07_425675 21 5 do do VBP 10_1101-2021_01_07_425675 21 6 not not RB 10_1101-2021_01_07_425675 21 7 52 52 CD 10_1101-2021_01_07_425675 21 8 rely rely VB 10_1101-2021_01_07_425675 21 9 on on IN 10_1101-2021_01_07_425675 21 10 the the DT 10_1101-2021_01_07_425675 21 11 availability availability NN 10_1101-2021_01_07_425675 21 12 of of IN 10_1101-2021_01_07_425675 21 13 the the DT 10_1101-2021_01_07_425675 21 14 antibody antibody NN 10_1101-2021_01_07_425675 21 15 - - HYPH 10_1101-2021_01_07_425675 21 16 producing produce VBG 10_1101-2021_01_07_425675 21 17 cells cell NNS 10_1101-2021_01_07_425675 21 18 , , , 10_1101-2021_01_07_425675 21 19 but but CC 10_1101-2021_01_07_425675 21 20 rather rather RB 10_1101-2021_01_07_425675 21 21 target target VB 10_1101-2021_01_07_425675 21 22 the the DT 10_1101-2021_01_07_425675 21 23 polypeptide polypeptide NN 10_1101-2021_01_07_425675 21 24 products product NNS 10_1101-2021_01_07_425675 21 25 53 53 CD 10_1101-2021_01_07_425675 21 26 directly directly RB 10_1101-2021_01_07_425675 21 27 , , , 10_1101-2021_01_07_425675 21 28 offering offer VBG 10_1101-2021_01_07_425675 21 29 the the DT 10_1101-2021_01_07_425675 21 30 prospect prospect NN 10_1101-2021_01_07_425675 21 31 of of IN 10_1101-2021_01_07_425675 21 32 a a DT 10_1101-2021_01_07_425675 21 33 next next JJ 10_1101-2021_01_07_425675 21 34 generation generation NN 10_1101-2021_01_07_425675 21 35 of of IN 10_1101-2021_01_07_425675 21 36 serology serology NN 10_1101-2021_01_07_425675 21 37 , , , 10_1101-2021_01_07_425675 21 38 in in IN 10_1101-2021_01_07_425675 21 39 which which WDT 10_1101-2021_01_07_425675 21 40 secreted secrete VBD 10_1101-2021_01_07_425675 21 41 antibody antibody NN 10_1101-2021_01_07_425675 21 42 54 54 CD 10_1101-2021_01_07_425675 21 43 sequences sequence NNS 10_1101-2021_01_07_425675 21 44 might may MD 10_1101-2021_01_07_425675 21 45 be be VB 10_1101-2021_01_07_425675 21 46 obtained obtain VBN 10_1101-2021_01_07_425675 21 47 from from IN 10_1101-2021_01_07_425675 21 48 any any DT 10_1101-2021_01_07_425675 21 49 bodily bodily JJ 10_1101-2021_01_07_425675 21 50 fluid fluid NN 10_1101-2021_01_07_425675 21 51 . . . 10_1101-2021_01_07_425675 22 1 Whereas whereas IN 10_1101-2021_01_07_425675 22 2 MS MS NNP 10_1101-2021_01_07_425675 22 3 - - HYPH 10_1101-2021_01_07_425675 22 4 based base VBN 10_1101-2021_01_07_425675 22 5 de de NNP 10_1101-2021_01_07_425675 22 6 novo novo NNP 10_1101-2021_01_07_425675 22 7 sequencing sequencing NN 10_1101-2021_01_07_425675 22 8 still still RB 10_1101-2021_01_07_425675 22 9 55 55 CD 10_1101-2021_01_07_425675 22 10 has have VBZ 10_1101-2021_01_07_425675 22 11 a a DT 10_1101-2021_01_07_425675 22 12 long long JJ 10_1101-2021_01_07_425675 22 13 way way NN 10_1101-2021_01_07_425675 22 14 to to TO 10_1101-2021_01_07_425675 22 15 go go VB 10_1101-2021_01_07_425675 22 16 towards towards IN 10_1101-2021_01_07_425675 22 17 this this DT 10_1101-2021_01_07_425675 22 18 goal goal NN 10_1101-2021_01_07_425675 22 19 , , , 10_1101-2021_01_07_425675 22 20 owing owe VBG 10_1101-2021_01_07_425675 22 21 to to IN 10_1101-2021_01_07_425675 22 22 limitations limitation NNS 10_1101-2021_01_07_425675 22 23 in in IN 10_1101-2021_01_07_425675 22 24 sample sample NN 10_1101-2021_01_07_425675 22 25 requirements requirement NNS 10_1101-2021_01_07_425675 22 26 , , , 10_1101-2021_01_07_425675 22 27 sequencing sequence VBG 10_1101-2021_01_07_425675 22 28 56 56 CD 10_1101-2021_01_07_425675 22 29 accuracy accuracy NN 10_1101-2021_01_07_425675 22 30 , , , 10_1101-2021_01_07_425675 22 31 read read VB 10_1101-2021_01_07_425675 22 32 length length NN 10_1101-2021_01_07_425675 22 33 and and CC 10_1101-2021_01_07_425675 22 34 sequence sequence NN 10_1101-2021_01_07_425675 22 35 assembly assembly NN 10_1101-2021_01_07_425675 22 36 , , , 10_1101-2021_01_07_425675 22 37 MS MS NNP 10_1101-2021_01_07_425675 22 38 has have VBZ 10_1101-2021_01_07_425675 22 39 been be VBN 10_1101-2021_01_07_425675 22 40 successfully successfully RB 10_1101-2021_01_07_425675 22 41 used use VBN 10_1101-2021_01_07_425675 22 42 to to TO 10_1101-2021_01_07_425675 22 43 profile profile VB 10_1101-2021_01_07_425675 22 44 the the DT 10_1101-2021_01_07_425675 22 45 57 57 CD 10_1101-2021_01_07_425675 22 46 antibody antibody NN 10_1101-2021_01_07_425675 22 47 repertoire repertoire NN 10_1101-2021_01_07_425675 22 48 and and CC 10_1101-2021_01_07_425675 22 49 obtain obtain VB 10_1101-2021_01_07_425675 22 50 ( ( -LRB- 10_1101-2021_01_07_425675 22 51 partial partial JJ 10_1101-2021_01_07_425675 22 52 ) ) -RRB- 10_1101-2021_01_07_425675 22 53 antibody antibody NN 10_1101-2021_01_07_425675 22 54 sequences sequence NNS 10_1101-2021_01_07_425675 22 55 beyond beyond IN 10_1101-2021_01_07_425675 22 56 those those DT 10_1101-2021_01_07_425675 22 57 available available JJ 10_1101-2021_01_07_425675 22 58 from from IN 10_1101-2021_01_07_425675 22 59 58 58 CD 10_1101-2021_01_07_425675 22 60 conventional conventional JJ 10_1101-2021_01_07_425675 22 61 sequencing sequencing NN 10_1101-2021_01_07_425675 22 62 strategies strategy NNS 10_1101-2021_01_07_425675 22 63 based base VBN 10_1101-2021_01_07_425675 22 64 on on IN 10_1101-2021_01_07_425675 22 65 cloning clone VBG 10_1101-2021_01_07_425675 22 66 / / SYM 10_1101-2021_01_07_425675 22 67 sequencing sequencing NN 10_1101-2021_01_07_425675 22 68 of of IN 10_1101-2021_01_07_425675 22 69 the the DT 10_1101-2021_01_07_425675 22 70 coding coding JJ 10_1101-2021_01_07_425675 22 71 mRNAs mrnas $ 10_1101-2021_01_07_425675 22 72 10 10 CD 10_1101-2021_01_07_425675 22 73 - - SYM 10_1101-2021_01_07_425675 22 74 17 17 CD 10_1101-2021_01_07_425675 22 75 . . . 10_1101-2021_01_07_425675 23 1 59 59 CD 10_1101-2021_01_07_425675 23 2 Most Most JJS 10_1101-2021_01_07_425675 23 3 MS MS NNP 10_1101-2021_01_07_425675 23 4 - - HYPH 10_1101-2021_01_07_425675 23 5 based base VBN 10_1101-2021_01_07_425675 23 6 strategies strategy NNS 10_1101-2021_01_07_425675 23 7 for for IN 10_1101-2021_01_07_425675 23 8 antibody antibody NN 10_1101-2021_01_07_425675 23 9 sequencing sequencing NN 10_1101-2021_01_07_425675 23 10 rely rely VB 10_1101-2021_01_07_425675 23 11 on on IN 10_1101-2021_01_07_425675 23 12 a a DT 10_1101-2021_01_07_425675 23 13 proteomics proteomic NNS 10_1101-2021_01_07_425675 23 14 - - HYPH 10_1101-2021_01_07_425675 23 15 type type NN 10_1101-2021_01_07_425675 23 16 bottom bottom NN 10_1101-2021_01_07_425675 23 17 - - HYPH 10_1101-2021_01_07_425675 23 18 up up RP 10_1101-2021_01_07_425675 23 19 LC-60 LC-60 NNP 10_1101-2021_01_07_425675 23 20 MS MS NNP 10_1101-2021_01_07_425675 23 21 / / SYM 10_1101-2021_01_07_425675 23 22 MS MS NNP 10_1101-2021_01_07_425675 23 23 workflow workflow NN 10_1101-2021_01_07_425675 23 24 , , , 10_1101-2021_01_07_425675 23 25 in in IN 10_1101-2021_01_07_425675 23 26 which which WDT 10_1101-2021_01_07_425675 23 27 the the DT 10_1101-2021_01_07_425675 23 28 antibody antibody NN 10_1101-2021_01_07_425675 23 29 product product NN 10_1101-2021_01_07_425675 23 30 is be VBZ 10_1101-2021_01_07_425675 23 31 digested digest VBN 10_1101-2021_01_07_425675 23 32 into into IN 10_1101-2021_01_07_425675 23 33 smaller small JJR 10_1101-2021_01_07_425675 23 34 peptides peptide NNS 10_1101-2021_01_07_425675 23 35 for for IN 10_1101-2021_01_07_425675 23 36 MS MS NNP 10_1101-2021_01_07_425675 23 37 analysis analysis NN 10_1101-2021_01_07_425675 23 38 61 61 CD 10_1101-2021_01_07_425675 23 39 14 14 CD 10_1101-2021_01_07_425675 23 40 , , , 10_1101-2021_01_07_425675 23 41 18 18 CD 10_1101-2021_01_07_425675 23 42 - - SYM 10_1101-2021_01_07_425675 23 43 23 23 CD 10_1101-2021_01_07_425675 23 44 . . . 10_1101-2021_01_07_425675 24 1 Available available JJ 10_1101-2021_01_07_425675 24 2 germline germline NN 10_1101-2021_01_07_425675 24 3 antibody antibody NN 10_1101-2021_01_07_425675 24 4 sequences sequence NNS 10_1101-2021_01_07_425675 24 5 are be VBP 10_1101-2021_01_07_425675 24 6 then then RB 10_1101-2021_01_07_425675 24 7 often often RB 10_1101-2021_01_07_425675 24 8 used use VBN 10_1101-2021_01_07_425675 24 9 either either CC 10_1101-2021_01_07_425675 24 10 as as IN 10_1101-2021_01_07_425675 24 11 a a DT 10_1101-2021_01_07_425675 24 12 template template NN 10_1101-2021_01_07_425675 24 13 to to TO 10_1101-2021_01_07_425675 24 14 guide guide VB 10_1101-2021_01_07_425675 24 15 62 62 CD 10_1101-2021_01_07_425675 24 16 .CC .CC , 10_1101-2021_01_07_425675 24 17 - - : 10_1101-2021_01_07_425675 24 18 BY by IN 10_1101-2021_01_07_425675 24 19 4.0 4.0 CD 10_1101-2021_01_07_425675 24 20 International International NNP 10_1101-2021_01_07_425675 24 21 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 24 22 under under IN 10_1101-2021_01_07_425675 24 23 a a DT 10_1101-2021_01_07_425675 24 24 ( ( -LRB- 10_1101-2021_01_07_425675 24 25 which which WDT 10_1101-2021_01_07_425675 24 26 was be VBD 10_1101-2021_01_07_425675 24 27 not not RB 10_1101-2021_01_07_425675 24 28 certified certify VBN 10_1101-2021_01_07_425675 24 29 by by IN 10_1101-2021_01_07_425675 24 30 peer peer NN 10_1101-2021_01_07_425675 24 31 review review NN 10_1101-2021_01_07_425675 24 32 ) ) -RRB- 10_1101-2021_01_07_425675 24 33 is be VBZ 10_1101-2021_01_07_425675 24 34 the the DT 10_1101-2021_01_07_425675 24 35 author author NN 10_1101-2021_01_07_425675 24 36 / / SYM 10_1101-2021_01_07_425675 24 37 funder funder NN 10_1101-2021_01_07_425675 24 38 , , , 10_1101-2021_01_07_425675 24 39 who who WP 10_1101-2021_01_07_425675 24 40 has have VBZ 10_1101-2021_01_07_425675 24 41 granted grant VBN 10_1101-2021_01_07_425675 24 42 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 24 43 a a DT 10_1101-2021_01_07_425675 24 44 license license NN 10_1101-2021_01_07_425675 24 45 to to TO 10_1101-2021_01_07_425675 24 46 display display VB 10_1101-2021_01_07_425675 24 47 the the DT 10_1101-2021_01_07_425675 24 48 preprint preprint NN 10_1101-2021_01_07_425675 24 49 in in IN 10_1101-2021_01_07_425675 24 50 perpetuity perpetuity NN 10_1101-2021_01_07_425675 24 51 . . . 10_1101-2021_01_07_425675 25 1 It -PRON- PRP 10_1101-2021_01_07_425675 25 2 is be VBZ 10_1101-2021_01_07_425675 25 3 made make VBN 10_1101-2021_01_07_425675 25 4 The the DT 10_1101-2021_01_07_425675 25 5 copyright copyright NN 10_1101-2021_01_07_425675 25 6 holder holder NN 10_1101-2021_01_07_425675 25 7 for for IN 10_1101-2021_01_07_425675 25 8 this this DT 10_1101-2021_01_07_425675 25 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 25 10 version version NN 10_1101-2021_01_07_425675 25 11 posted post VBD 10_1101-2021_01_07_425675 25 12 January January NNP 10_1101-2021_01_07_425675 25 13 8 8 CD 10_1101-2021_01_07_425675 25 14 , , , 10_1101-2021_01_07_425675 25 15 2021 2021 CD 10_1101-2021_01_07_425675 25 16 . . . 10_1101-2021_01_07_425675 25 17 ; ; : 10_1101-2021_01_07_425675 25 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 25 19 : : : 10_1101-2021_01_07_425675 25 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 25 21 preprint preprint NN 10_1101-2021_01_07_425675 25 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 25 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 25 24 4 4 CD 10_1101-2021_01_07_425675 25 25 assembly assembly NN 10_1101-2021_01_07_425675 25 26 of of IN 10_1101-2021_01_07_425675 25 27 de de FW 10_1101-2021_01_07_425675 25 28 novo novo NNP 10_1101-2021_01_07_425675 25 29 peptide peptide NNP 10_1101-2021_01_07_425675 25 30 reads read VBZ 10_1101-2021_01_07_425675 25 31 ( ( -LRB- 10_1101-2021_01_07_425675 25 32 such such JJ 10_1101-2021_01_07_425675 25 33 as as IN 10_1101-2021_01_07_425675 25 34 in in IN 10_1101-2021_01_07_425675 25 35 PEAKS PEAKS NNP 10_1101-2021_01_07_425675 25 36 Ab Ab NNP 10_1101-2021_01_07_425675 25 37 ) ) -RRB- 10_1101-2021_01_07_425675 25 38 23 23 CD 10_1101-2021_01_07_425675 25 39 , , , 10_1101-2021_01_07_425675 25 40 or or CC 10_1101-2021_01_07_425675 25 41 used use VBN 10_1101-2021_01_07_425675 25 42 as as IN 10_1101-2021_01_07_425675 25 43 a a DT 10_1101-2021_01_07_425675 25 44 starting starting NN 10_1101-2021_01_07_425675 25 45 point point NN 10_1101-2021_01_07_425675 25 46 to to IN 10_1101-2021_01_07_425675 25 47 63 63 CD 10_1101-2021_01_07_425675 25 48 iteratively iteratively RB 10_1101-2021_01_07_425675 25 49 identify identify VBP 10_1101-2021_01_07_425675 25 50 somatic somatic JJ 10_1101-2021_01_07_425675 25 51 mutations mutation NNS 10_1101-2021_01_07_425675 25 52 to to TO 10_1101-2021_01_07_425675 25 53 arrive arrive VB 10_1101-2021_01_07_425675 25 54 at at IN 10_1101-2021_01_07_425675 25 55 the the DT 10_1101-2021_01_07_425675 25 56 mature mature JJ 10_1101-2021_01_07_425675 25 57 antibody antibody NN 10_1101-2021_01_07_425675 25 58 sequence sequence NN 10_1101-2021_01_07_425675 25 59 ( ( -LRB- 10_1101-2021_01_07_425675 25 60 such such JJ 10_1101-2021_01_07_425675 25 61 as as IN 10_1101-2021_01_07_425675 25 62 in in IN 10_1101-2021_01_07_425675 25 63 64 64 CD 10_1101-2021_01_07_425675 25 64 Supernovo Supernovo NNP 10_1101-2021_01_07_425675 25 65 ) ) -RRB- 10_1101-2021_01_07_425675 25 66 21 21 CD 10_1101-2021_01_07_425675 25 67 . . . 10_1101-2021_01_07_425675 26 1 To to TO 10_1101-2021_01_07_425675 26 2 maximize maximize VB 10_1101-2021_01_07_425675 26 3 sequence sequence NN 10_1101-2021_01_07_425675 26 4 coverage coverage NN 10_1101-2021_01_07_425675 26 5 and and CC 10_1101-2021_01_07_425675 26 6 aid aid NN 10_1101-2021_01_07_425675 26 7 read read VBD 10_1101-2021_01_07_425675 26 8 assembly assembly NNP 10_1101-2021_01_07_425675 26 9 , , , 10_1101-2021_01_07_425675 26 10 these these DT 10_1101-2021_01_07_425675 26 11 MS MS NNP 10_1101-2021_01_07_425675 26 12 - - HYPH 10_1101-2021_01_07_425675 26 13 based base VBN 10_1101-2021_01_07_425675 26 14 65 65 CD 10_1101-2021_01_07_425675 26 15 workflows workflow NNS 10_1101-2021_01_07_425675 26 16 typically typically RB 10_1101-2021_01_07_425675 26 17 use use VBP 10_1101-2021_01_07_425675 26 18 a a DT 10_1101-2021_01_07_425675 26 19 combination combination NN 10_1101-2021_01_07_425675 26 20 of of IN 10_1101-2021_01_07_425675 26 21 complementary complementary JJ 10_1101-2021_01_07_425675 26 22 proteases protease NNS 10_1101-2021_01_07_425675 26 23 and and CC 10_1101-2021_01_07_425675 26 24 aspecific aspecific JJ 10_1101-2021_01_07_425675 26 25 digestion digestion NN 10_1101-2021_01_07_425675 26 26 to to IN 10_1101-2021_01_07_425675 26 27 66 66 CD 10_1101-2021_01_07_425675 26 28 generate generate NN 10_1101-2021_01_07_425675 26 29 overlapping overlapping NN 10_1101-2021_01_07_425675 26 30 peptides peptide NNS 10_1101-2021_01_07_425675 26 31 . . . 10_1101-2021_01_07_425675 27 1 The the DT 10_1101-2021_01_07_425675 27 2 most most RBS 10_1101-2021_01_07_425675 27 3 straightforward straightforward JJ 10_1101-2021_01_07_425675 27 4 application application NN 10_1101-2021_01_07_425675 27 5 of of IN 10_1101-2021_01_07_425675 27 6 these these DT 10_1101-2021_01_07_425675 27 7 MS MS NNP 10_1101-2021_01_07_425675 27 8 - - HYPH 10_1101-2021_01_07_425675 27 9 based base VBN 10_1101-2021_01_07_425675 27 10 67 67 CD 10_1101-2021_01_07_425675 27 11 sequencing sequence VBG 10_1101-2021_01_07_425675 27 12 workflows workflow NNS 10_1101-2021_01_07_425675 27 13 is be VBZ 10_1101-2021_01_07_425675 27 14 the the DT 10_1101-2021_01_07_425675 27 15 successful successful JJ 10_1101-2021_01_07_425675 27 16 sequencing sequencing NN 10_1101-2021_01_07_425675 27 17 of of IN 10_1101-2021_01_07_425675 27 18 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 27 19 antibodies antibody NNS 10_1101-2021_01_07_425675 27 20 from from IN 10_1101-2021_01_07_425675 27 21 ( ( -LRB- 10_1101-2021_01_07_425675 27 22 lost lose VBN 10_1101-2021_01_07_425675 27 23 ) ) -RRB- 10_1101-2021_01_07_425675 27 24 68 68 CD 10_1101-2021_01_07_425675 27 25 hybridoma hybridoma NN 10_1101-2021_01_07_425675 27 26 cell cell NN 10_1101-2021_01_07_425675 27 27 lines line NNS 10_1101-2021_01_07_425675 27 28 , , , 10_1101-2021_01_07_425675 27 29 but but CC 10_1101-2021_01_07_425675 27 30 it -PRON- PRP 10_1101-2021_01_07_425675 27 31 also also RB 10_1101-2021_01_07_425675 27 32 forms form VBZ 10_1101-2021_01_07_425675 27 33 the the DT 10_1101-2021_01_07_425675 27 34 basis basis NN 10_1101-2021_01_07_425675 27 35 of of IN 10_1101-2021_01_07_425675 27 36 more more RBR 10_1101-2021_01_07_425675 27 37 advanced advanced JJ 10_1101-2021_01_07_425675 27 38 and and CC 10_1101-2021_01_07_425675 27 39 challenging challenging JJ 10_1101-2021_01_07_425675 27 40 applications application NNS 10_1101-2021_01_07_425675 27 41 to to IN 10_1101-2021_01_07_425675 27 42 69 69 CD 10_1101-2021_01_07_425675 27 43 characterize characterize VB 10_1101-2021_01_07_425675 27 44 polyclonal polyclonal JJ 10_1101-2021_01_07_425675 27 45 antibody antibody NN 10_1101-2021_01_07_425675 27 46 mixtures mixture NNS 10_1101-2021_01_07_425675 27 47 and and CC 10_1101-2021_01_07_425675 27 48 profile profile VB 10_1101-2021_01_07_425675 27 49 the the DT 10_1101-2021_01_07_425675 27 50 full full JJ 10_1101-2021_01_07_425675 27 51 antibody antibody NN 10_1101-2021_01_07_425675 27 52 repertoire repertoire NN 10_1101-2021_01_07_425675 27 53 from from IN 10_1101-2021_01_07_425675 27 54 serum serum NNP 10_1101-2021_01_07_425675 27 55 . . . 10_1101-2021_01_07_425675 28 1 70 70 CD 10_1101-2021_01_07_425675 28 2 Here here RB 10_1101-2021_01_07_425675 28 3 we -PRON- PRP 10_1101-2021_01_07_425675 28 4 describe describe VBP 10_1101-2021_01_07_425675 28 5 an an DT 10_1101-2021_01_07_425675 28 6 efficient efficient JJ 10_1101-2021_01_07_425675 28 7 protocol protocol NN 10_1101-2021_01_07_425675 28 8 for for IN 10_1101-2021_01_07_425675 28 9 MS MS NNP 10_1101-2021_01_07_425675 28 10 - - HYPH 10_1101-2021_01_07_425675 28 11 based base VBN 10_1101-2021_01_07_425675 28 12 sequencing sequencing NN 10_1101-2021_01_07_425675 28 13 of of IN 10_1101-2021_01_07_425675 28 14 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 28 15 antibodies antibody NNS 10_1101-2021_01_07_425675 28 16 . . . 10_1101-2021_01_07_425675 29 1 The the DT 10_1101-2021_01_07_425675 29 2 71 71 CD 10_1101-2021_01_07_425675 29 3 protocol protocol NN 10_1101-2021_01_07_425675 29 4 requires require VBZ 10_1101-2021_01_07_425675 29 5 approximately approximately RB 10_1101-2021_01_07_425675 29 6 200 200 CD 10_1101-2021_01_07_425675 29 7 picomol picomol NN 10_1101-2021_01_07_425675 29 8 of of IN 10_1101-2021_01_07_425675 29 9 the the DT 10_1101-2021_01_07_425675 29 10 antibody antibody NN 10_1101-2021_01_07_425675 29 11 product product NN 10_1101-2021_01_07_425675 29 12 and and CC 10_1101-2021_01_07_425675 29 13 sample sample NN 10_1101-2021_01_07_425675 29 14 preparation preparation NN 10_1101-2021_01_07_425675 29 15 can can MD 10_1101-2021_01_07_425675 29 16 72 72 CD 10_1101-2021_01_07_425675 29 17 be be VB 10_1101-2021_01_07_425675 29 18 completed complete VBN 10_1101-2021_01_07_425675 29 19 within within IN 10_1101-2021_01_07_425675 29 20 one one CD 10_1101-2021_01_07_425675 29 21 working work VBG 10_1101-2021_01_07_425675 29 22 day day NN 10_1101-2021_01_07_425675 29 23 . . . 10_1101-2021_01_07_425675 30 1 We -PRON- PRP 10_1101-2021_01_07_425675 30 2 selected select VBD 10_1101-2021_01_07_425675 30 3 a a DT 10_1101-2021_01_07_425675 30 4 panel panel NN 10_1101-2021_01_07_425675 30 5 of of IN 10_1101-2021_01_07_425675 30 6 9 9 CD 10_1101-2021_01_07_425675 30 7 proteases protease NNS 10_1101-2021_01_07_425675 30 8 with with IN 10_1101-2021_01_07_425675 30 9 complementary complementary JJ 10_1101-2021_01_07_425675 30 10 73 73 CD 10_1101-2021_01_07_425675 30 11 specificities specificity NNS 10_1101-2021_01_07_425675 30 12 , , , 10_1101-2021_01_07_425675 30 13 which which WDT 10_1101-2021_01_07_425675 30 14 are be VBP 10_1101-2021_01_07_425675 30 15 active active JJ 10_1101-2021_01_07_425675 30 16 in in IN 10_1101-2021_01_07_425675 30 17 the the DT 10_1101-2021_01_07_425675 30 18 same same JJ 10_1101-2021_01_07_425675 30 19 buffer buffer NN 10_1101-2021_01_07_425675 30 20 conditions condition NNS 10_1101-2021_01_07_425675 30 21 for for IN 10_1101-2021_01_07_425675 30 22 parallel parallel JJ 10_1101-2021_01_07_425675 30 23 digestion digestion NN 10_1101-2021_01_07_425675 30 24 of of IN 10_1101-2021_01_07_425675 30 25 the the DT 10_1101-2021_01_07_425675 30 26 antibodies antibody NNS 10_1101-2021_01_07_425675 30 27 . . . 10_1101-2021_01_07_425675 31 1 74 74 CD 10_1101-2021_01_07_425675 31 2 We -PRON- PRP 10_1101-2021_01_07_425675 31 3 developed develop VBD 10_1101-2021_01_07_425675 31 4 a a DT 10_1101-2021_01_07_425675 31 5 dual dual JJ 10_1101-2021_01_07_425675 31 6 fragmentation fragmentation NN 10_1101-2021_01_07_425675 31 7 strategy strategy NN 10_1101-2021_01_07_425675 31 8 for for IN 10_1101-2021_01_07_425675 31 9 MS MS NNP 10_1101-2021_01_07_425675 31 10 / / SYM 10_1101-2021_01_07_425675 31 11 MS MS NNP 10_1101-2021_01_07_425675 31 12 analysis analysis NN 10_1101-2021_01_07_425675 31 13 of of IN 10_1101-2021_01_07_425675 31 14 the the DT 10_1101-2021_01_07_425675 31 15 resulting result VBG 10_1101-2021_01_07_425675 31 16 peptides peptide NNS 10_1101-2021_01_07_425675 31 17 to to TO 10_1101-2021_01_07_425675 31 18 yield yield VB 10_1101-2021_01_07_425675 31 19 75 75 CD 10_1101-2021_01_07_425675 31 20 rich rich JJ 10_1101-2021_01_07_425675 31 21 sequence sequence NN 10_1101-2021_01_07_425675 31 22 information information NN 10_1101-2021_01_07_425675 31 23 from from IN 10_1101-2021_01_07_425675 31 24 the the DT 10_1101-2021_01_07_425675 31 25 fragmentation fragmentation NN 10_1101-2021_01_07_425675 31 26 spectra spectra NN 10_1101-2021_01_07_425675 31 27 of of IN 10_1101-2021_01_07_425675 31 28 the the DT 10_1101-2021_01_07_425675 31 29 peptides peptide NNS 10_1101-2021_01_07_425675 31 30 . . . 10_1101-2021_01_07_425675 32 1 The the DT 10_1101-2021_01_07_425675 32 2 protocol protocol NN 10_1101-2021_01_07_425675 32 3 yields yield VBZ 10_1101-2021_01_07_425675 32 4 full full JJ 10_1101-2021_01_07_425675 32 5 76 76 CD 10_1101-2021_01_07_425675 32 6 and and CC 10_1101-2021_01_07_425675 32 7 deep deep JJ 10_1101-2021_01_07_425675 32 8 sequence sequence NN 10_1101-2021_01_07_425675 32 9 coverage coverage NN 10_1101-2021_01_07_425675 32 10 of of IN 10_1101-2021_01_07_425675 32 11 the the DT 10_1101-2021_01_07_425675 32 12 variable variable JJ 10_1101-2021_01_07_425675 32 13 domains domain NNS 10_1101-2021_01_07_425675 32 14 of of IN 10_1101-2021_01_07_425675 32 15 both both CC 10_1101-2021_01_07_425675 32 16 heavy heavy JJ 10_1101-2021_01_07_425675 32 17 and and CC 10_1101-2021_01_07_425675 32 18 light light JJ 10_1101-2021_01_07_425675 32 19 chains chain NNS 10_1101-2021_01_07_425675 32 20 as as IN 10_1101-2021_01_07_425675 32 21 77 77 CD 10_1101-2021_01_07_425675 32 22 demonstrated demonstrate VBD 10_1101-2021_01_07_425675 32 23 on on IN 10_1101-2021_01_07_425675 32 24 the the DT 10_1101-2021_01_07_425675 32 25 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 32 26 antibody antibody NN 10_1101-2021_01_07_425675 32 27 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 32 28 . . . 10_1101-2021_01_07_425675 33 1 As as IN 10_1101-2021_01_07_425675 33 2 a a DT 10_1101-2021_01_07_425675 33 3 test test NN 10_1101-2021_01_07_425675 33 4 case case NN 10_1101-2021_01_07_425675 33 5 , , , 10_1101-2021_01_07_425675 33 6 we -PRON- PRP 10_1101-2021_01_07_425675 33 7 used use VBD 10_1101-2021_01_07_425675 33 8 our -PRON- PRP$ 10_1101-2021_01_07_425675 33 9 protocol protocol NN 10_1101-2021_01_07_425675 33 10 to to IN 10_1101-2021_01_07_425675 33 11 78 78 CD 10_1101-2021_01_07_425675 33 12 sequence sequence NN 10_1101-2021_01_07_425675 33 13 the the DT 10_1101-2021_01_07_425675 33 14 widely widely RB 10_1101-2021_01_07_425675 33 15 used use VBN 10_1101-2021_01_07_425675 33 16 anti anti JJ 10_1101-2021_01_07_425675 33 17 - - JJ 10_1101-2021_01_07_425675 33 18 FLAG FLAG NNP 10_1101-2021_01_07_425675 33 19 - - HYPH 10_1101-2021_01_07_425675 33 20 M2 M2 NNP 10_1101-2021_01_07_425675 33 21 mouse mouse NNP 10_1101-2021_01_07_425675 33 22 monoclonal monoclonal NNP 10_1101-2021_01_07_425675 33 23 antibody antibody NN 10_1101-2021_01_07_425675 33 24 , , , 10_1101-2021_01_07_425675 33 25 for for IN 10_1101-2021_01_07_425675 33 26 which which WDT 10_1101-2021_01_07_425675 33 27 no no DT 10_1101-2021_01_07_425675 33 28 sequence sequence NN 10_1101-2021_01_07_425675 33 29 79 79 CD 10_1101-2021_01_07_425675 33 30 was be VBD 10_1101-2021_01_07_425675 33 31 publicly publicly RB 10_1101-2021_01_07_425675 33 32 available available JJ 10_1101-2021_01_07_425675 33 33 despite despite IN 10_1101-2021_01_07_425675 33 34 its -PRON- PRP$ 10_1101-2021_01_07_425675 33 35 described described JJ 10_1101-2021_01_07_425675 33 36 use use NN 10_1101-2021_01_07_425675 33 37 in in IN 10_1101-2021_01_07_425675 33 38 5000 5000 CD 10_1101-2021_01_07_425675 33 39 + + SYM 10_1101-2021_01_07_425675 33 40 peer peer NN 10_1101-2021_01_07_425675 33 41 - - HYPH 10_1101-2021_01_07_425675 33 42 reviewed review VBN 10_1101-2021_01_07_425675 33 43 publications publication NNS 10_1101-2021_01_07_425675 33 44 24 24 CD 10_1101-2021_01_07_425675 33 45 - - SYM 10_1101-2021_01_07_425675 33 46 25 25 CD 10_1101-2021_01_07_425675 33 47 . . . 10_1101-2021_01_07_425675 34 1 The the DT 10_1101-2021_01_07_425675 34 2 80 80 CD 10_1101-2021_01_07_425675 34 3 protocol protocol NN 10_1101-2021_01_07_425675 34 4 achieved achieve VBD 10_1101-2021_01_07_425675 34 5 full full JJ 10_1101-2021_01_07_425675 34 6 sequence sequence NN 10_1101-2021_01_07_425675 34 7 coverage coverage NN 10_1101-2021_01_07_425675 34 8 of of IN 10_1101-2021_01_07_425675 34 9 the the DT 10_1101-2021_01_07_425675 34 10 variable variable JJ 10_1101-2021_01_07_425675 34 11 domains domain NNS 10_1101-2021_01_07_425675 34 12 of of IN 10_1101-2021_01_07_425675 34 13 both both CC 10_1101-2021_01_07_425675 34 14 heavy heavy JJ 10_1101-2021_01_07_425675 34 15 and and CC 10_1101-2021_01_07_425675 34 16 light light JJ 10_1101-2021_01_07_425675 34 17 chains chain NNS 10_1101-2021_01_07_425675 34 18 , , , 10_1101-2021_01_07_425675 34 19 81 81 CD 10_1101-2021_01_07_425675 34 20 including include VBG 10_1101-2021_01_07_425675 34 21 all all DT 10_1101-2021_01_07_425675 34 22 complementarity complementarity NN 10_1101-2021_01_07_425675 34 23 determining determine VBG 10_1101-2021_01_07_425675 34 24 regions region NNS 10_1101-2021_01_07_425675 34 25 ( ( -LRB- 10_1101-2021_01_07_425675 34 26 CDRs CDRs NNP 10_1101-2021_01_07_425675 34 27 ) ) -RRB- 10_1101-2021_01_07_425675 34 28 . . . 10_1101-2021_01_07_425675 35 1 The the DT 10_1101-2021_01_07_425675 35 2 obtained obtain VBN 10_1101-2021_01_07_425675 35 3 sequence sequence NN 10_1101-2021_01_07_425675 35 4 was be VBD 10_1101-2021_01_07_425675 35 5 82 82 CD 10_1101-2021_01_07_425675 35 6 successfully successfully RB 10_1101-2021_01_07_425675 35 7 validated validate VBN 10_1101-2021_01_07_425675 35 8 by by IN 10_1101-2021_01_07_425675 35 9 remodeling remodel VBG 10_1101-2021_01_07_425675 35 10 the the DT 10_1101-2021_01_07_425675 35 11 published publish VBN 10_1101-2021_01_07_425675 35 12 crystal crystal NN 10_1101-2021_01_07_425675 35 13 structure structure NN 10_1101-2021_01_07_425675 35 14 of of IN 10_1101-2021_01_07_425675 35 15 the the DT 10_1101-2021_01_07_425675 35 16 anti anti JJ 10_1101-2021_01_07_425675 35 17 - - JJ 10_1101-2021_01_07_425675 35 18 FLAG FLAG NNP 10_1101-2021_01_07_425675 35 19 - - HYPH 10_1101-2021_01_07_425675 35 20 M2 M2 NNP 10_1101-2021_01_07_425675 35 21 Fab Fab NNP 10_1101-2021_01_07_425675 35 22 and and CC 10_1101-2021_01_07_425675 35 23 83 83 CD 10_1101-2021_01_07_425675 35 24 demonstrating demonstrating NN 10_1101-2021_01_07_425675 35 25 binding binding NN 10_1101-2021_01_07_425675 35 26 of of IN 10_1101-2021_01_07_425675 35 27 the the DT 10_1101-2021_01_07_425675 35 28 synthetic synthetic JJ 10_1101-2021_01_07_425675 35 29 recombinant recombinant JJ 10_1101-2021_01_07_425675 35 30 antibody antibody NN 10_1101-2021_01_07_425675 35 31 following follow VBG 10_1101-2021_01_07_425675 35 32 the the DT 10_1101-2021_01_07_425675 35 33 experimental experimental JJ 10_1101-2021_01_07_425675 35 34 sequence sequence NN 10_1101-2021_01_07_425675 35 35 84 84 CD 10_1101-2021_01_07_425675 35 36 to to IN 10_1101-2021_01_07_425675 35 37 a a DT 10_1101-2021_01_07_425675 35 38 FLAG FLAG NNP 10_1101-2021_01_07_425675 35 39 - - HYPH 10_1101-2021_01_07_425675 35 40 tagged tag VBN 10_1101-2021_01_07_425675 35 41 protein protein NN 10_1101-2021_01_07_425675 35 42 in in IN 10_1101-2021_01_07_425675 35 43 Western western JJ 10_1101-2021_01_07_425675 35 44 blot blot NN 10_1101-2021_01_07_425675 35 45 analysis analysis NN 10_1101-2021_01_07_425675 35 46 . . . 10_1101-2021_01_07_425675 36 1 The the DT 10_1101-2021_01_07_425675 36 2 protocol protocol NN 10_1101-2021_01_07_425675 36 3 developed develop VBN 10_1101-2021_01_07_425675 36 4 here here RB 10_1101-2021_01_07_425675 36 5 thus thus RB 10_1101-2021_01_07_425675 36 6 offers offer VBZ 10_1101-2021_01_07_425675 36 7 robust robust JJ 10_1101-2021_01_07_425675 36 8 85 85 CD 10_1101-2021_01_07_425675 36 9 and and CC 10_1101-2021_01_07_425675 36 10 reliable reliable JJ 10_1101-2021_01_07_425675 36 11 sequencing sequencing NN 10_1101-2021_01_07_425675 36 12 of of IN 10_1101-2021_01_07_425675 36 13 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 36 14 antibodies antibody NNS 10_1101-2021_01_07_425675 36 15 with with IN 10_1101-2021_01_07_425675 36 16 prospective prospective JJ 10_1101-2021_01_07_425675 36 17 applications application NNS 10_1101-2021_01_07_425675 36 18 for for IN 10_1101-2021_01_07_425675 36 19 sequencing sequence VBG 10_1101-2021_01_07_425675 36 20 86 86 CD 10_1101-2021_01_07_425675 36 21 secreted secrete VBN 10_1101-2021_01_07_425675 36 22 antibodies antibody NNS 10_1101-2021_01_07_425675 36 23 from from IN 10_1101-2021_01_07_425675 36 24 bodily bodily NNP 10_1101-2021_01_07_425675 36 25 fluids fluid NNS 10_1101-2021_01_07_425675 36 26 . . . 10_1101-2021_01_07_425675 37 1 87 87 CD 10_1101-2021_01_07_425675 37 2 88 88 CD 10_1101-2021_01_07_425675 37 3 Results result NNS 10_1101-2021_01_07_425675 37 4 89 89 CD 10_1101-2021_01_07_425675 37 5 We -PRON- PRP 10_1101-2021_01_07_425675 37 6 used use VBD 10_1101-2021_01_07_425675 37 7 an an DT 10_1101-2021_01_07_425675 37 8 in in IN 10_1101-2021_01_07_425675 37 9 - - HYPH 10_1101-2021_01_07_425675 37 10 solution solution NN 10_1101-2021_01_07_425675 37 11 digestion digestion NN 10_1101-2021_01_07_425675 37 12 protocol protocol NN 10_1101-2021_01_07_425675 37 13 , , , 10_1101-2021_01_07_425675 37 14 with with IN 10_1101-2021_01_07_425675 37 15 sodium sodium NN 10_1101-2021_01_07_425675 37 16 - - HYPH 10_1101-2021_01_07_425675 37 17 deoxycholate deoxycholate NN 10_1101-2021_01_07_425675 37 18 as as IN 10_1101-2021_01_07_425675 37 19 the the DT 10_1101-2021_01_07_425675 37 20 denaturing denature VBG 10_1101-2021_01_07_425675 37 21 agent agent NN 10_1101-2021_01_07_425675 37 22 , , , 10_1101-2021_01_07_425675 37 23 to to IN 10_1101-2021_01_07_425675 37 24 90 90 CD 10_1101-2021_01_07_425675 37 25 generate generate NN 10_1101-2021_01_07_425675 37 26 peptides peptide NNS 10_1101-2021_01_07_425675 37 27 from from IN 10_1101-2021_01_07_425675 37 28 the the DT 10_1101-2021_01_07_425675 37 29 antibodies antibody NNS 10_1101-2021_01_07_425675 37 30 for for IN 10_1101-2021_01_07_425675 37 31 LC LC NNP 10_1101-2021_01_07_425675 37 32 - - HYPH 10_1101-2021_01_07_425675 37 33 MS MS NNP 10_1101-2021_01_07_425675 37 34 / / SYM 10_1101-2021_01_07_425675 37 35 MS MS NNP 10_1101-2021_01_07_425675 37 36 analysis analysis NN 10_1101-2021_01_07_425675 37 37 . . . 10_1101-2021_01_07_425675 38 1 Following follow VBG 10_1101-2021_01_07_425675 38 2 heat heat NN 10_1101-2021_01_07_425675 38 3 denaturation denaturation NN 10_1101-2021_01_07_425675 38 4 and and CC 10_1101-2021_01_07_425675 38 5 91 91 CD 10_1101-2021_01_07_425675 38 6 disulfide disulfide JJ 10_1101-2021_01_07_425675 38 7 bond bond NN 10_1101-2021_01_07_425675 38 8 reduction reduction NN 10_1101-2021_01_07_425675 38 9 , , , 10_1101-2021_01_07_425675 38 10 we -PRON- PRP 10_1101-2021_01_07_425675 38 11 used use VBD 10_1101-2021_01_07_425675 38 12 iodoacetic iodoacetic JJ 10_1101-2021_01_07_425675 38 13 acid acid NN 10_1101-2021_01_07_425675 38 14 as as IN 10_1101-2021_01_07_425675 38 15 the the DT 10_1101-2021_01_07_425675 38 16 alkylating alkylate VBG 10_1101-2021_01_07_425675 38 17 agent agent NN 10_1101-2021_01_07_425675 38 18 to to TO 10_1101-2021_01_07_425675 38 19 cap cap VB 10_1101-2021_01_07_425675 38 20 free free JJ 10_1101-2021_01_07_425675 38 21 cysteines cysteine NNS 10_1101-2021_01_07_425675 38 22 . . . 10_1101-2021_01_07_425675 39 1 92 92 CD 10_1101-2021_01_07_425675 39 2 Note note NN 10_1101-2021_01_07_425675 39 3 that that IN 10_1101-2021_01_07_425675 39 4 conventional conventional JJ 10_1101-2021_01_07_425675 39 5 alkylating alkylating NN 10_1101-2021_01_07_425675 39 6 agents agent NNS 10_1101-2021_01_07_425675 39 7 like like IN 10_1101-2021_01_07_425675 39 8 iodo-/chloroacetamide iodo-/chloroacetamide JJ 10_1101-2021_01_07_425675 39 9 generate generate NN 10_1101-2021_01_07_425675 39 10 +57 +57 CD 10_1101-2021_01_07_425675 39 11 Da Da NNP 10_1101-2021_01_07_425675 39 12 mass mass NN 10_1101-2021_01_07_425675 39 13 93 93 CD 10_1101-2021_01_07_425675 39 14 differences difference NNS 10_1101-2021_01_07_425675 39 15 on on IN 10_1101-2021_01_07_425675 39 16 cysteines cysteine NNS 10_1101-2021_01_07_425675 39 17 and and CC 10_1101-2021_01_07_425675 39 18 primary primary JJ 10_1101-2021_01_07_425675 39 19 amines amine NNS 10_1101-2021_01_07_425675 39 20 , , , 10_1101-2021_01_07_425675 39 21 which which WDT 10_1101-2021_01_07_425675 39 22 may may MD 10_1101-2021_01_07_425675 39 23 lead lead VB 10_1101-2021_01_07_425675 39 24 to to IN 10_1101-2021_01_07_425675 39 25 spurious spurious JJ 10_1101-2021_01_07_425675 39 26 assignments assignment NNS 10_1101-2021_01_07_425675 39 27 as as IN 10_1101-2021_01_07_425675 39 28 glycine glycine NN 10_1101-2021_01_07_425675 39 29 94 94 CD 10_1101-2021_01_07_425675 39 30 .CC .CC , 10_1101-2021_01_07_425675 39 31 - - : 10_1101-2021_01_07_425675 39 32 BY by IN 10_1101-2021_01_07_425675 39 33 4.0 4.0 CD 10_1101-2021_01_07_425675 39 34 International International NNP 10_1101-2021_01_07_425675 39 35 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 39 36 under under IN 10_1101-2021_01_07_425675 39 37 a a DT 10_1101-2021_01_07_425675 39 38 ( ( -LRB- 10_1101-2021_01_07_425675 39 39 which which WDT 10_1101-2021_01_07_425675 39 40 was be VBD 10_1101-2021_01_07_425675 39 41 not not RB 10_1101-2021_01_07_425675 39 42 certified certify VBN 10_1101-2021_01_07_425675 39 43 by by IN 10_1101-2021_01_07_425675 39 44 peer peer NN 10_1101-2021_01_07_425675 39 45 review review NN 10_1101-2021_01_07_425675 39 46 ) ) -RRB- 10_1101-2021_01_07_425675 39 47 is be VBZ 10_1101-2021_01_07_425675 39 48 the the DT 10_1101-2021_01_07_425675 39 49 author author NN 10_1101-2021_01_07_425675 39 50 / / SYM 10_1101-2021_01_07_425675 39 51 funder funder NN 10_1101-2021_01_07_425675 39 52 , , , 10_1101-2021_01_07_425675 39 53 who who WP 10_1101-2021_01_07_425675 39 54 has have VBZ 10_1101-2021_01_07_425675 39 55 granted grant VBN 10_1101-2021_01_07_425675 39 56 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 39 57 a a DT 10_1101-2021_01_07_425675 39 58 license license NN 10_1101-2021_01_07_425675 39 59 to to TO 10_1101-2021_01_07_425675 39 60 display display VB 10_1101-2021_01_07_425675 39 61 the the DT 10_1101-2021_01_07_425675 39 62 preprint preprint NN 10_1101-2021_01_07_425675 39 63 in in IN 10_1101-2021_01_07_425675 39 64 perpetuity perpetuity NN 10_1101-2021_01_07_425675 39 65 . . . 10_1101-2021_01_07_425675 40 1 It -PRON- PRP 10_1101-2021_01_07_425675 40 2 is be VBZ 10_1101-2021_01_07_425675 40 3 made make VBN 10_1101-2021_01_07_425675 40 4 The the DT 10_1101-2021_01_07_425675 40 5 copyright copyright NN 10_1101-2021_01_07_425675 40 6 holder holder NN 10_1101-2021_01_07_425675 40 7 for for IN 10_1101-2021_01_07_425675 40 8 this this DT 10_1101-2021_01_07_425675 40 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 40 10 version version NN 10_1101-2021_01_07_425675 40 11 posted post VBD 10_1101-2021_01_07_425675 40 12 January January NNP 10_1101-2021_01_07_425675 40 13 8 8 CD 10_1101-2021_01_07_425675 40 14 , , , 10_1101-2021_01_07_425675 40 15 2021 2021 CD 10_1101-2021_01_07_425675 40 16 . . . 10_1101-2021_01_07_425675 40 17 ; ; : 10_1101-2021_01_07_425675 40 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 40 19 : : : 10_1101-2021_01_07_425675 40 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 40 21 preprint preprint NN 10_1101-2021_01_07_425675 40 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 40 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 40 24 5 5 CD 10_1101-2021_01_07_425675 40 25 residues residue NNS 10_1101-2021_01_07_425675 40 26 in in IN 10_1101-2021_01_07_425675 40 27 de de NNP 10_1101-2021_01_07_425675 40 28 novo novo NNP 10_1101-2021_01_07_425675 40 29 sequencing sequencing NN 10_1101-2021_01_07_425675 40 30 . . . 10_1101-2021_01_07_425675 41 1 The the DT 10_1101-2021_01_07_425675 41 2 +58 +58 CD 10_1101-2021_01_07_425675 41 3 Da Da NNP 10_1101-2021_01_07_425675 41 4 mass mass NN 10_1101-2021_01_07_425675 41 5 differences difference NNS 10_1101-2021_01_07_425675 41 6 generated generate VBN 10_1101-2021_01_07_425675 41 7 by by IN 10_1101-2021_01_07_425675 41 8 alkylation alkylation NN 10_1101-2021_01_07_425675 41 9 with with IN 10_1101-2021_01_07_425675 41 10 95 95 CD 10_1101-2021_01_07_425675 41 11 iodoacetic iodoacetic JJ 10_1101-2021_01_07_425675 41 12 acid acid NN 10_1101-2021_01_07_425675 41 13 circumvents circumvent VBZ 10_1101-2021_01_07_425675 41 14 this this DT 10_1101-2021_01_07_425675 41 15 potential potential JJ 10_1101-2021_01_07_425675 41 16 pitfall pitfall NN 10_1101-2021_01_07_425675 41 17 . . . 10_1101-2021_01_07_425675 42 1 96 96 CD 10_1101-2021_01_07_425675 42 2 We -PRON- PRP 10_1101-2021_01_07_425675 42 3 chose choose VBD 10_1101-2021_01_07_425675 42 4 a a DT 10_1101-2021_01_07_425675 42 5 panel panel NN 10_1101-2021_01_07_425675 42 6 of of IN 10_1101-2021_01_07_425675 42 7 9 9 CD 10_1101-2021_01_07_425675 42 8 proteases protease NNS 10_1101-2021_01_07_425675 42 9 with with IN 10_1101-2021_01_07_425675 42 10 activity activity NN 10_1101-2021_01_07_425675 42 11 at at IN 10_1101-2021_01_07_425675 42 12 pH pH NNP 10_1101-2021_01_07_425675 42 13 7.5 7.5 CD 10_1101-2021_01_07_425675 42 14 - - SYM 10_1101-2021_01_07_425675 42 15 8.5 8.5 CD 10_1101-2021_01_07_425675 42 16 , , , 10_1101-2021_01_07_425675 42 17 so so IN 10_1101-2021_01_07_425675 42 18 that that IN 10_1101-2021_01_07_425675 42 19 the the DT 10_1101-2021_01_07_425675 42 20 denatured denatured JJ 10_1101-2021_01_07_425675 42 21 , , , 10_1101-2021_01_07_425675 42 22 reduced reduce VBN 10_1101-2021_01_07_425675 42 23 and and CC 10_1101-2021_01_07_425675 42 24 97 97 CD 10_1101-2021_01_07_425675 42 25 alkylated alkylated JJ 10_1101-2021_01_07_425675 42 26 antibodies antibody NNS 10_1101-2021_01_07_425675 42 27 could could MD 10_1101-2021_01_07_425675 42 28 be be VB 10_1101-2021_01_07_425675 42 29 easily easily RB 10_1101-2021_01_07_425675 42 30 split split VBN 10_1101-2021_01_07_425675 42 31 for for IN 10_1101-2021_01_07_425675 42 32 parallel parallel JJ 10_1101-2021_01_07_425675 42 33 digestion digestion NN 10_1101-2021_01_07_425675 42 34 under under IN 10_1101-2021_01_07_425675 42 35 the the DT 10_1101-2021_01_07_425675 42 36 same same JJ 10_1101-2021_01_07_425675 42 37 buffer buffer NN 10_1101-2021_01_07_425675 42 38 conditions condition NNS 10_1101-2021_01_07_425675 42 39 . . . 10_1101-2021_01_07_425675 43 1 98 98 CD 10_1101-2021_01_07_425675 43 2 These these DT 10_1101-2021_01_07_425675 43 3 proteases protease NNS 10_1101-2021_01_07_425675 43 4 ( ( -LRB- 10_1101-2021_01_07_425675 43 5 with with IN 10_1101-2021_01_07_425675 43 6 indicated indicate VBN 10_1101-2021_01_07_425675 43 7 cleavage cleavage NN 10_1101-2021_01_07_425675 43 8 specificities specificity NNS 10_1101-2021_01_07_425675 43 9 ) ) -RRB- 10_1101-2021_01_07_425675 43 10 included include VBD 10_1101-2021_01_07_425675 43 11 : : : 10_1101-2021_01_07_425675 43 12 trypsin trypsin NNP 10_1101-2021_01_07_425675 43 13 ( ( -LRB- 10_1101-2021_01_07_425675 43 14 C c NN 10_1101-2021_01_07_425675 43 15 - - HYPH 10_1101-2021_01_07_425675 43 16 terminal terminal NN 10_1101-2021_01_07_425675 43 17 of of IN 10_1101-2021_01_07_425675 43 18 R R NNP 10_1101-2021_01_07_425675 43 19 / / SYM 10_1101-2021_01_07_425675 43 20 K K NNP 10_1101-2021_01_07_425675 43 21 ) ) -RRB- 10_1101-2021_01_07_425675 43 22 , , , 10_1101-2021_01_07_425675 43 23 99 99 CD 10_1101-2021_01_07_425675 43 24 chymotrypsin chymotrypsin NN 10_1101-2021_01_07_425675 43 25 ( ( -LRB- 10_1101-2021_01_07_425675 43 26 C c NN 10_1101-2021_01_07_425675 43 27 - - HYPH 10_1101-2021_01_07_425675 43 28 terminal terminal NN 10_1101-2021_01_07_425675 43 29 of of IN 10_1101-2021_01_07_425675 43 30 F F NNP 10_1101-2021_01_07_425675 43 31 / / SYM 10_1101-2021_01_07_425675 43 32 Y Y NNP 10_1101-2021_01_07_425675 43 33 / / SYM 10_1101-2021_01_07_425675 43 34 W W NNP 10_1101-2021_01_07_425675 43 35 / / SYM 10_1101-2021_01_07_425675 43 36 M M NNP 10_1101-2021_01_07_425675 43 37 / / SYM 10_1101-2021_01_07_425675 43 38 L L NNP 10_1101-2021_01_07_425675 43 39 ) ) -RRB- 10_1101-2021_01_07_425675 43 40 , , , 10_1101-2021_01_07_425675 43 41 α α NNP 10_1101-2021_01_07_425675 43 42 - - HYPH 10_1101-2021_01_07_425675 43 43 lytic lytic NN 10_1101-2021_01_07_425675 43 44 protease protease NN 10_1101-2021_01_07_425675 43 45 ( ( -LRB- 10_1101-2021_01_07_425675 43 46 C c NN 10_1101-2021_01_07_425675 43 47 - - HYPH 10_1101-2021_01_07_425675 43 48 terminal terminal NN 10_1101-2021_01_07_425675 43 49 of of IN 10_1101-2021_01_07_425675 43 50 T t NN 10_1101-2021_01_07_425675 43 51 / / , 10_1101-2021_01_07_425675 43 52 A A NNP 10_1101-2021_01_07_425675 43 53 / / SYM 10_1101-2021_01_07_425675 43 54 S S NNP 10_1101-2021_01_07_425675 43 55 / / SYM 10_1101-2021_01_07_425675 43 56 V V NNP 10_1101-2021_01_07_425675 43 57 ) ) -RRB- 10_1101-2021_01_07_425675 43 58 , , , 10_1101-2021_01_07_425675 43 59 elastase elastase VB 10_1101-2021_01_07_425675 43 60 100 100 CD 10_1101-2021_01_07_425675 43 61 ( ( -LRB- 10_1101-2021_01_07_425675 43 62 unspecific unspecific NNP 10_1101-2021_01_07_425675 43 63 ) ) -RRB- 10_1101-2021_01_07_425675 43 64 , , , 10_1101-2021_01_07_425675 43 65 thermolysin thermolysin NNP 10_1101-2021_01_07_425675 43 66 ( ( -LRB- 10_1101-2021_01_07_425675 43 67 unspecific unspecific NNP 10_1101-2021_01_07_425675 43 68 ) ) -RRB- 10_1101-2021_01_07_425675 43 69 , , , 10_1101-2021_01_07_425675 43 70 lysN lysn JJ 10_1101-2021_01_07_425675 43 71 ( ( -LRB- 10_1101-2021_01_07_425675 43 72 N n NN 10_1101-2021_01_07_425675 43 73 - - NN 10_1101-2021_01_07_425675 43 74 terminal terminal NN 10_1101-2021_01_07_425675 43 75 of of IN 10_1101-2021_01_07_425675 43 76 K K NNP 10_1101-2021_01_07_425675 43 77 ) ) -RRB- 10_1101-2021_01_07_425675 43 78 , , , 10_1101-2021_01_07_425675 43 79 lysC lysc ADD 10_1101-2021_01_07_425675 43 80 ( ( -LRB- 10_1101-2021_01_07_425675 43 81 C c NN 10_1101-2021_01_07_425675 43 82 - - HYPH 10_1101-2021_01_07_425675 43 83 terminal terminal NN 10_1101-2021_01_07_425675 43 84 of of IN 10_1101-2021_01_07_425675 43 85 K K NNP 10_1101-2021_01_07_425675 43 86 ) ) -RRB- 10_1101-2021_01_07_425675 43 87 , , , 10_1101-2021_01_07_425675 43 88 aspN aspn IN 10_1101-2021_01_07_425675 43 89 ( ( -LRB- 10_1101-2021_01_07_425675 43 90 N-101 n-101 UH 10_1101-2021_01_07_425675 43 91 terminal terminal NN 10_1101-2021_01_07_425675 43 92 of of IN 10_1101-2021_01_07_425675 43 93 D d NN 10_1101-2021_01_07_425675 43 94 / / SYM 10_1101-2021_01_07_425675 43 95 E e NN 10_1101-2021_01_07_425675 43 96 ) ) -RRB- 10_1101-2021_01_07_425675 43 97 , , , 10_1101-2021_01_07_425675 43 98 and and CC 10_1101-2021_01_07_425675 43 99 gluC gluC NNP 10_1101-2021_01_07_425675 43 100 ( ( -LRB- 10_1101-2021_01_07_425675 43 101 C c NN 10_1101-2021_01_07_425675 43 102 - - HYPH 10_1101-2021_01_07_425675 43 103 terminal terminal NN 10_1101-2021_01_07_425675 43 104 of of IN 10_1101-2021_01_07_425675 43 105 D d NN 10_1101-2021_01_07_425675 43 106 / / SYM 10_1101-2021_01_07_425675 43 107 E e NN 10_1101-2021_01_07_425675 43 108 ) ) -RRB- 10_1101-2021_01_07_425675 43 109 . . . 10_1101-2021_01_07_425675 44 1 Correct correct JJ 10_1101-2021_01_07_425675 44 2 placement placement NN 10_1101-2021_01_07_425675 44 3 or or CC 10_1101-2021_01_07_425675 44 4 assembly assembly NN 10_1101-2021_01_07_425675 44 5 of of IN 10_1101-2021_01_07_425675 44 6 peptide peptide NN 10_1101-2021_01_07_425675 44 7 reads read VBZ 10_1101-2021_01_07_425675 44 8 102 102 CD 10_1101-2021_01_07_425675 44 9 is be VBZ 10_1101-2021_01_07_425675 44 10 a a DT 10_1101-2021_01_07_425675 44 11 common common JJ 10_1101-2021_01_07_425675 44 12 challenge challenge NN 10_1101-2021_01_07_425675 44 13 in in IN 10_1101-2021_01_07_425675 44 14 de de FW 10_1101-2021_01_07_425675 44 15 novo novo NNP 10_1101-2021_01_07_425675 44 16 sequencing sequencing NN 10_1101-2021_01_07_425675 44 17 , , , 10_1101-2021_01_07_425675 44 18 which which WDT 10_1101-2021_01_07_425675 44 19 can can MD 10_1101-2021_01_07_425675 44 20 be be VB 10_1101-2021_01_07_425675 44 21 facilitated facilitate VBN 10_1101-2021_01_07_425675 44 22 by by IN 10_1101-2021_01_07_425675 44 23 sufficient sufficient JJ 10_1101-2021_01_07_425675 44 24 overlap overlap NN 10_1101-2021_01_07_425675 44 25 103 103 CD 10_1101-2021_01_07_425675 44 26 between between IN 10_1101-2021_01_07_425675 44 27 the the DT 10_1101-2021_01_07_425675 44 28 peptide peptide NN 10_1101-2021_01_07_425675 44 29 reads read VBZ 10_1101-2021_01_07_425675 44 30 . . . 10_1101-2021_01_07_425675 45 1 This this DT 10_1101-2021_01_07_425675 45 2 favors favor VBZ 10_1101-2021_01_07_425675 45 3 the the DT 10_1101-2021_01_07_425675 45 4 occurrence occurrence NN 10_1101-2021_01_07_425675 45 5 of of IN 10_1101-2021_01_07_425675 45 6 missed miss VBN 10_1101-2021_01_07_425675 45 7 cleavages cleavage NNS 10_1101-2021_01_07_425675 45 8 and and CC 10_1101-2021_01_07_425675 45 9 longer long JJR 10_1101-2021_01_07_425675 45 10 reads read VBZ 10_1101-2021_01_07_425675 45 11 , , , 10_1101-2021_01_07_425675 45 12 so so RB 10_1101-2021_01_07_425675 45 13 104 104 CD 10_1101-2021_01_07_425675 45 14 we -PRON- PRP 10_1101-2021_01_07_425675 45 15 opted opt VBD 10_1101-2021_01_07_425675 45 16 to to TO 10_1101-2021_01_07_425675 45 17 perform perform VB 10_1101-2021_01_07_425675 45 18 a a DT 10_1101-2021_01_07_425675 45 19 brief brief JJ 10_1101-2021_01_07_425675 45 20 4-hour 4-hour CD 10_1101-2021_01_07_425675 45 21 digestion digestion NN 10_1101-2021_01_07_425675 45 22 . . . 10_1101-2021_01_07_425675 46 1 Following follow VBG 10_1101-2021_01_07_425675 46 2 digestion digestion NN 10_1101-2021_01_07_425675 46 3 , , , 10_1101-2021_01_07_425675 46 4 SDC SDC NNP 10_1101-2021_01_07_425675 46 5 is be VBZ 10_1101-2021_01_07_425675 46 6 removed remove VBN 10_1101-2021_01_07_425675 46 7 by by IN 10_1101-2021_01_07_425675 46 8 precipitation precipitation NN 10_1101-2021_01_07_425675 46 9 105 105 CD 10_1101-2021_01_07_425675 46 10 and and CC 10_1101-2021_01_07_425675 46 11 the the DT 10_1101-2021_01_07_425675 46 12 peptide peptide JJ 10_1101-2021_01_07_425675 46 13 supernatant supernatant JJ 10_1101-2021_01_07_425675 46 14 is be VBZ 10_1101-2021_01_07_425675 46 15 desalted desalt VBN 10_1101-2021_01_07_425675 46 16 , , , 10_1101-2021_01_07_425675 46 17 ready ready JJ 10_1101-2021_01_07_425675 46 18 for for IN 10_1101-2021_01_07_425675 46 19 LC LC NNP 10_1101-2021_01_07_425675 46 20 - - HYPH 10_1101-2021_01_07_425675 46 21 MS MS NNP 10_1101-2021_01_07_425675 46 22 / / SYM 10_1101-2021_01_07_425675 46 23 MS MS NNP 10_1101-2021_01_07_425675 46 24 analysis analysis NN 10_1101-2021_01_07_425675 46 25 . . . 10_1101-2021_01_07_425675 47 1 The the DT 10_1101-2021_01_07_425675 47 2 resulting result VBG 10_1101-2021_01_07_425675 47 3 raw raw JJ 10_1101-2021_01_07_425675 47 4 data datum NNS 10_1101-2021_01_07_425675 47 5 106 106 CD 10_1101-2021_01_07_425675 47 6 was be VBD 10_1101-2021_01_07_425675 47 7 used use VBN 10_1101-2021_01_07_425675 47 8 for for IN 10_1101-2021_01_07_425675 47 9 automated automate VBN 10_1101-2021_01_07_425675 47 10 de de NNP 10_1101-2021_01_07_425675 47 11 novo novo NNP 10_1101-2021_01_07_425675 47 12 sequencing sequencing NN 10_1101-2021_01_07_425675 47 13 with with IN 10_1101-2021_01_07_425675 47 14 the the DT 10_1101-2021_01_07_425675 47 15 Supernovo Supernovo NNP 10_1101-2021_01_07_425675 47 16 software software NN 10_1101-2021_01_07_425675 47 17 package package NN 10_1101-2021_01_07_425675 47 18 . . . 10_1101-2021_01_07_425675 48 1 107 107 CD 10_1101-2021_01_07_425675 48 2 As as IN 10_1101-2021_01_07_425675 48 3 peptide peptide JJ 10_1101-2021_01_07_425675 48 4 fragmentation fragmentation NN 10_1101-2021_01_07_425675 48 5 is be VBZ 10_1101-2021_01_07_425675 48 6 dependent dependent JJ 10_1101-2021_01_07_425675 48 7 on on IN 10_1101-2021_01_07_425675 48 8 many many JJ 10_1101-2021_01_07_425675 48 9 factors factor NNS 10_1101-2021_01_07_425675 48 10 like like IN 10_1101-2021_01_07_425675 48 11 length length NN 10_1101-2021_01_07_425675 48 12 , , , 10_1101-2021_01_07_425675 48 13 charge charge NN 10_1101-2021_01_07_425675 48 14 state state NN 10_1101-2021_01_07_425675 48 15 , , , 10_1101-2021_01_07_425675 48 16 composition composition NN 10_1101-2021_01_07_425675 48 17 and and CC 10_1101-2021_01_07_425675 48 18 108 108 CD 10_1101-2021_01_07_425675 48 19 sequence sequence NN 10_1101-2021_01_07_425675 48 20 26 26 CD 10_1101-2021_01_07_425675 48 21 , , , 10_1101-2021_01_07_425675 48 22 we -PRON- PRP 10_1101-2021_01_07_425675 48 23 needed need VBD 10_1101-2021_01_07_425675 48 24 a a DT 10_1101-2021_01_07_425675 48 25 versatile versatile JJ 10_1101-2021_01_07_425675 48 26 fragmentation fragmentation NN 10_1101-2021_01_07_425675 48 27 strategy strategy NN 10_1101-2021_01_07_425675 48 28 to to TO 10_1101-2021_01_07_425675 48 29 accommodate accommodate VB 10_1101-2021_01_07_425675 48 30 the the DT 10_1101-2021_01_07_425675 48 31 diversity diversity NN 10_1101-2021_01_07_425675 48 32 of of IN 10_1101-2021_01_07_425675 48 33 109 109 CD 10_1101-2021_01_07_425675 48 34 antibody antibody NN 10_1101-2021_01_07_425675 48 35 - - HYPH 10_1101-2021_01_07_425675 48 36 derived derive VBN 10_1101-2021_01_07_425675 48 37 peptides peptide NNS 10_1101-2021_01_07_425675 48 38 generated generate VBN 10_1101-2021_01_07_425675 48 39 by by IN 10_1101-2021_01_07_425675 48 40 the the DT 10_1101-2021_01_07_425675 48 41 9 9 CD 10_1101-2021_01_07_425675 48 42 proteases protease NNS 10_1101-2021_01_07_425675 48 43 . . . 10_1101-2021_01_07_425675 49 1 We -PRON- PRP 10_1101-2021_01_07_425675 49 2 opted opt VBD 10_1101-2021_01_07_425675 49 3 for for IN 10_1101-2021_01_07_425675 49 4 a a DT 10_1101-2021_01_07_425675 49 5 dual dual JJ 10_1101-2021_01_07_425675 49 6 fragmentation fragmentation NN 10_1101-2021_01_07_425675 49 7 110 110 CD 10_1101-2021_01_07_425675 49 8 scheme scheme NN 10_1101-2021_01_07_425675 49 9 that that WDT 10_1101-2021_01_07_425675 49 10 applies apply VBZ 10_1101-2021_01_07_425675 49 11 both both DT 10_1101-2021_01_07_425675 49 12 stepped step VBD 10_1101-2021_01_07_425675 49 13 high high JJ 10_1101-2021_01_07_425675 49 14 - - HYPH 10_1101-2021_01_07_425675 49 15 energy energy NN 10_1101-2021_01_07_425675 49 16 collision collision NN 10_1101-2021_01_07_425675 49 17 dissociation dissociation NN 10_1101-2021_01_07_425675 49 18 ( ( -LRB- 10_1101-2021_01_07_425675 49 19 stepped step VBD 10_1101-2021_01_07_425675 49 20 HCD HCD NNP 10_1101-2021_01_07_425675 49 21 ) ) -RRB- 10_1101-2021_01_07_425675 49 22 and and CC 10_1101-2021_01_07_425675 49 23 electron electron NN 10_1101-2021_01_07_425675 49 24 111 111 CD 10_1101-2021_01_07_425675 49 25 transfer transfer NN 10_1101-2021_01_07_425675 49 26 high high JJ 10_1101-2021_01_07_425675 49 27 - - HYPH 10_1101-2021_01_07_425675 49 28 energy energy NN 10_1101-2021_01_07_425675 49 29 collision collision NN 10_1101-2021_01_07_425675 49 30 dissociation dissociation NN 10_1101-2021_01_07_425675 49 31 ( ( -LRB- 10_1101-2021_01_07_425675 49 32 EThcD EThcD NNP 10_1101-2021_01_07_425675 49 33 ) ) -RRB- 10_1101-2021_01_07_425675 49 34 on on IN 10_1101-2021_01_07_425675 49 35 all all DT 10_1101-2021_01_07_425675 49 36 peptide peptide JJ 10_1101-2021_01_07_425675 49 37 precursors precursor NNS 10_1101-2021_01_07_425675 49 38 27 27 CD 10_1101-2021_01_07_425675 49 39 - - SYM 10_1101-2021_01_07_425675 49 40 29 29 CD 10_1101-2021_01_07_425675 49 41 . . . 10_1101-2021_01_07_425675 50 1 The the DT 10_1101-2021_01_07_425675 50 2 stepped step VBN 10_1101-2021_01_07_425675 50 3 112 112 CD 10_1101-2021_01_07_425675 50 4 HCD HCD NNP 10_1101-2021_01_07_425675 50 5 fragmentation fragmentation NN 10_1101-2021_01_07_425675 50 6 includes include VBZ 10_1101-2021_01_07_425675 50 7 three three CD 10_1101-2021_01_07_425675 50 8 collision collision NN 10_1101-2021_01_07_425675 50 9 energies energy NNS 10_1101-2021_01_07_425675 50 10 to to TO 10_1101-2021_01_07_425675 50 11 cover cover VB 10_1101-2021_01_07_425675 50 12 multiple multiple JJ 10_1101-2021_01_07_425675 50 13 dissociation dissociation NN 10_1101-2021_01_07_425675 50 14 regimes regime NNS 10_1101-2021_01_07_425675 50 15 and and CC 10_1101-2021_01_07_425675 50 16 113 113 CD 10_1101-2021_01_07_425675 50 17 the the DT 10_1101-2021_01_07_425675 50 18 EThcD EThcD NNP 10_1101-2021_01_07_425675 50 19 fragmentation fragmentation NN 10_1101-2021_01_07_425675 50 20 works work VBZ 10_1101-2021_01_07_425675 50 21 especially especially RB 10_1101-2021_01_07_425675 50 22 well well RB 10_1101-2021_01_07_425675 50 23 for for IN 10_1101-2021_01_07_425675 50 24 higher high JJR 10_1101-2021_01_07_425675 50 25 charge charge NN 10_1101-2021_01_07_425675 50 26 states state NNS 10_1101-2021_01_07_425675 50 27 , , , 10_1101-2021_01_07_425675 50 28 also also RB 10_1101-2021_01_07_425675 50 29 adding add VBG 10_1101-2021_01_07_425675 50 30 114 114 CD 10_1101-2021_01_07_425675 50 31 complementary complementary JJ 10_1101-2021_01_07_425675 50 32 c c NN 10_1101-2021_01_07_425675 50 33 / / SYM 10_1101-2021_01_07_425675 50 34 z z NNP 10_1101-2021_01_07_425675 50 35 ions ion NNS 10_1101-2021_01_07_425675 50 36 for for IN 10_1101-2021_01_07_425675 50 37 maximum maximum JJ 10_1101-2021_01_07_425675 50 38 sequence sequence NN 10_1101-2021_01_07_425675 50 39 coverage coverage NN 10_1101-2021_01_07_425675 50 40 . . . 10_1101-2021_01_07_425675 51 1 115 115 CD 10_1101-2021_01_07_425675 51 2 We -PRON- PRP 10_1101-2021_01_07_425675 51 3 used use VBD 10_1101-2021_01_07_425675 51 4 the the DT 10_1101-2021_01_07_425675 51 5 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 51 6 antibody antibody NN 10_1101-2021_01_07_425675 51 7 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 51 8 ( ( -LRB- 10_1101-2021_01_07_425675 51 9 also also RB 10_1101-2021_01_07_425675 51 10 known know VBN 10_1101-2021_01_07_425675 51 11 as as IN 10_1101-2021_01_07_425675 51 12 Trastuzumab Trastuzumab NNP 10_1101-2021_01_07_425675 51 13 ) ) -RRB- 10_1101-2021_01_07_425675 51 14 as as IN 10_1101-2021_01_07_425675 51 15 a a DT 10_1101-2021_01_07_425675 51 16 benchmark benchmark NN 10_1101-2021_01_07_425675 51 17 to to TO 10_1101-2021_01_07_425675 51 18 116 116 CD 10_1101-2021_01_07_425675 51 19 test test NN 10_1101-2021_01_07_425675 51 20 our -PRON- PRP$ 10_1101-2021_01_07_425675 51 21 protocol protocol JJ 10_1101-2021_01_07_425675 51 22 30 30 CD 10_1101-2021_01_07_425675 51 23 - - SYM 10_1101-2021_01_07_425675 51 24 31 31 CD 10_1101-2021_01_07_425675 51 25 . . . 10_1101-2021_01_07_425675 52 1 From from IN 10_1101-2021_01_07_425675 52 2 the the DT 10_1101-2021_01_07_425675 52 3 total total JJ 10_1101-2021_01_07_425675 52 4 dataset dataset NN 10_1101-2021_01_07_425675 52 5 of of IN 10_1101-2021_01_07_425675 52 6 9 9 CD 10_1101-2021_01_07_425675 52 7 proteases protease NNS 10_1101-2021_01_07_425675 52 8 , , , 10_1101-2021_01_07_425675 52 9 we -PRON- PRP 10_1101-2021_01_07_425675 52 10 collected collect VBD 10_1101-2021_01_07_425675 52 11 4408 4408 CD 10_1101-2021_01_07_425675 52 12 peptide peptide NN 10_1101-2021_01_07_425675 52 13 reads read VBZ 10_1101-2021_01_07_425675 52 14 117 117 CD 10_1101-2021_01_07_425675 52 15 ( ( -LRB- 10_1101-2021_01_07_425675 52 16 defined define VBN 10_1101-2021_01_07_425675 52 17 as as IN 10_1101-2021_01_07_425675 52 18 peptides peptide NNS 10_1101-2021_01_07_425675 52 19 with with IN 10_1101-2021_01_07_425675 52 20 score score NN 10_1101-2021_01_07_425675 52 21 > > XX 10_1101-2021_01_07_425675 52 22 = = SYM 10_1101-2021_01_07_425675 52 23 500 500 CD 10_1101-2021_01_07_425675 52 24 , , , 10_1101-2021_01_07_425675 52 25 see see VB 10_1101-2021_01_07_425675 52 26 methods method NNS 10_1101-2021_01_07_425675 52 27 for for IN 10_1101-2021_01_07_425675 52 28 details detail NNS 10_1101-2021_01_07_425675 52 29 ) ) -RRB- 10_1101-2021_01_07_425675 52 30 , , , 10_1101-2021_01_07_425675 52 31 2866 2866 CD 10_1101-2021_01_07_425675 52 32 of of IN 10_1101-2021_01_07_425675 52 33 which which WDT 10_1101-2021_01_07_425675 52 34 with with IN 10_1101-2021_01_07_425675 52 35 superior superior JJ 10_1101-2021_01_07_425675 52 36 118 118 CD 10_1101-2021_01_07_425675 52 37 stepped step VBD 10_1101-2021_01_07_425675 52 38 HCD HCD NNP 10_1101-2021_01_07_425675 52 39 fragmentation fragmentation NN 10_1101-2021_01_07_425675 52 40 , , , 10_1101-2021_01_07_425675 52 41 and and CC 10_1101-2021_01_07_425675 52 42 1722 1722 CD 10_1101-2021_01_07_425675 52 43 with with IN 10_1101-2021_01_07_425675 52 44 superior superior JJ 10_1101-2021_01_07_425675 52 45 EThcD EThcD NNP 10_1101-2021_01_07_425675 52 46 fragmentation fragmentation NN 10_1101-2021_01_07_425675 52 47 ( ( -LRB- 10_1101-2021_01_07_425675 52 48 see see VB 10_1101-2021_01_07_425675 52 49 Table table NN 10_1101-2021_01_07_425675 52 50 S1 s1 NN 10_1101-2021_01_07_425675 52 51 ) ) -RRB- 10_1101-2021_01_07_425675 52 52 . . . 10_1101-2021_01_07_425675 53 1 119 119 CD 10_1101-2021_01_07_425675 53 2 Sequence sequence NN 10_1101-2021_01_07_425675 53 3 coverage coverage NN 10_1101-2021_01_07_425675 53 4 was be VBD 10_1101-2021_01_07_425675 53 5 100 100 CD 10_1101-2021_01_07_425675 53 6 % % NN 10_1101-2021_01_07_425675 53 7 in in IN 10_1101-2021_01_07_425675 53 8 both both CC 10_1101-2021_01_07_425675 53 9 heavy heavy JJ 10_1101-2021_01_07_425675 53 10 and and CC 10_1101-2021_01_07_425675 53 11 light light JJ 10_1101-2021_01_07_425675 53 12 chains chain NNS 10_1101-2021_01_07_425675 53 13 across across IN 10_1101-2021_01_07_425675 53 14 the the DT 10_1101-2021_01_07_425675 53 15 variable variable JJ 10_1101-2021_01_07_425675 53 16 and and CC 10_1101-2021_01_07_425675 53 17 constant constant JJ 10_1101-2021_01_07_425675 53 18 120 120 CD 10_1101-2021_01_07_425675 53 19 domains domain NNS 10_1101-2021_01_07_425675 53 20 ( ( -LRB- 10_1101-2021_01_07_425675 53 21 see see VB 10_1101-2021_01_07_425675 53 22 Figures Figures NNP 10_1101-2021_01_07_425675 53 23 S1 S1 NNS 10_1101-2021_01_07_425675 53 24 and and CC 10_1101-2021_01_07_425675 53 25 S2 S2 NNP 10_1101-2021_01_07_425675 53 26 ) ) -RRB- 10_1101-2021_01_07_425675 53 27 . . . 10_1101-2021_01_07_425675 54 1 The the DT 10_1101-2021_01_07_425675 54 2 median median JJ 10_1101-2021_01_07_425675 54 3 depth depth NN 10_1101-2021_01_07_425675 54 4 of of IN 10_1101-2021_01_07_425675 54 5 coverage coverage NN 10_1101-2021_01_07_425675 54 6 was be VBD 10_1101-2021_01_07_425675 54 7 148 148 CD 10_1101-2021_01_07_425675 54 8 overall overall JJ 10_1101-2021_01_07_425675 54 9 and and CC 10_1101-2021_01_07_425675 54 10 slightly slightly RB 10_1101-2021_01_07_425675 54 11 121 121 CD 10_1101-2021_01_07_425675 54 12 higher high JJR 10_1101-2021_01_07_425675 54 13 in in IN 10_1101-2021_01_07_425675 54 14 the the DT 10_1101-2021_01_07_425675 54 15 light light JJ 10_1101-2021_01_07_425675 54 16 chain chain NN 10_1101-2021_01_07_425675 54 17 ( ( -LRB- 10_1101-2021_01_07_425675 54 18 see see VB 10_1101-2021_01_07_425675 54 19 Table table NN 10_1101-2021_01_07_425675 54 20 S1 S1 NNS 10_1101-2021_01_07_425675 54 21 and and CC 10_1101-2021_01_07_425675 54 22 Figure Figure NNP 10_1101-2021_01_07_425675 54 23 S1 S1 NNS 10_1101-2021_01_07_425675 54 24 - - : 10_1101-2021_01_07_425675 54 25 2 2 CD 10_1101-2021_01_07_425675 54 26 ) ) -RRB- 10_1101-2021_01_07_425675 54 27 . . . 10_1101-2021_01_07_425675 55 1 The the DT 10_1101-2021_01_07_425675 55 2 median median JJ 10_1101-2021_01_07_425675 55 3 depth depth NN 10_1101-2021_01_07_425675 55 4 of of IN 10_1101-2021_01_07_425675 55 5 coverage coverage NN 10_1101-2021_01_07_425675 55 6 in in IN 10_1101-2021_01_07_425675 55 7 the the DT 10_1101-2021_01_07_425675 55 8 122 122 CD 10_1101-2021_01_07_425675 55 9 CDRs cdr NNS 10_1101-2021_01_07_425675 55 10 of of IN 10_1101-2021_01_07_425675 55 11 both both DT 10_1101-2021_01_07_425675 55 12 chains chain NNS 10_1101-2021_01_07_425675 55 13 ranged range VBD 10_1101-2021_01_07_425675 55 14 from from IN 10_1101-2021_01_07_425675 55 15 42 42 CD 10_1101-2021_01_07_425675 55 16 to to IN 10_1101-2021_01_07_425675 55 17 210 210 CD 10_1101-2021_01_07_425675 55 18 . . . 10_1101-2021_01_07_425675 56 1 123 123 CD 10_1101-2021_01_07_425675 56 2 .CC .CC NFP 10_1101-2021_01_07_425675 56 3 - - : 10_1101-2021_01_07_425675 56 4 BY by IN 10_1101-2021_01_07_425675 56 5 4.0 4.0 CD 10_1101-2021_01_07_425675 56 6 International International NNP 10_1101-2021_01_07_425675 56 7 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 56 8 under under IN 10_1101-2021_01_07_425675 56 9 a a DT 10_1101-2021_01_07_425675 56 10 ( ( -LRB- 10_1101-2021_01_07_425675 56 11 which which WDT 10_1101-2021_01_07_425675 56 12 was be VBD 10_1101-2021_01_07_425675 56 13 not not RB 10_1101-2021_01_07_425675 56 14 certified certify VBN 10_1101-2021_01_07_425675 56 15 by by IN 10_1101-2021_01_07_425675 56 16 peer peer NN 10_1101-2021_01_07_425675 56 17 review review NN 10_1101-2021_01_07_425675 56 18 ) ) -RRB- 10_1101-2021_01_07_425675 56 19 is be VBZ 10_1101-2021_01_07_425675 56 20 the the DT 10_1101-2021_01_07_425675 56 21 author author NN 10_1101-2021_01_07_425675 56 22 / / SYM 10_1101-2021_01_07_425675 56 23 funder funder NN 10_1101-2021_01_07_425675 56 24 , , , 10_1101-2021_01_07_425675 56 25 who who WP 10_1101-2021_01_07_425675 56 26 has have VBZ 10_1101-2021_01_07_425675 56 27 granted grant VBN 10_1101-2021_01_07_425675 56 28 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 56 29 a a DT 10_1101-2021_01_07_425675 56 30 license license NN 10_1101-2021_01_07_425675 56 31 to to TO 10_1101-2021_01_07_425675 56 32 display display VB 10_1101-2021_01_07_425675 56 33 the the DT 10_1101-2021_01_07_425675 56 34 preprint preprint NN 10_1101-2021_01_07_425675 56 35 in in IN 10_1101-2021_01_07_425675 56 36 perpetuity perpetuity NN 10_1101-2021_01_07_425675 56 37 . . . 10_1101-2021_01_07_425675 57 1 It -PRON- PRP 10_1101-2021_01_07_425675 57 2 is be VBZ 10_1101-2021_01_07_425675 57 3 made make VBN 10_1101-2021_01_07_425675 57 4 The the DT 10_1101-2021_01_07_425675 57 5 copyright copyright NN 10_1101-2021_01_07_425675 57 6 holder holder NN 10_1101-2021_01_07_425675 57 7 for for IN 10_1101-2021_01_07_425675 57 8 this this DT 10_1101-2021_01_07_425675 57 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 57 10 version version NN 10_1101-2021_01_07_425675 57 11 posted post VBD 10_1101-2021_01_07_425675 57 12 January January NNP 10_1101-2021_01_07_425675 57 13 8 8 CD 10_1101-2021_01_07_425675 57 14 , , , 10_1101-2021_01_07_425675 57 15 2021 2021 CD 10_1101-2021_01_07_425675 57 16 . . . 10_1101-2021_01_07_425675 57 17 ; ; : 10_1101-2021_01_07_425675 57 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 57 19 : : : 10_1101-2021_01_07_425675 57 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 57 21 preprint preprint NN 10_1101-2021_01_07_425675 57 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 57 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 57 24 6 6 CD 10_1101-2021_01_07_425675 57 25 124 124 CD 10_1101-2021_01_07_425675 57 26 Figure Figure NNP 10_1101-2021_01_07_425675 57 27 1 1 CD 10_1101-2021_01_07_425675 57 28 . . . 10_1101-2021_01_07_425675 57 29 mass mass NNP 10_1101-2021_01_07_425675 57 30 spectrometry spectrometry NNP 10_1101-2021_01_07_425675 57 31 - - HYPH 10_1101-2021_01_07_425675 57 32 based base VBN 10_1101-2021_01_07_425675 57 33 de de NNP 10_1101-2021_01_07_425675 57 34 novo novo NNP 10_1101-2021_01_07_425675 57 35 sequencing sequencing NN 10_1101-2021_01_07_425675 57 36 of of IN 10_1101-2021_01_07_425675 57 37 the the DT 10_1101-2021_01_07_425675 57 38 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 57 39 antibody antibody NN 10_1101-2021_01_07_425675 57 40 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 57 41 . . . 10_1101-2021_01_07_425675 58 1 The the DT 10_1101-2021_01_07_425675 58 2 125 125 CD 10_1101-2021_01_07_425675 58 3 variable variable JJ 10_1101-2021_01_07_425675 58 4 regions region NNS 10_1101-2021_01_07_425675 58 5 of of IN 10_1101-2021_01_07_425675 58 6 the the DT 10_1101-2021_01_07_425675 58 7 Heavy heavy JJ 10_1101-2021_01_07_425675 58 8 ( ( -LRB- 10_1101-2021_01_07_425675 58 9 A a NN 10_1101-2021_01_07_425675 58 10 ) ) -RRB- 10_1101-2021_01_07_425675 58 11 and and CC 10_1101-2021_01_07_425675 58 12 Light Light NNP 10_1101-2021_01_07_425675 58 13 Chains Chains NNPS 10_1101-2021_01_07_425675 58 14 ( ( -LRB- 10_1101-2021_01_07_425675 58 15 B b NN 10_1101-2021_01_07_425675 58 16 ) ) -RRB- 10_1101-2021_01_07_425675 58 17 are be VBP 10_1101-2021_01_07_425675 58 18 shown show VBN 10_1101-2021_01_07_425675 58 19 . . . 10_1101-2021_01_07_425675 59 1 The the DT 10_1101-2021_01_07_425675 59 2 MS MS NNP 10_1101-2021_01_07_425675 59 3 - - HYPH 10_1101-2021_01_07_425675 59 4 based base VBN 10_1101-2021_01_07_425675 59 5 sequence sequence NN 10_1101-2021_01_07_425675 59 6 is be VBZ 10_1101-2021_01_07_425675 59 7 shown show VBN 10_1101-2021_01_07_425675 59 8 126 126 CD 10_1101-2021_01_07_425675 59 9 alongside alongside IN 10_1101-2021_01_07_425675 59 10 the the DT 10_1101-2021_01_07_425675 59 11 known known JJ 10_1101-2021_01_07_425675 59 12 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 59 13 sequence sequence NN 10_1101-2021_01_07_425675 59 14 , , , 10_1101-2021_01_07_425675 59 15 with with IN 10_1101-2021_01_07_425675 59 16 differences difference NNS 10_1101-2021_01_07_425675 59 17 highlighted highlight VBN 10_1101-2021_01_07_425675 59 18 by by IN 10_1101-2021_01_07_425675 59 19 asterisks asterisk NNS 10_1101-2021_01_07_425675 59 20 ( ( -LRB- 10_1101-2021_01_07_425675 59 21 * * NFP 10_1101-2021_01_07_425675 59 22 ) ) -RRB- 10_1101-2021_01_07_425675 59 23 . . . 10_1101-2021_01_07_425675 60 1 Exemplary Exemplary NNP 10_1101-2021_01_07_425675 60 2 MS MS NNP 10_1101-2021_01_07_425675 60 3 / / SYM 10_1101-2021_01_07_425675 60 4 MS MS NNP 10_1101-2021_01_07_425675 60 5 127 127 CD 10_1101-2021_01_07_425675 60 6 spectra spectra NN 10_1101-2021_01_07_425675 60 7 supporting support VBG 10_1101-2021_01_07_425675 60 8 the the DT 10_1101-2021_01_07_425675 60 9 assigned assign VBN 10_1101-2021_01_07_425675 60 10 sequences sequence NNS 10_1101-2021_01_07_425675 60 11 of of IN 10_1101-2021_01_07_425675 60 12 the the DT 10_1101-2021_01_07_425675 60 13 Heavy Heavy NNP 10_1101-2021_01_07_425675 60 14 and and CC 10_1101-2021_01_07_425675 60 15 Light Light NNP 10_1101-2021_01_07_425675 60 16 Chain Chain NNP 10_1101-2021_01_07_425675 60 17 CDRs cdr NNS 10_1101-2021_01_07_425675 60 18 are be VBP 10_1101-2021_01_07_425675 60 19 shown show VBN 10_1101-2021_01_07_425675 60 20 below below IN 10_1101-2021_01_07_425675 60 21 the the DT 10_1101-2021_01_07_425675 60 22 128 128 CD 10_1101-2021_01_07_425675 60 23 alignments alignment NNS 10_1101-2021_01_07_425675 60 24 . . . 10_1101-2021_01_07_425675 61 1 Peptide peptide JJ 10_1101-2021_01_07_425675 61 2 sequence sequence NN 10_1101-2021_01_07_425675 61 3 and and CC 10_1101-2021_01_07_425675 61 4 fragment fragment NN 10_1101-2021_01_07_425675 61 5 coverage coverage NN 10_1101-2021_01_07_425675 61 6 are be VBP 10_1101-2021_01_07_425675 61 7 indicated indicate VBN 10_1101-2021_01_07_425675 61 8 on on IN 10_1101-2021_01_07_425675 61 9 top top NN 10_1101-2021_01_07_425675 61 10 of of IN 10_1101-2021_01_07_425675 61 11 the the DT 10_1101-2021_01_07_425675 61 12 spectra spectra NNP 10_1101-2021_01_07_425675 61 13 , , , 10_1101-2021_01_07_425675 61 14 with with IN 10_1101-2021_01_07_425675 61 15 b b NN 10_1101-2021_01_07_425675 61 16 / / SYM 10_1101-2021_01_07_425675 61 17 c c NNP 10_1101-2021_01_07_425675 61 18 ions ion NNS 10_1101-2021_01_07_425675 61 19 129 129 CD 10_1101-2021_01_07_425675 61 20 indicated indicate VBN 10_1101-2021_01_07_425675 61 21 in in IN 10_1101-2021_01_07_425675 61 22 blue blue NNP 10_1101-2021_01_07_425675 61 23 and and CC 10_1101-2021_01_07_425675 61 24 y y NNP 10_1101-2021_01_07_425675 61 25 / / SYM 10_1101-2021_01_07_425675 61 26 z z NNP 10_1101-2021_01_07_425675 61 27 ions ion NNS 10_1101-2021_01_07_425675 61 28 in in IN 10_1101-2021_01_07_425675 61 29 red red NN 10_1101-2021_01_07_425675 61 30 . . . 10_1101-2021_01_07_425675 62 1 The the DT 10_1101-2021_01_07_425675 62 2 same same JJ 10_1101-2021_01_07_425675 62 3 coloring coloring NN 10_1101-2021_01_07_425675 62 4 is be VBZ 10_1101-2021_01_07_425675 62 5 used use VBN 10_1101-2021_01_07_425675 62 6 to to TO 10_1101-2021_01_07_425675 62 7 annotate annotate VB 10_1101-2021_01_07_425675 62 8 peaks peak NNS 10_1101-2021_01_07_425675 62 9 in in IN 10_1101-2021_01_07_425675 62 10 the the DT 10_1101-2021_01_07_425675 62 11 spectra spectra NNP 10_1101-2021_01_07_425675 62 12 , , , 10_1101-2021_01_07_425675 62 13 with with IN 10_1101-2021_01_07_425675 62 14 130 130 CD 10_1101-2021_01_07_425675 62 15 additional additional JJ 10_1101-2021_01_07_425675 62 16 peaks peak NNS 10_1101-2021_01_07_425675 62 17 such such JJ 10_1101-2021_01_07_425675 62 18 as as IN 10_1101-2021_01_07_425675 62 19 intact intact JJ 10_1101-2021_01_07_425675 62 20 / / SYM 10_1101-2021_01_07_425675 62 21 charge charge VB 10_1101-2021_01_07_425675 62 22 reduced reduce VBN 10_1101-2021_01_07_425675 62 23 precursors precursor NNS 10_1101-2021_01_07_425675 62 24 , , , 10_1101-2021_01_07_425675 62 25 neutral neutral JJ 10_1101-2021_01_07_425675 62 26 losses loss NNS 10_1101-2021_01_07_425675 62 27 and and CC 10_1101-2021_01_07_425675 62 28 immonium immonium NN 10_1101-2021_01_07_425675 62 29 ions ion NNS 10_1101-2021_01_07_425675 62 30 indicated indicate VBN 10_1101-2021_01_07_425675 62 31 in in IN 10_1101-2021_01_07_425675 62 32 131 131 CD 10_1101-2021_01_07_425675 62 33 green green JJ 10_1101-2021_01_07_425675 62 34 . . . 10_1101-2021_01_07_425675 63 1 Note note VB 10_1101-2021_01_07_425675 63 2 that that DT 10_1101-2021_01_07_425675 63 3 to to TO 10_1101-2021_01_07_425675 63 4 prevent prevent VB 10_1101-2021_01_07_425675 63 5 overlapping overlap VBG 10_1101-2021_01_07_425675 63 6 peak peak NN 10_1101-2021_01_07_425675 63 7 labels label NNS 10_1101-2021_01_07_425675 63 8 , , , 10_1101-2021_01_07_425675 63 9 only only RB 10_1101-2021_01_07_425675 63 10 a a DT 10_1101-2021_01_07_425675 63 11 subset subset NN 10_1101-2021_01_07_425675 63 12 of of IN 10_1101-2021_01_07_425675 63 13 successfully successfully RB 10_1101-2021_01_07_425675 63 14 matched match VBN 10_1101-2021_01_07_425675 63 15 peaks peak NNS 10_1101-2021_01_07_425675 63 16 is be VBZ 10_1101-2021_01_07_425675 63 17 132 132 CD 10_1101-2021_01_07_425675 63 18 annotated annotate VBN 10_1101-2021_01_07_425675 63 19 . . . 10_1101-2021_01_07_425675 64 1 133 133 CD 10_1101-2021_01_07_425675 64 2 134 134 CD 10_1101-2021_01_07_425675 64 3 The the DT 10_1101-2021_01_07_425675 64 4 experimentally experimentally RB 10_1101-2021_01_07_425675 64 5 determined determine VBN 10_1101-2021_01_07_425675 64 6 de de NNP 10_1101-2021_01_07_425675 64 7 novo novo NNP 10_1101-2021_01_07_425675 64 8 sequence sequence NN 10_1101-2021_01_07_425675 64 9 is be VBZ 10_1101-2021_01_07_425675 64 10 shown show VBN 10_1101-2021_01_07_425675 64 11 alongside alongside IN 10_1101-2021_01_07_425675 64 12 the the DT 10_1101-2021_01_07_425675 64 13 known known JJ 10_1101-2021_01_07_425675 64 14 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 64 15 135 135 CD 10_1101-2021_01_07_425675 64 16 sequence sequence NN 10_1101-2021_01_07_425675 64 17 for for IN 10_1101-2021_01_07_425675 64 18 the the DT 10_1101-2021_01_07_425675 64 19 variable variable JJ 10_1101-2021_01_07_425675 64 20 domains domain NNS 10_1101-2021_01_07_425675 64 21 of of IN 10_1101-2021_01_07_425675 64 22 both both DT 10_1101-2021_01_07_425675 64 23 chains chain NNS 10_1101-2021_01_07_425675 64 24 in in IN 10_1101-2021_01_07_425675 64 25 Figure Figure NNP 10_1101-2021_01_07_425675 64 26 1 1 CD 10_1101-2021_01_07_425675 64 27 , , , 10_1101-2021_01_07_425675 64 28 with with IN 10_1101-2021_01_07_425675 64 29 exemplary exemplary JJ 10_1101-2021_01_07_425675 64 30 MS MS NNP 10_1101-2021_01_07_425675 64 31 / / SYM 10_1101-2021_01_07_425675 64 32 MS MS NNP 10_1101-2021_01_07_425675 64 33 spectra spectra NN 10_1101-2021_01_07_425675 64 34 for for IN 10_1101-2021_01_07_425675 64 35 136 136 CD 10_1101-2021_01_07_425675 64 36 the the DT 10_1101-2021_01_07_425675 64 37 CDRs cdr NNS 10_1101-2021_01_07_425675 64 38 . . . 10_1101-2021_01_07_425675 65 1 We -PRON- PRP 10_1101-2021_01_07_425675 65 2 achieved achieve VBD 10_1101-2021_01_07_425675 65 3 an an DT 10_1101-2021_01_07_425675 65 4 overall overall JJ 10_1101-2021_01_07_425675 65 5 sequence sequence NN 10_1101-2021_01_07_425675 65 6 accuracy accuracy NN 10_1101-2021_01_07_425675 65 7 of of IN 10_1101-2021_01_07_425675 65 8 99 99 CD 10_1101-2021_01_07_425675 65 9 % % NN 10_1101-2021_01_07_425675 65 10 with with IN 10_1101-2021_01_07_425675 65 11 the the DT 10_1101-2021_01_07_425675 65 12 automated automate VBN 10_1101-2021_01_07_425675 65 13 sequencing sequencing NN 10_1101-2021_01_07_425675 65 14 137 137 CD 10_1101-2021_01_07_425675 65 15 procedure procedure NN 10_1101-2021_01_07_425675 65 16 of of IN 10_1101-2021_01_07_425675 65 17 Supernovo Supernovo NNP 10_1101-2021_01_07_425675 65 18 , , , 10_1101-2021_01_07_425675 65 19 with with IN 10_1101-2021_01_07_425675 65 20 3 3 CD 10_1101-2021_01_07_425675 65 21 incorrect incorrect JJ 10_1101-2021_01_07_425675 65 22 assignments assignment NNS 10_1101-2021_01_07_425675 65 23 in in IN 10_1101-2021_01_07_425675 65 24 the the DT 10_1101-2021_01_07_425675 65 25 light light JJ 10_1101-2021_01_07_425675 65 26 chain chain NN 10_1101-2021_01_07_425675 65 27 . . . 10_1101-2021_01_07_425675 66 1 In in IN 10_1101-2021_01_07_425675 66 2 framework framework NN 10_1101-2021_01_07_425675 66 3 3 3 CD 10_1101-2021_01_07_425675 66 4 of of IN 10_1101-2021_01_07_425675 66 5 the the DT 10_1101-2021_01_07_425675 66 6 138 138 CD 10_1101-2021_01_07_425675 66 7 light light JJ 10_1101-2021_01_07_425675 66 8 chain chain NN 10_1101-2021_01_07_425675 66 9 , , , 10_1101-2021_01_07_425675 66 10 I75 I75 NNP 10_1101-2021_01_07_425675 66 11 was be VBD 10_1101-2021_01_07_425675 66 12 incorrectly incorrectly RB 10_1101-2021_01_07_425675 66 13 assigned assign VBN 10_1101-2021_01_07_425675 66 14 as as IN 10_1101-2021_01_07_425675 66 15 the the DT 10_1101-2021_01_07_425675 66 16 isomer isomer NN 10_1101-2021_01_07_425675 66 17 Leucine Leucine NNP 10_1101-2021_01_07_425675 66 18 ( ( -LRB- 10_1101-2021_01_07_425675 66 19 L L NNP 10_1101-2021_01_07_425675 66 20 ) ) -RRB- 10_1101-2021_01_07_425675 66 21 , , , 10_1101-2021_01_07_425675 66 22 a a DT 10_1101-2021_01_07_425675 66 23 common common JJ 10_1101-2021_01_07_425675 66 24 MS MS NNP 10_1101-2021_01_07_425675 66 25 - - HYPH 10_1101-2021_01_07_425675 66 26 based base VBN 10_1101-2021_01_07_425675 66 27 139 139 CD 10_1101-2021_01_07_425675 66 28 sequencing sequencing NN 10_1101-2021_01_07_425675 66 29 error error NN 10_1101-2021_01_07_425675 66 30 . . . 10_1101-2021_01_07_425675 67 1 In in IN 10_1101-2021_01_07_425675 67 2 CDRL3 cdrl3 NN 10_1101-2021_01_07_425675 67 3 of of IN 10_1101-2021_01_07_425675 67 4 the the DT 10_1101-2021_01_07_425675 67 5 light light JJ 10_1101-2021_01_07_425675 67 6 chain chain NN 10_1101-2021_01_07_425675 67 7 , , , 10_1101-2021_01_07_425675 67 8 an an DT 10_1101-2021_01_07_425675 67 9 additional additional JJ 10_1101-2021_01_07_425675 67 10 misassignment misassignment NN 10_1101-2021_01_07_425675 67 11 was be VBD 10_1101-2021_01_07_425675 67 12 made make VBN 10_1101-2021_01_07_425675 67 13 for for IN 10_1101-2021_01_07_425675 67 14 the the DT 10_1101-2021_01_07_425675 67 15 140 140 CD 10_1101-2021_01_07_425675 67 16 dipeptide dipeptide NN 10_1101-2021_01_07_425675 67 17 H91 H91 NNP 10_1101-2021_01_07_425675 67 18 / / SYM 10_1101-2021_01_07_425675 67 19 Y92 Y92 NNP 10_1101-2021_01_07_425675 67 20 , , , 10_1101-2021_01_07_425675 67 21 which which WDT 10_1101-2021_01_07_425675 67 22 was be VBD 10_1101-2021_01_07_425675 67 23 incorrectly incorrectly RB 10_1101-2021_01_07_425675 67 24 assigned assign VBN 10_1101-2021_01_07_425675 67 25 as as IN 10_1101-2021_01_07_425675 67 26 W91 W91 NNP 10_1101-2021_01_07_425675 67 27 / / SYM 10_1101-2021_01_07_425675 67 28 N92 N92 NNP 10_1101-2021_01_07_425675 67 29 . . . 10_1101-2021_01_07_425675 68 1 The the DT 10_1101-2021_01_07_425675 68 2 dipeptides dipeptide NNS 10_1101-2021_01_07_425675 68 3 HY HY NNP 10_1101-2021_01_07_425675 68 4 and and CC 10_1101-2021_01_07_425675 68 5 WN WN NNP 10_1101-2021_01_07_425675 68 6 141 141 CD 10_1101-2021_01_07_425675 68 7 have have VBP 10_1101-2021_01_07_425675 68 8 identical identical JJ 10_1101-2021_01_07_425675 68 9 masses masse NNS 10_1101-2021_01_07_425675 68 10 , , , 10_1101-2021_01_07_425675 68 11 and and CC 10_1101-2021_01_07_425675 68 12 the the DT 10_1101-2021_01_07_425675 68 13 misassignment misassignment NN 10_1101-2021_01_07_425675 68 14 of of IN 10_1101-2021_01_07_425675 68 15 W91 W91 NNP 10_1101-2021_01_07_425675 68 16 / / SYM 10_1101-2021_01_07_425675 68 17 N92 N92 NNP 10_1101-2021_01_07_425675 68 18 ( ( -LRB- 10_1101-2021_01_07_425675 68 19 especially especially RB 10_1101-2021_01_07_425675 68 20 W91 W91 NNP 10_1101-2021_01_07_425675 68 21 ) ) -RRB- 10_1101-2021_01_07_425675 68 22 was be VBD 10_1101-2021_01_07_425675 68 23 poorly poorly RB 10_1101-2021_01_07_425675 68 24 142 142 CD 10_1101-2021_01_07_425675 68 25 .CC .CC NFP 10_1101-2021_01_07_425675 68 26 - - : 10_1101-2021_01_07_425675 68 27 BY by IN 10_1101-2021_01_07_425675 68 28 4.0 4.0 CD 10_1101-2021_01_07_425675 68 29 International International NNP 10_1101-2021_01_07_425675 68 30 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 68 31 under under IN 10_1101-2021_01_07_425675 68 32 a a DT 10_1101-2021_01_07_425675 68 33 ( ( -LRB- 10_1101-2021_01_07_425675 68 34 which which WDT 10_1101-2021_01_07_425675 68 35 was be VBD 10_1101-2021_01_07_425675 68 36 not not RB 10_1101-2021_01_07_425675 68 37 certified certify VBN 10_1101-2021_01_07_425675 68 38 by by IN 10_1101-2021_01_07_425675 68 39 peer peer NN 10_1101-2021_01_07_425675 68 40 review review NN 10_1101-2021_01_07_425675 68 41 ) ) -RRB- 10_1101-2021_01_07_425675 68 42 is be VBZ 10_1101-2021_01_07_425675 68 43 the the DT 10_1101-2021_01_07_425675 68 44 author author NN 10_1101-2021_01_07_425675 68 45 / / SYM 10_1101-2021_01_07_425675 68 46 funder funder NN 10_1101-2021_01_07_425675 68 47 , , , 10_1101-2021_01_07_425675 68 48 who who WP 10_1101-2021_01_07_425675 68 49 has have VBZ 10_1101-2021_01_07_425675 68 50 granted grant VBN 10_1101-2021_01_07_425675 68 51 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 68 52 a a DT 10_1101-2021_01_07_425675 68 53 license license NN 10_1101-2021_01_07_425675 68 54 to to TO 10_1101-2021_01_07_425675 68 55 display display VB 10_1101-2021_01_07_425675 68 56 the the DT 10_1101-2021_01_07_425675 68 57 preprint preprint NN 10_1101-2021_01_07_425675 68 58 in in IN 10_1101-2021_01_07_425675 68 59 perpetuity perpetuity NN 10_1101-2021_01_07_425675 68 60 . . . 10_1101-2021_01_07_425675 69 1 It -PRON- PRP 10_1101-2021_01_07_425675 69 2 is be VBZ 10_1101-2021_01_07_425675 69 3 made make VBN 10_1101-2021_01_07_425675 69 4 The the DT 10_1101-2021_01_07_425675 69 5 copyright copyright NN 10_1101-2021_01_07_425675 69 6 holder holder NN 10_1101-2021_01_07_425675 69 7 for for IN 10_1101-2021_01_07_425675 69 8 this this DT 10_1101-2021_01_07_425675 69 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 69 10 version version NN 10_1101-2021_01_07_425675 69 11 posted post VBD 10_1101-2021_01_07_425675 69 12 January January NNP 10_1101-2021_01_07_425675 69 13 8 8 CD 10_1101-2021_01_07_425675 69 14 , , , 10_1101-2021_01_07_425675 69 15 2021 2021 CD 10_1101-2021_01_07_425675 69 16 . . . 10_1101-2021_01_07_425675 69 17 ; ; : 10_1101-2021_01_07_425675 69 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 69 19 : : : 10_1101-2021_01_07_425675 69 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 69 21 preprint preprint NN 10_1101-2021_01_07_425675 69 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 69 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 69 24 7 7 CD 10_1101-2021_01_07_425675 69 25 supported support VBN 10_1101-2021_01_07_425675 69 26 by by IN 10_1101-2021_01_07_425675 69 27 the the DT 10_1101-2021_01_07_425675 69 28 fragmentation fragmentation NN 10_1101-2021_01_07_425675 69 29 spectra spectra NNP 10_1101-2021_01_07_425675 69 30 , , , 10_1101-2021_01_07_425675 69 31 in in IN 10_1101-2021_01_07_425675 69 32 contrast contrast NN 10_1101-2021_01_07_425675 69 33 to to IN 10_1101-2021_01_07_425675 69 34 the the DT 10_1101-2021_01_07_425675 69 35 correct correct JJ 10_1101-2021_01_07_425675 69 36 H91 H91 NNP 10_1101-2021_01_07_425675 69 37 / / SYM 10_1101-2021_01_07_425675 69 38 Y92 Y92 NNP 10_1101-2021_01_07_425675 69 39 assignment assignment NN 10_1101-2021_01_07_425675 69 40 ( ( -LRB- 10_1101-2021_01_07_425675 69 41 see see VB 10_1101-2021_01_07_425675 69 42 c6 c6 NNP 10_1101-2021_01_07_425675 69 43 / / SYM 10_1101-2021_01_07_425675 69 44 c7 c7 NNP 10_1101-2021_01_07_425675 69 45 143 143 CD 10_1101-2021_01_07_425675 69 46 in in IN 10_1101-2021_01_07_425675 69 47 fragmentation fragmentation NN 10_1101-2021_01_07_425675 69 48 spectra spectra NN 10_1101-2021_01_07_425675 69 49 , , , 10_1101-2021_01_07_425675 69 50 Figure Figure NNP 10_1101-2021_01_07_425675 69 51 1 1 CD 10_1101-2021_01_07_425675 69 52 ) ) -RRB- 10_1101-2021_01_07_425675 69 53 . . . 10_1101-2021_01_07_425675 70 1 Overall overall RB 10_1101-2021_01_07_425675 70 2 , , , 10_1101-2021_01_07_425675 70 3 the the DT 10_1101-2021_01_07_425675 70 4 protocol protocol NN 10_1101-2021_01_07_425675 70 5 yielded yield VBD 10_1101-2021_01_07_425675 70 6 highly highly RB 10_1101-2021_01_07_425675 70 7 accurate accurate JJ 10_1101-2021_01_07_425675 70 8 sequences sequence NNS 10_1101-2021_01_07_425675 70 9 at at IN 10_1101-2021_01_07_425675 70 10 a a DT 10_1101-2021_01_07_425675 70 11 144 144 CD 10_1101-2021_01_07_425675 70 12 combined combine VBN 10_1101-2021_01_07_425675 70 13 230/233 230/233 JJ 10_1101-2021_01_07_425675 70 14 positions position NNS 10_1101-2021_01_07_425675 70 15 of of IN 10_1101-2021_01_07_425675 70 16 the the DT 10_1101-2021_01_07_425675 70 17 variable variable JJ 10_1101-2021_01_07_425675 70 18 domains domain NNS 10_1101-2021_01_07_425675 70 19 in in IN 10_1101-2021_01_07_425675 70 20 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 70 21 . . . 10_1101-2021_01_07_425675 71 1 145 145 CD 10_1101-2021_01_07_425675 71 2 146 146 CD 10_1101-2021_01_07_425675 71 3 147 147 CD 10_1101-2021_01_07_425675 71 4 Figure figure NN 10_1101-2021_01_07_425675 71 5 2 2 CD 10_1101-2021_01_07_425675 71 6 . . . 10_1101-2021_01_07_425675 72 1 Mass Mass NNP 10_1101-2021_01_07_425675 72 2 spectrometry spectrometry NNP 10_1101-2021_01_07_425675 72 3 based base VBN 10_1101-2021_01_07_425675 72 4 de de FW 10_1101-2021_01_07_425675 72 5 novo novo NNP 10_1101-2021_01_07_425675 72 6 sequence sequence NN 10_1101-2021_01_07_425675 72 7 of of IN 10_1101-2021_01_07_425675 72 8 the the DT 10_1101-2021_01_07_425675 72 9 mouse mouse NN 10_1101-2021_01_07_425675 72 10 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 72 11 anti anti JJ 10_1101-2021_01_07_425675 72 12 - - JJ 10_1101-2021_01_07_425675 72 13 FLAG FLAG NNP 10_1101-2021_01_07_425675 72 14 - - HYPH 10_1101-2021_01_07_425675 72 15 M2 M2 NNP 10_1101-2021_01_07_425675 72 16 antibody antibody NN 10_1101-2021_01_07_425675 72 17 . . . 10_1101-2021_01_07_425675 73 1 148 148 CD 10_1101-2021_01_07_425675 73 2 The the DT 10_1101-2021_01_07_425675 73 3 variable variable JJ 10_1101-2021_01_07_425675 73 4 regions region NNS 10_1101-2021_01_07_425675 73 5 of of IN 10_1101-2021_01_07_425675 73 6 the the DT 10_1101-2021_01_07_425675 73 7 Heavy heavy JJ 10_1101-2021_01_07_425675 73 8 ( ( -LRB- 10_1101-2021_01_07_425675 73 9 A a NN 10_1101-2021_01_07_425675 73 10 ) ) -RRB- 10_1101-2021_01_07_425675 73 11 and and CC 10_1101-2021_01_07_425675 73 12 Light Light NNP 10_1101-2021_01_07_425675 73 13 Chains Chains NNPS 10_1101-2021_01_07_425675 73 14 ( ( -LRB- 10_1101-2021_01_07_425675 73 15 B b NN 10_1101-2021_01_07_425675 73 16 ) ) -RRB- 10_1101-2021_01_07_425675 73 17 are be VBP 10_1101-2021_01_07_425675 73 18 shown show VBN 10_1101-2021_01_07_425675 73 19 . . . 10_1101-2021_01_07_425675 74 1 The the DT 10_1101-2021_01_07_425675 74 2 MS MS NNP 10_1101-2021_01_07_425675 74 3 - - HYPH 10_1101-2021_01_07_425675 74 4 based base VBN 10_1101-2021_01_07_425675 74 5 sequence sequence NN 10_1101-2021_01_07_425675 74 6 is be VBZ 10_1101-2021_01_07_425675 74 7 shown show VBN 10_1101-2021_01_07_425675 74 8 149 149 CD 10_1101-2021_01_07_425675 74 9 alongside alongside IN 10_1101-2021_01_07_425675 74 10 the the DT 10_1101-2021_01_07_425675 74 11 previously previously RB 10_1101-2021_01_07_425675 74 12 published publish VBN 10_1101-2021_01_07_425675 74 13 sequenced sequence VBN 10_1101-2021_01_07_425675 74 14 in in IN 10_1101-2021_01_07_425675 74 15 the the DT 10_1101-2021_01_07_425675 74 16 crystal crystal NN 10_1101-2021_01_07_425675 74 17 structure structure NN 10_1101-2021_01_07_425675 74 18 of of IN 10_1101-2021_01_07_425675 74 19 the the DT 10_1101-2021_01_07_425675 74 20 Fab Fab NNP 10_1101-2021_01_07_425675 74 21 ( ( -LRB- 10_1101-2021_01_07_425675 74 22 PDB PDB NNP 10_1101-2021_01_07_425675 74 23 ID ID NNP 10_1101-2021_01_07_425675 74 24 : : : 10_1101-2021_01_07_425675 74 25 2G60 2g60 LS 10_1101-2021_01_07_425675 74 26 ) ) -RRB- 10_1101-2021_01_07_425675 74 27 , , , 10_1101-2021_01_07_425675 74 28 and and CC 10_1101-2021_01_07_425675 74 29 150 150 CD 10_1101-2021_01_07_425675 74 30 germline germline NN 10_1101-2021_01_07_425675 74 31 sequence sequence NN 10_1101-2021_01_07_425675 74 32 ( ( -LRB- 10_1101-2021_01_07_425675 74 33 IMGT IMGT NNP 10_1101-2021_01_07_425675 74 34 - - HYPH 10_1101-2021_01_07_425675 74 35 DomainGapAlign domaingapalign NN 10_1101-2021_01_07_425675 74 36 ; ; : 10_1101-2021_01_07_425675 74 37 IGHV1 ighv1 LS 10_1101-2021_01_07_425675 74 38 - - HYPH 10_1101-2021_01_07_425675 74 39 04 04 CD 10_1101-2021_01_07_425675 74 40 / / SYM 10_1101-2021_01_07_425675 74 41 IGHJ2 IGHJ2 NNS 10_1101-2021_01_07_425675 74 42 ; ; : 10_1101-2021_01_07_425675 74 43 IGKV1 igkv1 CD 10_1101-2021_01_07_425675 74 44 - - SYM 10_1101-2021_01_07_425675 74 45 117 117 CD 10_1101-2021_01_07_425675 74 46 / / SYM 10_1101-2021_01_07_425675 74 47 IGKJ1 igkj1 NN 10_1101-2021_01_07_425675 74 48 ) ) -RRB- 10_1101-2021_01_07_425675 74 49 . . . 10_1101-2021_01_07_425675 75 1 Differential differential NN 10_1101-2021_01_07_425675 75 2 residues residue NNS 10_1101-2021_01_07_425675 75 3 151 151 CD 10_1101-2021_01_07_425675 75 4 are be VBP 10_1101-2021_01_07_425675 75 5 highlighted highlight VBN 10_1101-2021_01_07_425675 75 6 by by IN 10_1101-2021_01_07_425675 75 7 asterisks asterisk NNS 10_1101-2021_01_07_425675 75 8 ( ( -LRB- 10_1101-2021_01_07_425675 75 9 * * NFP 10_1101-2021_01_07_425675 75 10 ) ) -RRB- 10_1101-2021_01_07_425675 75 11 . . . 10_1101-2021_01_07_425675 76 1 Exemplary Exemplary NNP 10_1101-2021_01_07_425675 76 2 MS MS NNP 10_1101-2021_01_07_425675 76 3 / / SYM 10_1101-2021_01_07_425675 76 4 MS MS NNP 10_1101-2021_01_07_425675 76 5 spectra spectra NNP 10_1101-2021_01_07_425675 76 6 in in IN 10_1101-2021_01_07_425675 76 7 support support NN 10_1101-2021_01_07_425675 76 8 of of IN 10_1101-2021_01_07_425675 76 9 the the DT 10_1101-2021_01_07_425675 76 10 assigned assign VBN 10_1101-2021_01_07_425675 76 11 sequences sequence NNS 10_1101-2021_01_07_425675 76 12 are be VBP 10_1101-2021_01_07_425675 76 13 shown show VBN 10_1101-2021_01_07_425675 76 14 152 152 CD 10_1101-2021_01_07_425675 76 15 below below IN 10_1101-2021_01_07_425675 76 16 the the DT 10_1101-2021_01_07_425675 76 17 alignments alignment NNS 10_1101-2021_01_07_425675 76 18 . . . 10_1101-2021_01_07_425675 77 1 Peptide peptide JJ 10_1101-2021_01_07_425675 77 2 sequence sequence NN 10_1101-2021_01_07_425675 77 3 and and CC 10_1101-2021_01_07_425675 77 4 fragment fragment NN 10_1101-2021_01_07_425675 77 5 coverage coverage NN 10_1101-2021_01_07_425675 77 6 are be VBP 10_1101-2021_01_07_425675 77 7 indicated indicate VBN 10_1101-2021_01_07_425675 77 8 on on IN 10_1101-2021_01_07_425675 77 9 top top NN 10_1101-2021_01_07_425675 77 10 of of IN 10_1101-2021_01_07_425675 77 11 the the DT 10_1101-2021_01_07_425675 77 12 spectra spectra NNP 10_1101-2021_01_07_425675 77 13 , , , 10_1101-2021_01_07_425675 77 14 with with IN 10_1101-2021_01_07_425675 77 15 153 153 CD 10_1101-2021_01_07_425675 77 16 b b NN 10_1101-2021_01_07_425675 77 17 / / SYM 10_1101-2021_01_07_425675 77 18 c c NNP 10_1101-2021_01_07_425675 77 19 ions ion NNS 10_1101-2021_01_07_425675 77 20 indicated indicate VBN 10_1101-2021_01_07_425675 77 21 in in IN 10_1101-2021_01_07_425675 77 22 blue blue NNP 10_1101-2021_01_07_425675 77 23 , , , 10_1101-2021_01_07_425675 77 24 y y NNP 10_1101-2021_01_07_425675 77 25 / / SYM 10_1101-2021_01_07_425675 77 26 z z NNP 10_1101-2021_01_07_425675 77 27 ions ion NNS 10_1101-2021_01_07_425675 77 28 in in IN 10_1101-2021_01_07_425675 77 29 red red NN 10_1101-2021_01_07_425675 77 30 . . . 10_1101-2021_01_07_425675 78 1 The the DT 10_1101-2021_01_07_425675 78 2 same same JJ 10_1101-2021_01_07_425675 78 3 coloring coloring NN 10_1101-2021_01_07_425675 78 4 is be VBZ 10_1101-2021_01_07_425675 78 5 used use VBN 10_1101-2021_01_07_425675 78 6 to to TO 10_1101-2021_01_07_425675 78 7 annotate annotate VB 10_1101-2021_01_07_425675 78 8 peaks peak NNS 10_1101-2021_01_07_425675 78 9 in in IN 10_1101-2021_01_07_425675 78 10 the the DT 10_1101-2021_01_07_425675 78 11 spectra spectra NNP 10_1101-2021_01_07_425675 78 12 , , , 10_1101-2021_01_07_425675 78 13 with with IN 10_1101-2021_01_07_425675 78 14 154 154 CD 10_1101-2021_01_07_425675 78 15 additional additional JJ 10_1101-2021_01_07_425675 78 16 peaks peak NNS 10_1101-2021_01_07_425675 78 17 such such JJ 10_1101-2021_01_07_425675 78 18 as as IN 10_1101-2021_01_07_425675 78 19 intact intact JJ 10_1101-2021_01_07_425675 78 20 / / SYM 10_1101-2021_01_07_425675 78 21 charge charge VB 10_1101-2021_01_07_425675 78 22 reduced reduce VBN 10_1101-2021_01_07_425675 78 23 precursors precursor NNS 10_1101-2021_01_07_425675 78 24 , , , 10_1101-2021_01_07_425675 78 25 neutral neutral JJ 10_1101-2021_01_07_425675 78 26 losses loss NNS 10_1101-2021_01_07_425675 78 27 and and CC 10_1101-2021_01_07_425675 78 28 immonium immonium NN 10_1101-2021_01_07_425675 78 29 ions ion NNS 10_1101-2021_01_07_425675 78 30 indicated indicate VBN 10_1101-2021_01_07_425675 78 31 in in IN 10_1101-2021_01_07_425675 78 32 155 155 CD 10_1101-2021_01_07_425675 78 33 green green JJ 10_1101-2021_01_07_425675 78 34 . . . 10_1101-2021_01_07_425675 79 1 Note note VB 10_1101-2021_01_07_425675 79 2 that that DT 10_1101-2021_01_07_425675 79 3 to to TO 10_1101-2021_01_07_425675 79 4 prevent prevent VB 10_1101-2021_01_07_425675 79 5 overlapping overlap VBG 10_1101-2021_01_07_425675 79 6 peak peak NN 10_1101-2021_01_07_425675 79 7 labels label NNS 10_1101-2021_01_07_425675 79 8 , , , 10_1101-2021_01_07_425675 79 9 only only RB 10_1101-2021_01_07_425675 79 10 a a DT 10_1101-2021_01_07_425675 79 11 subset subset NN 10_1101-2021_01_07_425675 79 12 of of IN 10_1101-2021_01_07_425675 79 13 successfully successfully RB 10_1101-2021_01_07_425675 79 14 matched match VBN 10_1101-2021_01_07_425675 79 15 peaks peak NNS 10_1101-2021_01_07_425675 79 16 is be VBZ 10_1101-2021_01_07_425675 79 17 156 156 CD 10_1101-2021_01_07_425675 79 18 annotated annotate VBN 10_1101-2021_01_07_425675 79 19 . . . 10_1101-2021_01_07_425675 80 1 157 157 CD 10_1101-2021_01_07_425675 80 2 158 158 CD 10_1101-2021_01_07_425675 80 3 .CC .CC : 10_1101-2021_01_07_425675 80 4 - - : 10_1101-2021_01_07_425675 80 5 BY by IN 10_1101-2021_01_07_425675 80 6 4.0 4.0 CD 10_1101-2021_01_07_425675 80 7 International International NNP 10_1101-2021_01_07_425675 80 8 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 80 9 under under IN 10_1101-2021_01_07_425675 80 10 a a DT 10_1101-2021_01_07_425675 80 11 ( ( -LRB- 10_1101-2021_01_07_425675 80 12 which which WDT 10_1101-2021_01_07_425675 80 13 was be VBD 10_1101-2021_01_07_425675 80 14 not not RB 10_1101-2021_01_07_425675 80 15 certified certify VBN 10_1101-2021_01_07_425675 80 16 by by IN 10_1101-2021_01_07_425675 80 17 peer peer NN 10_1101-2021_01_07_425675 80 18 review review NN 10_1101-2021_01_07_425675 80 19 ) ) -RRB- 10_1101-2021_01_07_425675 80 20 is be VBZ 10_1101-2021_01_07_425675 80 21 the the DT 10_1101-2021_01_07_425675 80 22 author author NN 10_1101-2021_01_07_425675 80 23 / / SYM 10_1101-2021_01_07_425675 80 24 funder funder NN 10_1101-2021_01_07_425675 80 25 , , , 10_1101-2021_01_07_425675 80 26 who who WP 10_1101-2021_01_07_425675 80 27 has have VBZ 10_1101-2021_01_07_425675 80 28 granted grant VBN 10_1101-2021_01_07_425675 80 29 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 80 30 a a DT 10_1101-2021_01_07_425675 80 31 license license NN 10_1101-2021_01_07_425675 80 32 to to TO 10_1101-2021_01_07_425675 80 33 display display VB 10_1101-2021_01_07_425675 80 34 the the DT 10_1101-2021_01_07_425675 80 35 preprint preprint NN 10_1101-2021_01_07_425675 80 36 in in IN 10_1101-2021_01_07_425675 80 37 perpetuity perpetuity NN 10_1101-2021_01_07_425675 80 38 . . . 10_1101-2021_01_07_425675 81 1 It -PRON- PRP 10_1101-2021_01_07_425675 81 2 is be VBZ 10_1101-2021_01_07_425675 81 3 made make VBN 10_1101-2021_01_07_425675 81 4 The the DT 10_1101-2021_01_07_425675 81 5 copyright copyright NN 10_1101-2021_01_07_425675 81 6 holder holder NN 10_1101-2021_01_07_425675 81 7 for for IN 10_1101-2021_01_07_425675 81 8 this this DT 10_1101-2021_01_07_425675 81 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 81 10 version version NN 10_1101-2021_01_07_425675 81 11 posted post VBD 10_1101-2021_01_07_425675 81 12 January January NNP 10_1101-2021_01_07_425675 81 13 8 8 CD 10_1101-2021_01_07_425675 81 14 , , , 10_1101-2021_01_07_425675 81 15 2021 2021 CD 10_1101-2021_01_07_425675 81 16 . . . 10_1101-2021_01_07_425675 81 17 ; ; : 10_1101-2021_01_07_425675 81 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 81 19 : : : 10_1101-2021_01_07_425675 81 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 81 21 preprint preprint NN 10_1101-2021_01_07_425675 81 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 81 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 81 24 8 8 CD 10_1101-2021_01_07_425675 81 25 We -PRON- PRP 10_1101-2021_01_07_425675 81 26 next next RB 10_1101-2021_01_07_425675 81 27 applied apply VBD 10_1101-2021_01_07_425675 81 28 our -PRON- PRP$ 10_1101-2021_01_07_425675 81 29 sequencing sequence VBG 10_1101-2021_01_07_425675 81 30 protocol protocol NN 10_1101-2021_01_07_425675 81 31 to to IN 10_1101-2021_01_07_425675 81 32 the the DT 10_1101-2021_01_07_425675 81 33 mouse mouse NN 10_1101-2021_01_07_425675 81 34 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 81 35 anti anti JJ 10_1101-2021_01_07_425675 81 36 - - JJ 10_1101-2021_01_07_425675 81 37 FLAG FLAG NNP 10_1101-2021_01_07_425675 81 38 - - HYPH 10_1101-2021_01_07_425675 81 39 M2 M2 NNP 10_1101-2021_01_07_425675 81 40 antibody antibody NN 10_1101-2021_01_07_425675 81 41 as as IN 10_1101-2021_01_07_425675 81 42 a a DT 10_1101-2021_01_07_425675 81 43 159 159 CD 10_1101-2021_01_07_425675 81 44 test test NN 10_1101-2021_01_07_425675 81 45 case case NN 10_1101-2021_01_07_425675 81 46 24 24 CD 10_1101-2021_01_07_425675 81 47 . . . 10_1101-2021_01_07_425675 82 1 Despite despite IN 10_1101-2021_01_07_425675 82 2 the the DT 10_1101-2021_01_07_425675 82 3 widespread widespread JJ 10_1101-2021_01_07_425675 82 4 use use NN 10_1101-2021_01_07_425675 82 5 of of IN 10_1101-2021_01_07_425675 82 6 anti anti JJ 10_1101-2021_01_07_425675 82 7 - - JJ 10_1101-2021_01_07_425675 82 8 FLAG FLAG NNP 10_1101-2021_01_07_425675 82 9 - - HYPH 10_1101-2021_01_07_425675 82 10 M2 m2 NN 10_1101-2021_01_07_425675 82 11 to to TO 10_1101-2021_01_07_425675 82 12 detect detect VB 10_1101-2021_01_07_425675 82 13 and and CC 10_1101-2021_01_07_425675 82 14 purify purify VB 10_1101-2021_01_07_425675 82 15 FLAG FLAG NNP 10_1101-2021_01_07_425675 82 16 - - HYPH 10_1101-2021_01_07_425675 82 17 tagged tag VBN 10_1101-2021_01_07_425675 82 18 160 160 CD 10_1101-2021_01_07_425675 82 19 proteins protein NNS 10_1101-2021_01_07_425675 82 20 32 32 CD 10_1101-2021_01_07_425675 82 21 , , , 10_1101-2021_01_07_425675 82 22 the the DT 10_1101-2021_01_07_425675 82 23 only only JJ 10_1101-2021_01_07_425675 82 24 publicly publicly RB 10_1101-2021_01_07_425675 82 25 available available JJ 10_1101-2021_01_07_425675 82 26 sequences sequence NNS 10_1101-2021_01_07_425675 82 27 can can MD 10_1101-2021_01_07_425675 82 28 be be VB 10_1101-2021_01_07_425675 82 29 found find VBN 10_1101-2021_01_07_425675 82 30 in in IN 10_1101-2021_01_07_425675 82 31 the the DT 10_1101-2021_01_07_425675 82 32 crystal crystal NN 10_1101-2021_01_07_425675 82 33 structure structure NN 10_1101-2021_01_07_425675 82 34 of of IN 10_1101-2021_01_07_425675 82 35 the the DT 10_1101-2021_01_07_425675 82 36 Fab Fab NNP 10_1101-2021_01_07_425675 82 37 161 161 CD 10_1101-2021_01_07_425675 82 38 33 33 CD 10_1101-2021_01_07_425675 82 39 . . . 10_1101-2021_01_07_425675 83 1 The the DT 10_1101-2021_01_07_425675 83 2 modelled model VBN 10_1101-2021_01_07_425675 83 3 sequence sequence NN 10_1101-2021_01_07_425675 83 4 of of IN 10_1101-2021_01_07_425675 83 5 the the DT 10_1101-2021_01_07_425675 83 6 original original JJ 10_1101-2021_01_07_425675 83 7 crystal crystal NN 10_1101-2021_01_07_425675 83 8 structure structure NN 10_1101-2021_01_07_425675 83 9 had have VBD 10_1101-2021_01_07_425675 83 10 to to TO 10_1101-2021_01_07_425675 83 11 be be VB 10_1101-2021_01_07_425675 83 12 inferred infer VBN 10_1101-2021_01_07_425675 83 13 from from IN 10_1101-2021_01_07_425675 83 14 germline germline NN 10_1101-2021_01_07_425675 83 15 162 162 CD 10_1101-2021_01_07_425675 83 16 sequences sequence NNS 10_1101-2021_01_07_425675 83 17 that that WDT 10_1101-2021_01_07_425675 83 18 could could MD 10_1101-2021_01_07_425675 83 19 match match VB 10_1101-2021_01_07_425675 83 20 the the DT 10_1101-2021_01_07_425675 83 21 experimental experimental JJ 10_1101-2021_01_07_425675 83 22 electron electron NNP 10_1101-2021_01_07_425675 83 23 density density NN 10_1101-2021_01_07_425675 83 24 and and CC 10_1101-2021_01_07_425675 83 25 also also RB 10_1101-2021_01_07_425675 83 26 includes include VBZ 10_1101-2021_01_07_425675 83 27 many many JJ 10_1101-2021_01_07_425675 83 28 163 163 CD 10_1101-2021_01_07_425675 83 29 placeholder placeholder NN 10_1101-2021_01_07_425675 83 30 Alanines alanine NNS 10_1101-2021_01_07_425675 83 31 at at IN 10_1101-2021_01_07_425675 83 32 positions position NNS 10_1101-2021_01_07_425675 83 33 that that WDT 10_1101-2021_01_07_425675 83 34 could could MD 10_1101-2021_01_07_425675 83 35 not not RB 10_1101-2021_01_07_425675 83 36 be be VB 10_1101-2021_01_07_425675 83 37 straightforwardly straightforwardly RB 10_1101-2021_01_07_425675 83 38 interpreted interpret VBN 10_1101-2021_01_07_425675 83 39 . . . 10_1101-2021_01_07_425675 84 1 The the DT 10_1101-2021_01_07_425675 84 2 full full JJ 10_1101-2021_01_07_425675 84 3 anti-164 anti-164 NN 10_1101-2021_01_07_425675 84 4 FLAG FLAG NNP 10_1101-2021_01_07_425675 84 5 - - HYPH 10_1101-2021_01_07_425675 84 6 M2 M2 NNP 10_1101-2021_01_07_425675 84 7 dataset dataset NN 10_1101-2021_01_07_425675 84 8 from from IN 10_1101-2021_01_07_425675 84 9 the the DT 10_1101-2021_01_07_425675 84 10 9 9 CD 10_1101-2021_01_07_425675 84 11 proteases protease NNS 10_1101-2021_01_07_425675 84 12 included include VBD 10_1101-2021_01_07_425675 84 13 3371 3371 CD 10_1101-2021_01_07_425675 84 14 peptide peptide NN 10_1101-2021_01_07_425675 84 15 reads read NNS 10_1101-2021_01_07_425675 84 16 ( ( -LRB- 10_1101-2021_01_07_425675 84 17 with with IN 10_1101-2021_01_07_425675 84 18 scores score NNS 10_1101-2021_01_07_425675 84 19 > > NNP 10_1101-2021_01_07_425675 84 20 = = SYM 10_1101-2021_01_07_425675 84 21 500 500 CD 10_1101-2021_01_07_425675 84 22 ) ) -RRB- 10_1101-2021_01_07_425675 84 23 ; ; : 10_1101-2021_01_07_425675 84 24 1983 1983 CD 10_1101-2021_01_07_425675 84 25 165 165 CD 10_1101-2021_01_07_425675 84 26 with with IN 10_1101-2021_01_07_425675 84 27 superior superior JJ 10_1101-2021_01_07_425675 84 28 stepped step VBN 10_1101-2021_01_07_425675 84 29 HCD HCD NNP 10_1101-2021_01_07_425675 84 30 fragmentation fragmentation NN 10_1101-2021_01_07_425675 84 31 spectra spectra NNP 10_1101-2021_01_07_425675 84 32 , , , 10_1101-2021_01_07_425675 84 33 and and CC 10_1101-2021_01_07_425675 84 34 1388 1388 CD 10_1101-2021_01_07_425675 84 35 with with IN 10_1101-2021_01_07_425675 84 36 superior superior JJ 10_1101-2021_01_07_425675 84 37 EThcD EThcD NNP 10_1101-2021_01_07_425675 84 38 spectra spectra NNP 10_1101-2021_01_07_425675 84 39 . . . 10_1101-2021_01_07_425675 85 1 We -PRON- PRP 10_1101-2021_01_07_425675 85 2 166 166 CD 10_1101-2021_01_07_425675 85 3 achieved achieve VBD 10_1101-2021_01_07_425675 85 4 full full JJ 10_1101-2021_01_07_425675 85 5 sequence sequence NN 10_1101-2021_01_07_425675 85 6 coverage coverage NN 10_1101-2021_01_07_425675 85 7 of of IN 10_1101-2021_01_07_425675 85 8 the the DT 10_1101-2021_01_07_425675 85 9 variable variable JJ 10_1101-2021_01_07_425675 85 10 regions region NNS 10_1101-2021_01_07_425675 85 11 of of IN 10_1101-2021_01_07_425675 85 12 both both CC 10_1101-2021_01_07_425675 85 13 heavy heavy JJ 10_1101-2021_01_07_425675 85 14 and and CC 10_1101-2021_01_07_425675 85 15 light light JJ 10_1101-2021_01_07_425675 85 16 chains chain NNS 10_1101-2021_01_07_425675 85 17 , , , 10_1101-2021_01_07_425675 85 18 with with IN 10_1101-2021_01_07_425675 85 19 a a DT 10_1101-2021_01_07_425675 85 20 167 167 CD 10_1101-2021_01_07_425675 85 21 median median JJ 10_1101-2021_01_07_425675 85 22 depth depth NN 10_1101-2021_01_07_425675 85 23 of of IN 10_1101-2021_01_07_425675 85 24 coverage coverage NN 10_1101-2021_01_07_425675 85 25 in in IN 10_1101-2021_01_07_425675 85 26 the the DT 10_1101-2021_01_07_425675 85 27 CDRs cdr NNS 10_1101-2021_01_07_425675 85 28 ranging range VBG 10_1101-2021_01_07_425675 85 29 from from IN 10_1101-2021_01_07_425675 85 30 32 32 CD 10_1101-2021_01_07_425675 85 31 to to TO 10_1101-2021_01_07_425675 85 32 192 192 CD 10_1101-2021_01_07_425675 85 33 ( ( -LRB- 10_1101-2021_01_07_425675 85 34 see see VB 10_1101-2021_01_07_425675 85 35 Table table NN 10_1101-2021_01_07_425675 85 36 S1 s1 NN 10_1101-2021_01_07_425675 85 37 ) ) -RRB- 10_1101-2021_01_07_425675 85 38 . . . 10_1101-2021_01_07_425675 86 1 As as IN 10_1101-2021_01_07_425675 86 2 for for IN 10_1101-2021_01_07_425675 86 3 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 86 4 , , , 10_1101-2021_01_07_425675 86 5 168 168 CD 10_1101-2021_01_07_425675 86 6 the the DT 10_1101-2021_01_07_425675 86 7 depth depth NN 10_1101-2021_01_07_425675 86 8 of of IN 10_1101-2021_01_07_425675 86 9 coverage coverage NN 10_1101-2021_01_07_425675 86 10 was be VBD 10_1101-2021_01_07_425675 86 11 better well JJR 10_1101-2021_01_07_425675 86 12 in in IN 10_1101-2021_01_07_425675 86 13 the the DT 10_1101-2021_01_07_425675 86 14 light light JJ 10_1101-2021_01_07_425675 86 15 chain chain NN 10_1101-2021_01_07_425675 86 16 compared compare VBN 10_1101-2021_01_07_425675 86 17 to to IN 10_1101-2021_01_07_425675 86 18 the the DT 10_1101-2021_01_07_425675 86 19 heavy heavy JJ 10_1101-2021_01_07_425675 86 20 chain chain NN 10_1101-2021_01_07_425675 86 21 ( ( -LRB- 10_1101-2021_01_07_425675 86 22 see see VB 10_1101-2021_01_07_425675 86 23 Figure Figure NNP 10_1101-2021_01_07_425675 86 24 S1 S1 NNP 10_1101-2021_01_07_425675 86 25 - - : 10_1101-2021_01_07_425675 86 26 169 169 CD 10_1101-2021_01_07_425675 86 27 S2 s2 NN 10_1101-2021_01_07_425675 86 28 ) ) -RRB- 10_1101-2021_01_07_425675 86 29 . . . 10_1101-2021_01_07_425675 87 1 The the DT 10_1101-2021_01_07_425675 87 2 full full JJ 10_1101-2021_01_07_425675 87 3 MS MS NNP 10_1101-2021_01_07_425675 87 4 - - HYPH 10_1101-2021_01_07_425675 87 5 based base VBN 10_1101-2021_01_07_425675 87 6 anti anti JJ 10_1101-2021_01_07_425675 87 7 - - JJ 10_1101-2021_01_07_425675 87 8 FLAG FLAG NNP 10_1101-2021_01_07_425675 87 9 - - HYPH 10_1101-2021_01_07_425675 87 10 M2 m2 NN 10_1101-2021_01_07_425675 87 11 sequences sequence NNS 10_1101-2021_01_07_425675 87 12 can can MD 10_1101-2021_01_07_425675 87 13 be be VB 10_1101-2021_01_07_425675 87 14 found find VBN 10_1101-2021_01_07_425675 87 15 in in IN 10_1101-2021_01_07_425675 87 16 FASTA FASTA NNP 10_1101-2021_01_07_425675 87 17 format format NN 10_1101-2021_01_07_425675 87 18 in in IN 10_1101-2021_01_07_425675 87 19 the the DT 10_1101-2021_01_07_425675 87 20 170 170 CD 10_1101-2021_01_07_425675 87 21 supplementary supplementary JJ 10_1101-2021_01_07_425675 87 22 information information NN 10_1101-2021_01_07_425675 87 23 . . . 10_1101-2021_01_07_425675 88 1 171 171 CD 10_1101-2021_01_07_425675 88 2 172 172 CD 10_1101-2021_01_07_425675 88 3 173 173 CD 10_1101-2021_01_07_425675 88 4 Figure figure NN 10_1101-2021_01_07_425675 88 5 3 3 CD 10_1101-2021_01_07_425675 88 6 . . . 10_1101-2021_01_07_425675 89 1 Validation validation NN 10_1101-2021_01_07_425675 89 2 of of IN 10_1101-2021_01_07_425675 89 3 the the DT 10_1101-2021_01_07_425675 89 4 MS MS NNP 10_1101-2021_01_07_425675 89 5 - - HYPH 10_1101-2021_01_07_425675 89 6 based base VBN 10_1101-2021_01_07_425675 89 7 anti anti JJ 10_1101-2021_01_07_425675 89 8 - - JJ 10_1101-2021_01_07_425675 89 9 FLAG FLAG NNP 10_1101-2021_01_07_425675 89 10 - - HYPH 10_1101-2021_01_07_425675 89 11 M2 M2 NNP 10_1101-2021_01_07_425675 89 12 sequence sequence NN 10_1101-2021_01_07_425675 89 13 . . . 10_1101-2021_01_07_425675 90 1 A a LS 10_1101-2021_01_07_425675 90 2 ) ) -RRB- 10_1101-2021_01_07_425675 90 3 the the DT 10_1101-2021_01_07_425675 90 4 previously previously RB 10_1101-2021_01_07_425675 90 5 published publish VBN 10_1101-2021_01_07_425675 90 6 crystal crystal NN 10_1101-2021_01_07_425675 90 7 structure structure NN 10_1101-2021_01_07_425675 90 8 174 174 CD 10_1101-2021_01_07_425675 90 9 of of IN 10_1101-2021_01_07_425675 90 10 the the DT 10_1101-2021_01_07_425675 90 11 anti anti JJ 10_1101-2021_01_07_425675 90 12 - - JJ 10_1101-2021_01_07_425675 90 13 FLAG flag JJ 10_1101-2021_01_07_425675 90 14 - - HYPH 10_1101-2021_01_07_425675 90 15 M2 M2 NNP 10_1101-2021_01_07_425675 90 16 FAb FAb NNP 10_1101-2021_01_07_425675 90 17 was be VBD 10_1101-2021_01_07_425675 90 18 remodeled remodel VBN 10_1101-2021_01_07_425675 90 19 with with IN 10_1101-2021_01_07_425675 90 20 the the DT 10_1101-2021_01_07_425675 90 21 experimentally experimentally RB 10_1101-2021_01_07_425675 90 22 determined determine VBN 10_1101-2021_01_07_425675 90 23 sequence sequence NN 10_1101-2021_01_07_425675 90 24 , , , 10_1101-2021_01_07_425675 90 25 shown show VBN 10_1101-2021_01_07_425675 90 26 in in IN 10_1101-2021_01_07_425675 90 27 surface surface NN 10_1101-2021_01_07_425675 90 28 175 175 CD 10_1101-2021_01_07_425675 90 29 rendering render VBG 10_1101-2021_01_07_425675 90 30 with with IN 10_1101-2021_01_07_425675 90 31 CDRs cdr NNS 10_1101-2021_01_07_425675 90 32 and and CC 10_1101-2021_01_07_425675 90 33 differential differential NN 10_1101-2021_01_07_425675 90 34 residues residue NNS 10_1101-2021_01_07_425675 90 35 highlighted highlight VBN 10_1101-2021_01_07_425675 90 36 in in IN 10_1101-2021_01_07_425675 90 37 colors color NNS 10_1101-2021_01_07_425675 90 38 . . . 10_1101-2021_01_07_425675 91 1 B b NN 10_1101-2021_01_07_425675 91 2 ) ) -RRB- 10_1101-2021_01_07_425675 91 3 2Fo 2fo CD 10_1101-2021_01_07_425675 91 4 - - : 10_1101-2021_01_07_425675 91 5 Fc Fc NNP 10_1101-2021_01_07_425675 91 6 electron electron NN 10_1101-2021_01_07_425675 91 7 density density NN 10_1101-2021_01_07_425675 91 8 of of IN 10_1101-2021_01_07_425675 91 9 the the DT 10_1101-2021_01_07_425675 91 10 new new JJ 10_1101-2021_01_07_425675 91 11 176 176 CD 10_1101-2021_01_07_425675 91 12 refined refined JJ 10_1101-2021_01_07_425675 91 13 map map NN 10_1101-2021_01_07_425675 91 14 contoured contour VBD 10_1101-2021_01_07_425675 91 15 at at IN 10_1101-2021_01_07_425675 91 16 1 1 CD 10_1101-2021_01_07_425675 91 17 RMSD RMSD NNP 10_1101-2021_01_07_425675 91 18 is be VBZ 10_1101-2021_01_07_425675 91 19 shown show VBN 10_1101-2021_01_07_425675 91 20 in in IN 10_1101-2021_01_07_425675 91 21 blue blue JJ 10_1101-2021_01_07_425675 91 22 and and CC 10_1101-2021_01_07_425675 91 23 Fo Fo NNP 10_1101-2021_01_07_425675 91 24 - - HYPH 10_1101-2021_01_07_425675 91 25 Fc Fc NNP 10_1101-2021_01_07_425675 91 26 positive positive JJ 10_1101-2021_01_07_425675 91 27 difference difference NN 10_1101-2021_01_07_425675 91 28 density density NN 10_1101-2021_01_07_425675 91 29 of of IN 10_1101-2021_01_07_425675 91 30 the the DT 10_1101-2021_01_07_425675 91 31 original original JJ 10_1101-2021_01_07_425675 91 32 177 177 CD 10_1101-2021_01_07_425675 91 33 deposited deposit VBN 10_1101-2021_01_07_425675 91 34 map map NN 10_1101-2021_01_07_425675 91 35 contoured contour VBD 10_1101-2021_01_07_425675 91 36 at at IN 10_1101-2021_01_07_425675 91 37 1.7 1.7 CD 10_1101-2021_01_07_425675 91 38 RMSD RMSD NNP 10_1101-2021_01_07_425675 91 39 in in IN 10_1101-2021_01_07_425675 91 40 green green NN 10_1101-2021_01_07_425675 91 41 around around IN 10_1101-2021_01_07_425675 91 42 the the DT 10_1101-2021_01_07_425675 91 43 CDR cdr NN 10_1101-2021_01_07_425675 91 44 loops loop NNS 10_1101-2021_01_07_425675 91 45 of of IN 10_1101-2021_01_07_425675 91 46 the the DT 10_1101-2021_01_07_425675 91 47 heavy heavy JJ 10_1101-2021_01_07_425675 91 48 and and CC 10_1101-2021_01_07_425675 91 49 light light JJ 10_1101-2021_01_07_425675 91 50 chains chain NNS 10_1101-2021_01_07_425675 91 51 . . . 10_1101-2021_01_07_425675 92 1 178 178 CD 10_1101-2021_01_07_425675 92 2 Differential differential NN 10_1101-2021_01_07_425675 92 3 residues residue NNS 10_1101-2021_01_07_425675 92 4 between between IN 10_1101-2021_01_07_425675 92 5 the the DT 10_1101-2021_01_07_425675 92 6 published publish VBN 10_1101-2021_01_07_425675 92 7 crystal crystal NN 10_1101-2021_01_07_425675 92 8 structure structure NN 10_1101-2021_01_07_425675 92 9 and and CC 10_1101-2021_01_07_425675 92 10 the the DT 10_1101-2021_01_07_425675 92 11 model model NN 10_1101-2021_01_07_425675 92 12 based base VBN 10_1101-2021_01_07_425675 92 13 on on IN 10_1101-2021_01_07_425675 92 14 our -PRON- PRP$ 10_1101-2021_01_07_425675 92 15 antibody antibody NN 10_1101-2021_01_07_425675 92 16 179 179 CD 10_1101-2021_01_07_425675 92 17 sequencing sequencing NN 10_1101-2021_01_07_425675 92 18 are be VBP 10_1101-2021_01_07_425675 92 19 indicated indicate VBN 10_1101-2021_01_07_425675 92 20 in in IN 10_1101-2021_01_07_425675 92 21 purple purple NN 10_1101-2021_01_07_425675 92 22 . . . 10_1101-2021_01_07_425675 93 1 C C NNP 10_1101-2021_01_07_425675 93 2 ) ) -RRB- 10_1101-2021_01_07_425675 93 3 Western western JJ 10_1101-2021_01_07_425675 93 4 blot blot NN 10_1101-2021_01_07_425675 93 5 validation validation NN 10_1101-2021_01_07_425675 93 6 of of IN 10_1101-2021_01_07_425675 93 7 the the DT 10_1101-2021_01_07_425675 93 8 synthetic synthetic JJ 10_1101-2021_01_07_425675 93 9 recombinant recombinant JJ 10_1101-2021_01_07_425675 93 10 anti anti JJ 10_1101-2021_01_07_425675 93 11 - - JJ 10_1101-2021_01_07_425675 93 12 FLAG FLAG NNP 10_1101-2021_01_07_425675 93 13 - - HYPH 10_1101-2021_01_07_425675 93 14 M2 M2 NNP 10_1101-2021_01_07_425675 93 15 180 180 CD 10_1101-2021_01_07_425675 93 16 antibody antibody NN 10_1101-2021_01_07_425675 93 17 produced produce VBN 10_1101-2021_01_07_425675 93 18 with with IN 10_1101-2021_01_07_425675 93 19 the the DT 10_1101-2021_01_07_425675 93 20 experimentally experimentally RB 10_1101-2021_01_07_425675 93 21 determined determine VBN 10_1101-2021_01_07_425675 93 22 sequence sequence NN 10_1101-2021_01_07_425675 93 23 demonstrate demonstrate NN 10_1101-2021_01_07_425675 93 24 equivalent equivalent JJ 10_1101-2021_01_07_425675 93 25 FLAG flag NN 10_1101-2021_01_07_425675 93 26 - - HYPH 10_1101-2021_01_07_425675 93 27 tag tag NN 10_1101-2021_01_07_425675 93 28 binding bind VBG 10_1101-2021_01_07_425675 93 29 181 181 CD 10_1101-2021_01_07_425675 93 30 compared compare VBN 10_1101-2021_01_07_425675 93 31 to to IN 10_1101-2021_01_07_425675 93 32 commercial commercial JJ 10_1101-2021_01_07_425675 93 33 anti anti JJ 10_1101-2021_01_07_425675 93 34 - - JJ 10_1101-2021_01_07_425675 93 35 FLAG FLAG NNP 10_1101-2021_01_07_425675 93 36 - - HYPH 10_1101-2021_01_07_425675 93 37 M2 M2 NNP 10_1101-2021_01_07_425675 93 38 ( ( -LRB- 10_1101-2021_01_07_425675 93 39 see see VB 10_1101-2021_01_07_425675 93 40 also also RB 10_1101-2021_01_07_425675 93 41 Figure Figure NNP 10_1101-2021_01_07_425675 93 42 S3 S3 NNP 10_1101-2021_01_07_425675 93 43 ) ) -RRB- 10_1101-2021_01_07_425675 93 44 . . . 10_1101-2021_01_07_425675 94 1 182 182 CD 10_1101-2021_01_07_425675 94 2 183 183 CD 10_1101-2021_01_07_425675 94 3 .CC .CC , 10_1101-2021_01_07_425675 94 4 - - : 10_1101-2021_01_07_425675 94 5 BY by IN 10_1101-2021_01_07_425675 94 6 4.0 4.0 CD 10_1101-2021_01_07_425675 94 7 International International NNP 10_1101-2021_01_07_425675 94 8 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 94 9 under under IN 10_1101-2021_01_07_425675 94 10 a a DT 10_1101-2021_01_07_425675 94 11 ( ( -LRB- 10_1101-2021_01_07_425675 94 12 which which WDT 10_1101-2021_01_07_425675 94 13 was be VBD 10_1101-2021_01_07_425675 94 14 not not RB 10_1101-2021_01_07_425675 94 15 certified certify VBN 10_1101-2021_01_07_425675 94 16 by by IN 10_1101-2021_01_07_425675 94 17 peer peer NN 10_1101-2021_01_07_425675 94 18 review review NN 10_1101-2021_01_07_425675 94 19 ) ) -RRB- 10_1101-2021_01_07_425675 94 20 is be VBZ 10_1101-2021_01_07_425675 94 21 the the DT 10_1101-2021_01_07_425675 94 22 author author NN 10_1101-2021_01_07_425675 94 23 / / SYM 10_1101-2021_01_07_425675 94 24 funder funder NN 10_1101-2021_01_07_425675 94 25 , , , 10_1101-2021_01_07_425675 94 26 who who WP 10_1101-2021_01_07_425675 94 27 has have VBZ 10_1101-2021_01_07_425675 94 28 granted grant VBN 10_1101-2021_01_07_425675 94 29 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 94 30 a a DT 10_1101-2021_01_07_425675 94 31 license license NN 10_1101-2021_01_07_425675 94 32 to to TO 10_1101-2021_01_07_425675 94 33 display display VB 10_1101-2021_01_07_425675 94 34 the the DT 10_1101-2021_01_07_425675 94 35 preprint preprint NN 10_1101-2021_01_07_425675 94 36 in in IN 10_1101-2021_01_07_425675 94 37 perpetuity perpetuity NN 10_1101-2021_01_07_425675 94 38 . . . 10_1101-2021_01_07_425675 95 1 It -PRON- PRP 10_1101-2021_01_07_425675 95 2 is be VBZ 10_1101-2021_01_07_425675 95 3 made make VBN 10_1101-2021_01_07_425675 95 4 The the DT 10_1101-2021_01_07_425675 95 5 copyright copyright NN 10_1101-2021_01_07_425675 95 6 holder holder NN 10_1101-2021_01_07_425675 95 7 for for IN 10_1101-2021_01_07_425675 95 8 this this DT 10_1101-2021_01_07_425675 95 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 95 10 version version NN 10_1101-2021_01_07_425675 95 11 posted post VBD 10_1101-2021_01_07_425675 95 12 January January NNP 10_1101-2021_01_07_425675 95 13 8 8 CD 10_1101-2021_01_07_425675 95 14 , , , 10_1101-2021_01_07_425675 95 15 2021 2021 CD 10_1101-2021_01_07_425675 95 16 . . . 10_1101-2021_01_07_425675 95 17 ; ; : 10_1101-2021_01_07_425675 95 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 95 19 : : : 10_1101-2021_01_07_425675 95 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 95 21 preprint preprint NN 10_1101-2021_01_07_425675 95 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 95 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 95 24 9 9 CD 10_1101-2021_01_07_425675 95 25 The the DT 10_1101-2021_01_07_425675 95 26 MS MS NNP 10_1101-2021_01_07_425675 95 27 - - HYPH 10_1101-2021_01_07_425675 95 28 based base VBN 10_1101-2021_01_07_425675 95 29 sequences sequence NNS 10_1101-2021_01_07_425675 95 30 of of IN 10_1101-2021_01_07_425675 95 31 anti anti JJ 10_1101-2021_01_07_425675 95 32 - - JJ 10_1101-2021_01_07_425675 95 33 FLAG FLAG NNP 10_1101-2021_01_07_425675 95 34 - - HYPH 10_1101-2021_01_07_425675 95 35 M2 M2 NNP 10_1101-2021_01_07_425675 95 36 are be VBP 10_1101-2021_01_07_425675 95 37 shown show VBN 10_1101-2021_01_07_425675 95 38 alongside alongside IN 10_1101-2021_01_07_425675 95 39 the the DT 10_1101-2021_01_07_425675 95 40 crystal crystal NN 10_1101-2021_01_07_425675 95 41 structure structure NN 10_1101-2021_01_07_425675 95 42 sequences sequence VBZ 10_1101-2021_01_07_425675 95 43 184 184 CD 10_1101-2021_01_07_425675 95 44 and and CC 10_1101-2021_01_07_425675 95 45 the the DT 10_1101-2021_01_07_425675 95 46 inferred inferred JJ 10_1101-2021_01_07_425675 95 47 germline germline NN 10_1101-2021_01_07_425675 95 48 precursors precursor NNS 10_1101-2021_01_07_425675 95 49 with with IN 10_1101-2021_01_07_425675 95 50 exemplary exemplary JJ 10_1101-2021_01_07_425675 95 51 MS MS NNP 10_1101-2021_01_07_425675 95 52 / / SYM 10_1101-2021_01_07_425675 95 53 MS MS NNP 10_1101-2021_01_07_425675 95 54 spectra spectra NNP 10_1101-2021_01_07_425675 95 55 for for IN 10_1101-2021_01_07_425675 95 56 the the DT 10_1101-2021_01_07_425675 95 57 CDRs cdr NNS 10_1101-2021_01_07_425675 95 58 in in IN 10_1101-2021_01_07_425675 95 59 Figure Figure NNP 10_1101-2021_01_07_425675 95 60 2 2 CD 10_1101-2021_01_07_425675 95 61 . . . 10_1101-2021_01_07_425675 96 1 185 185 CD 10_1101-2021_01_07_425675 96 2 The the DT 10_1101-2021_01_07_425675 96 3 experimentally experimentally RB 10_1101-2021_01_07_425675 96 4 determined determine VBN 10_1101-2021_01_07_425675 96 5 sequence sequence NN 10_1101-2021_01_07_425675 96 6 reveals reveal VBZ 10_1101-2021_01_07_425675 96 7 that that IN 10_1101-2021_01_07_425675 96 8 anti anti JJ 10_1101-2021_01_07_425675 96 9 - - JJ 10_1101-2021_01_07_425675 96 10 FLAG FLAG NNP 10_1101-2021_01_07_425675 96 11 - - HYPH 10_1101-2021_01_07_425675 96 12 M2 M2 NNP 10_1101-2021_01_07_425675 96 13 is be VBZ 10_1101-2021_01_07_425675 96 14 a a DT 10_1101-2021_01_07_425675 96 15 mouse mouse NN 10_1101-2021_01_07_425675 96 16 IgG1 igg1 NN 10_1101-2021_01_07_425675 96 17 , , , 10_1101-2021_01_07_425675 96 18 with with IN 10_1101-2021_01_07_425675 96 19 an an DT 10_1101-2021_01_07_425675 96 20 186 186 CD 10_1101-2021_01_07_425675 96 21 IGHV1 ighv1 CD 10_1101-2021_01_07_425675 96 22 - - HYPH 10_1101-2021_01_07_425675 96 23 04 04 CD 10_1101-2021_01_07_425675 96 24 / / SYM 10_1101-2021_01_07_425675 96 25 IGHJ2 ighj2 NN 10_1101-2021_01_07_425675 96 26 heavy heavy JJ 10_1101-2021_01_07_425675 96 27 chain chain NN 10_1101-2021_01_07_425675 96 28 and and CC 10_1101-2021_01_07_425675 96 29 IGKV1 igkv1 CD 10_1101-2021_01_07_425675 96 30 - - SYM 10_1101-2021_01_07_425675 96 31 117 117 CD 10_1101-2021_01_07_425675 96 32 / / SYM 10_1101-2021_01_07_425675 96 33 IGKJ1 igkj1 NN 10_1101-2021_01_07_425675 96 34 kappa kappa NNP 10_1101-2021_01_07_425675 96 35 light light JJ 10_1101-2021_01_07_425675 96 36 chain chain NN 10_1101-2021_01_07_425675 96 37 . . . 10_1101-2021_01_07_425675 97 1 The the DT 10_1101-2021_01_07_425675 97 2 experimentally experimentally RB 10_1101-2021_01_07_425675 97 3 187 187 CD 10_1101-2021_01_07_425675 97 4 determined determine VBN 10_1101-2021_01_07_425675 97 5 sequence sequence NN 10_1101-2021_01_07_425675 97 6 differs differ NNS 10_1101-2021_01_07_425675 97 7 at at IN 10_1101-2021_01_07_425675 97 8 34 34 CD 10_1101-2021_01_07_425675 97 9 and and CC 10_1101-2021_01_07_425675 97 10 9 9 CD 10_1101-2021_01_07_425675 97 11 positions position NNS 10_1101-2021_01_07_425675 97 12 in in IN 10_1101-2021_01_07_425675 97 13 the the DT 10_1101-2021_01_07_425675 97 14 heavy heavy JJ 10_1101-2021_01_07_425675 97 15 and and CC 10_1101-2021_01_07_425675 97 16 light light JJ 10_1101-2021_01_07_425675 97 17 chain chain NN 10_1101-2021_01_07_425675 97 18 of of IN 10_1101-2021_01_07_425675 97 19 the the DT 10_1101-2021_01_07_425675 97 20 Fab Fab NNP 10_1101-2021_01_07_425675 97 21 crystal crystal NN 10_1101-2021_01_07_425675 97 22 188 188 CD 10_1101-2021_01_07_425675 97 23 structure structure NN 10_1101-2021_01_07_425675 97 24 , , , 10_1101-2021_01_07_425675 97 25 respectively respectively RB 10_1101-2021_01_07_425675 97 26 . . . 10_1101-2021_01_07_425675 98 1 To to TO 10_1101-2021_01_07_425675 98 2 validate validate VB 10_1101-2021_01_07_425675 98 3 the the DT 10_1101-2021_01_07_425675 98 4 experimentally experimentally RB 10_1101-2021_01_07_425675 98 5 determined determine VBN 10_1101-2021_01_07_425675 98 6 sequences sequence NNS 10_1101-2021_01_07_425675 98 7 , , , 10_1101-2021_01_07_425675 98 8 we -PRON- PRP 10_1101-2021_01_07_425675 98 9 remodeled remodel VBD 10_1101-2021_01_07_425675 98 10 the the DT 10_1101-2021_01_07_425675 98 11 189 189 CD 10_1101-2021_01_07_425675 98 12 crystal crystal NN 10_1101-2021_01_07_425675 98 13 structure structure NN 10_1101-2021_01_07_425675 98 14 using use VBG 10_1101-2021_01_07_425675 98 15 the the DT 10_1101-2021_01_07_425675 98 16 MS MS NNP 10_1101-2021_01_07_425675 98 17 - - HYPH 10_1101-2021_01_07_425675 98 18 based base VBN 10_1101-2021_01_07_425675 98 19 heavy heavy JJ 10_1101-2021_01_07_425675 98 20 and and CC 10_1101-2021_01_07_425675 98 21 light light JJ 10_1101-2021_01_07_425675 98 22 chains chain NNS 10_1101-2021_01_07_425675 98 23 , , , 10_1101-2021_01_07_425675 98 24 resulting result VBG 10_1101-2021_01_07_425675 98 25 in in IN 10_1101-2021_01_07_425675 98 26 much much JJ 10_1101-2021_01_07_425675 98 27 improved improve VBN 10_1101-2021_01_07_425675 98 28 model model NN 10_1101-2021_01_07_425675 98 29 190 190 CD 10_1101-2021_01_07_425675 98 30 statistics statistic NNS 10_1101-2021_01_07_425675 98 31 ( ( -LRB- 10_1101-2021_01_07_425675 98 32 see see VB 10_1101-2021_01_07_425675 98 33 Figure figure NN 10_1101-2021_01_07_425675 98 34 3 3 CD 10_1101-2021_01_07_425675 98 35 and and CC 10_1101-2021_01_07_425675 98 36 Table Table NNP 10_1101-2021_01_07_425675 98 37 S2 S2 NNP 10_1101-2021_01_07_425675 98 38 ) ) -RRB- 10_1101-2021_01_07_425675 98 39 . . . 10_1101-2021_01_07_425675 99 1 The the DT 10_1101-2021_01_07_425675 99 2 experimental experimental JJ 10_1101-2021_01_07_425675 99 3 electron electron NN 10_1101-2021_01_07_425675 99 4 densities density NNS 10_1101-2021_01_07_425675 99 5 show show VBP 10_1101-2021_01_07_425675 99 6 excellent excellent JJ 10_1101-2021_01_07_425675 99 7 support support NN 10_1101-2021_01_07_425675 99 8 191 191 CD 10_1101-2021_01_07_425675 99 9 of of IN 10_1101-2021_01_07_425675 99 10 the the DT 10_1101-2021_01_07_425675 99 11 MS MS NNP 10_1101-2021_01_07_425675 99 12 - - HYPH 10_1101-2021_01_07_425675 99 13 based base VBN 10_1101-2021_01_07_425675 99 14 sequence sequence NN 10_1101-2021_01_07_425675 99 15 ( ( -LRB- 10_1101-2021_01_07_425675 99 16 as as IN 10_1101-2021_01_07_425675 99 17 shown show VBN 10_1101-2021_01_07_425675 99 18 for for IN 10_1101-2021_01_07_425675 99 19 the the DT 10_1101-2021_01_07_425675 99 20 CDRs cdr NNS 10_1101-2021_01_07_425675 99 21 in in IN 10_1101-2021_01_07_425675 99 22 Figure Figure NNP 10_1101-2021_01_07_425675 99 23 3B 3b NN 10_1101-2021_01_07_425675 99 24 ) ) -RRB- 10_1101-2021_01_07_425675 99 25 . . . 10_1101-2021_01_07_425675 100 1 A a DT 10_1101-2021_01_07_425675 100 2 notable notable JJ 10_1101-2021_01_07_425675 100 3 exception exception NN 10_1101-2021_01_07_425675 100 4 is be VBZ 10_1101-2021_01_07_425675 100 5 L51 L51 NNP 10_1101-2021_01_07_425675 100 6 in in IN 10_1101-2021_01_07_425675 100 7 192 192 CD 10_1101-2021_01_07_425675 100 8 CDRH2 CDRH2 NNS 10_1101-2021_01_07_425675 100 9 of of IN 10_1101-2021_01_07_425675 100 10 the the DT 10_1101-2021_01_07_425675 100 11 heavy heavy JJ 10_1101-2021_01_07_425675 100 12 chain chain NN 10_1101-2021_01_07_425675 100 13 . . . 10_1101-2021_01_07_425675 101 1 The the DT 10_1101-2021_01_07_425675 101 2 MS MS NNP 10_1101-2021_01_07_425675 101 3 - - HYPH 10_1101-2021_01_07_425675 101 4 based base VBN 10_1101-2021_01_07_425675 101 5 sequence sequence NN 10_1101-2021_01_07_425675 101 6 was be VBD 10_1101-2021_01_07_425675 101 7 assigned assign VBN 10_1101-2021_01_07_425675 101 8 as as IN 10_1101-2021_01_07_425675 101 9 Leucine Leucine NNP 10_1101-2021_01_07_425675 101 10 , , , 10_1101-2021_01_07_425675 101 11 but but CC 10_1101-2021_01_07_425675 101 12 the the DT 10_1101-2021_01_07_425675 101 13 193 193 CD 10_1101-2021_01_07_425675 101 14 experimental experimental JJ 10_1101-2021_01_07_425675 101 15 electron electron NNP 10_1101-2021_01_07_425675 101 16 density density NN 10_1101-2021_01_07_425675 101 17 supports support VBZ 10_1101-2021_01_07_425675 101 18 assignment assignment NN 10_1101-2021_01_07_425675 101 19 of of IN 10_1101-2021_01_07_425675 101 20 the the DT 10_1101-2021_01_07_425675 101 21 isomer isomer NN 10_1101-2021_01_07_425675 101 22 Isoleucine Isoleucine NNP 10_1101-2021_01_07_425675 101 23 instead instead RB 10_1101-2021_01_07_425675 101 24 ( ( -LRB- 10_1101-2021_01_07_425675 101 25 see see VB 10_1101-2021_01_07_425675 101 26 Figure Figure NNP 10_1101-2021_01_07_425675 101 27 194 194 CD 10_1101-2021_01_07_425675 101 28 S3 S3 NNP 10_1101-2021_01_07_425675 101 29 ) ) -RRB- 10_1101-2021_01_07_425675 101 30 . . . 10_1101-2021_01_07_425675 102 1 In in IN 10_1101-2021_01_07_425675 102 2 contrast contrast NN 10_1101-2021_01_07_425675 102 3 to to IN 10_1101-2021_01_07_425675 102 4 the the DT 10_1101-2021_01_07_425675 102 5 original original JJ 10_1101-2021_01_07_425675 102 6 model model NN 10_1101-2021_01_07_425675 102 7 our -PRON- PRP$ 10_1101-2021_01_07_425675 102 8 new new JJ 10_1101-2021_01_07_425675 102 9 MS MS NNP 10_1101-2021_01_07_425675 102 10 - - HYPH 10_1101-2021_01_07_425675 102 11 based base VBN 10_1101-2021_01_07_425675 102 12 model model NN 10_1101-2021_01_07_425675 102 13 reveals reveal VBZ 10_1101-2021_01_07_425675 102 14 a a DT 10_1101-2021_01_07_425675 102 15 predominantly predominantly RB 10_1101-2021_01_07_425675 102 16 positively positively RB 10_1101-2021_01_07_425675 102 17 195 195 CD 10_1101-2021_01_07_425675 102 18 charged charge VBN 10_1101-2021_01_07_425675 102 19 paratope paratope NN 10_1101-2021_01_07_425675 102 20 ( ( -LRB- 10_1101-2021_01_07_425675 102 21 see see VB 10_1101-2021_01_07_425675 102 22 Figure Figure NNP 10_1101-2021_01_07_425675 102 23 S4 S4 NNP 10_1101-2021_01_07_425675 102 24 ) ) -RRB- 10_1101-2021_01_07_425675 102 25 , , , 10_1101-2021_01_07_425675 102 26 which which WDT 10_1101-2021_01_07_425675 102 27 potentially potentially RB 10_1101-2021_01_07_425675 102 28 complements complement VBZ 10_1101-2021_01_07_425675 102 29 the the DT 10_1101-2021_01_07_425675 102 30 -3 -3 NNP 10_1101-2021_01_07_425675 102 31 net net JJ 10_1101-2021_01_07_425675 102 32 charge charge NN 10_1101-2021_01_07_425675 102 33 of of IN 10_1101-2021_01_07_425675 102 34 the the DT 10_1101-2021_01_07_425675 102 35 FLAG FLAG NNP 10_1101-2021_01_07_425675 102 36 196 196 CD 10_1101-2021_01_07_425675 102 37 tag tag NN 10_1101-2021_01_07_425675 102 38 epitope epitope NN 10_1101-2021_01_07_425675 102 39 ( ( -LRB- 10_1101-2021_01_07_425675 102 40 DYKDDDDK DYKDDDDK NNP 10_1101-2021_01_07_425675 102 41 ) ) -RRB- 10_1101-2021_01_07_425675 102 42 to to TO 10_1101-2021_01_07_425675 102 43 mediate mediate VB 10_1101-2021_01_07_425675 102 44 binding binding NN 10_1101-2021_01_07_425675 102 45 . . . 10_1101-2021_01_07_425675 103 1 The the DT 10_1101-2021_01_07_425675 103 2 experimentally experimentally RB 10_1101-2021_01_07_425675 103 3 determined determine VBN 10_1101-2021_01_07_425675 103 4 anti anti JJ 10_1101-2021_01_07_425675 103 5 - - JJ 10_1101-2021_01_07_425675 103 6 FLAG FLAG NNP 10_1101-2021_01_07_425675 103 7 - - HYPH 10_1101-2021_01_07_425675 103 8 M2 M2 NNP 10_1101-2021_01_07_425675 103 9 197 197 CD 10_1101-2021_01_07_425675 103 10 sequence sequence NN 10_1101-2021_01_07_425675 103 11 , , , 10_1101-2021_01_07_425675 103 12 with with IN 10_1101-2021_01_07_425675 103 13 the the DT 10_1101-2021_01_07_425675 103 14 L51I l51i JJ 10_1101-2021_01_07_425675 103 15 correction correction NN 10_1101-2021_01_07_425675 103 16 , , , 10_1101-2021_01_07_425675 103 17 was be VBD 10_1101-2021_01_07_425675 103 18 further further RB 10_1101-2021_01_07_425675 103 19 validated validate VBN 10_1101-2021_01_07_425675 103 20 by by IN 10_1101-2021_01_07_425675 103 21 testing test VBG 10_1101-2021_01_07_425675 103 22 binding binding NN 10_1101-2021_01_07_425675 103 23 of of IN 10_1101-2021_01_07_425675 103 24 the the DT 10_1101-2021_01_07_425675 103 25 synthetic synthetic JJ 10_1101-2021_01_07_425675 103 26 198 198 CD 10_1101-2021_01_07_425675 103 27 recombinant recombinant JJ 10_1101-2021_01_07_425675 103 28 antibody antibody NN 10_1101-2021_01_07_425675 103 29 to to IN 10_1101-2021_01_07_425675 103 30 a a DT 10_1101-2021_01_07_425675 103 31 purified purify VBN 10_1101-2021_01_07_425675 103 32 FLAG FLAG NNP 10_1101-2021_01_07_425675 103 33 - - HYPH 10_1101-2021_01_07_425675 103 34 tagged tag VBN 10_1101-2021_01_07_425675 103 35 protein protein NN 10_1101-2021_01_07_425675 103 36 in in IN 10_1101-2021_01_07_425675 103 37 Western western JJ 10_1101-2021_01_07_425675 103 38 blot blot NN 10_1101-2021_01_07_425675 103 39 analysis analysis NN 10_1101-2021_01_07_425675 103 40 ( ( -LRB- 10_1101-2021_01_07_425675 103 41 see see VB 10_1101-2021_01_07_425675 103 42 Figure Figure NNP 10_1101-2021_01_07_425675 103 43 3C 3c NN 10_1101-2021_01_07_425675 103 44 199 199 CD 10_1101-2021_01_07_425675 103 45 and and CC 10_1101-2021_01_07_425675 103 46 S5 S5 NNP 10_1101-2021_01_07_425675 103 47 ) ) -RRB- 10_1101-2021_01_07_425675 103 48 . . . 10_1101-2021_01_07_425675 104 1 The the DT 10_1101-2021_01_07_425675 104 2 synthetic synthetic JJ 10_1101-2021_01_07_425675 104 3 recombinant recombinant JJ 10_1101-2021_01_07_425675 104 4 antibody antibody NN 10_1101-2021_01_07_425675 104 5 showed show VBD 10_1101-2021_01_07_425675 104 6 equivalent equivalent JJ 10_1101-2021_01_07_425675 104 7 binding binding NN 10_1101-2021_01_07_425675 104 8 compared compare VBN 10_1101-2021_01_07_425675 104 9 to to IN 10_1101-2021_01_07_425675 104 10 the the DT 10_1101-2021_01_07_425675 104 11 original original JJ 10_1101-2021_01_07_425675 104 12 200 200 CD 10_1101-2021_01_07_425675 104 13 antibody antibody NN 10_1101-2021_01_07_425675 104 14 sample sample NN 10_1101-2021_01_07_425675 104 15 used use VBN 10_1101-2021_01_07_425675 104 16 for for IN 10_1101-2021_01_07_425675 104 17 sequencing sequencing NN 10_1101-2021_01_07_425675 104 18 , , , 10_1101-2021_01_07_425675 104 19 confirming confirm VBG 10_1101-2021_01_07_425675 104 20 that that IN 10_1101-2021_01_07_425675 104 21 the the DT 10_1101-2021_01_07_425675 104 22 experimentally experimentally RB 10_1101-2021_01_07_425675 104 23 determined determine VBN 10_1101-2021_01_07_425675 104 24 sequence sequence NN 10_1101-2021_01_07_425675 104 25 201 201 CD 10_1101-2021_01_07_425675 104 26 is be VBZ 10_1101-2021_01_07_425675 104 27 reliable reliable JJ 10_1101-2021_01_07_425675 104 28 to to TO 10_1101-2021_01_07_425675 104 29 obtain obtain VB 10_1101-2021_01_07_425675 104 30 the the DT 10_1101-2021_01_07_425675 104 31 recombinant recombinant JJ 10_1101-2021_01_07_425675 104 32 antibody antibody NN 10_1101-2021_01_07_425675 104 33 product product NN 10_1101-2021_01_07_425675 104 34 with with IN 10_1101-2021_01_07_425675 104 35 the the DT 10_1101-2021_01_07_425675 104 36 desired desire VBN 10_1101-2021_01_07_425675 104 37 functional functional JJ 10_1101-2021_01_07_425675 104 38 profile profile NN 10_1101-2021_01_07_425675 104 39 . . . 10_1101-2021_01_07_425675 105 1 202 202 CD 10_1101-2021_01_07_425675 105 2 203 203 CD 10_1101-2021_01_07_425675 105 3 Discussion discussion NN 10_1101-2021_01_07_425675 105 4 204 204 CD 10_1101-2021_01_07_425675 105 5 There there EX 10_1101-2021_01_07_425675 105 6 are be VBP 10_1101-2021_01_07_425675 105 7 four four CD 10_1101-2021_01_07_425675 105 8 other other JJ 10_1101-2021_01_07_425675 105 9 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 105 10 antibody antibody NN 10_1101-2021_01_07_425675 105 11 sequences sequence NNS 10_1101-2021_01_07_425675 105 12 against against IN 10_1101-2021_01_07_425675 105 13 the the DT 10_1101-2021_01_07_425675 105 14 FLAG FLAG NNP 10_1101-2021_01_07_425675 105 15 tag tag NN 10_1101-2021_01_07_425675 105 16 publicly publicly RB 10_1101-2021_01_07_425675 105 17 available available JJ 10_1101-2021_01_07_425675 105 18 205 205 CD 10_1101-2021_01_07_425675 105 19 through through IN 10_1101-2021_01_07_425675 105 20 the the DT 10_1101-2021_01_07_425675 105 21 ABCD ABCD NNP 10_1101-2021_01_07_425675 105 22 ( ( -LRB- 10_1101-2021_01_07_425675 105 23 AntiBodies AntiBodies NNP 10_1101-2021_01_07_425675 105 24 Chemically chemically RB 10_1101-2021_01_07_425675 105 25 Defined define VBN 10_1101-2021_01_07_425675 105 26 ) ) -RRB- 10_1101-2021_01_07_425675 105 27 database database NN 10_1101-2021_01_07_425675 105 28 34 34 CD 10_1101-2021_01_07_425675 105 29 - - SYM 10_1101-2021_01_07_425675 105 30 36 36 CD 10_1101-2021_01_07_425675 105 31 . . . 10_1101-2021_01_07_425675 106 1 Comparison comparison NN 10_1101-2021_01_07_425675 106 2 of of IN 10_1101-2021_01_07_425675 106 3 the the DT 10_1101-2021_01_07_425675 106 4 CDRs cdr NNS 10_1101-2021_01_07_425675 106 5 of of IN 10_1101-2021_01_07_425675 106 6 206 206 CD 10_1101-2021_01_07_425675 106 7 anti anti JJ 10_1101-2021_01_07_425675 106 8 - - JJ 10_1101-2021_01_07_425675 106 9 FLAG flag JJ 10_1101-2021_01_07_425675 106 10 - - HYPH 10_1101-2021_01_07_425675 106 11 M2 M2 NNP 10_1101-2021_01_07_425675 106 12 with with IN 10_1101-2021_01_07_425675 106 13 these these DT 10_1101-2021_01_07_425675 106 14 additional additional JJ 10_1101-2021_01_07_425675 106 15 four four CD 10_1101-2021_01_07_425675 106 16 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 106 17 antibodies antibody NNS 10_1101-2021_01_07_425675 106 18 reveals reveal VBZ 10_1101-2021_01_07_425675 106 19 a a DT 10_1101-2021_01_07_425675 106 20 few few JJ 10_1101-2021_01_07_425675 106 21 common common JJ 10_1101-2021_01_07_425675 106 22 motifs motif NNS 10_1101-2021_01_07_425675 106 23 that that IN 10_1101-2021_01_07_425675 106 24 207 207 CD 10_1101-2021_01_07_425675 106 25 may may MD 10_1101-2021_01_07_425675 106 26 determine determine VB 10_1101-2021_01_07_425675 106 27 FLAG FLAG NNP 10_1101-2021_01_07_425675 106 28 - - HYPH 10_1101-2021_01_07_425675 106 29 tag tag NN 10_1101-2021_01_07_425675 106 30 binding binding NN 10_1101-2021_01_07_425675 106 31 specificity specificity NN 10_1101-2021_01_07_425675 106 32 ( ( -LRB- 10_1101-2021_01_07_425675 106 33 see see VB 10_1101-2021_01_07_425675 106 34 Table Table NNP 10_1101-2021_01_07_425675 106 35 S3 S3 NNP 10_1101-2021_01_07_425675 106 36 ) ) -RRB- 10_1101-2021_01_07_425675 106 37 . . . 10_1101-2021_01_07_425675 107 1 In in IN 10_1101-2021_01_07_425675 107 2 the the DT 10_1101-2021_01_07_425675 107 3 heavy heavy JJ 10_1101-2021_01_07_425675 107 4 chain chain NN 10_1101-2021_01_07_425675 107 5 , , , 10_1101-2021_01_07_425675 107 6 the the DT 10_1101-2021_01_07_425675 107 7 only only JJ 10_1101-2021_01_07_425675 107 8 common common JJ 10_1101-2021_01_07_425675 107 9 208 208 CD 10_1101-2021_01_07_425675 107 10 motif motif NN 10_1101-2021_01_07_425675 107 11 between between IN 10_1101-2021_01_07_425675 107 12 all all DT 10_1101-2021_01_07_425675 107 13 five five CD 10_1101-2021_01_07_425675 107 14 monoclonals monoclonal NNS 10_1101-2021_01_07_425675 107 15 is be VBZ 10_1101-2021_01_07_425675 107 16 that that IN 10_1101-2021_01_07_425675 107 17 the the DT 10_1101-2021_01_07_425675 107 18 first first JJ 10_1101-2021_01_07_425675 107 19 three three CD 10_1101-2021_01_07_425675 107 20 residues residue NNS 10_1101-2021_01_07_425675 107 21 of of IN 10_1101-2021_01_07_425675 107 22 CDRH1 cdrh1 NN 10_1101-2021_01_07_425675 107 23 follow follow VB 10_1101-2021_01_07_425675 107 24 a a DT 10_1101-2021_01_07_425675 107 25 GXS GXS NNP 10_1101-2021_01_07_425675 107 26 209 209 CD 10_1101-2021_01_07_425675 107 27 sequence sequence NN 10_1101-2021_01_07_425675 107 28 . . . 10_1101-2021_01_07_425675 108 1 In in IN 10_1101-2021_01_07_425675 108 2 addition addition NN 10_1101-2021_01_07_425675 108 3 , , , 10_1101-2021_01_07_425675 108 4 the the DT 10_1101-2021_01_07_425675 108 5 last last JJ 10_1101-2021_01_07_425675 108 6 three three CD 10_1101-2021_01_07_425675 108 7 residues residue NNS 10_1101-2021_01_07_425675 108 8 of of IN 10_1101-2021_01_07_425675 108 9 CDRH3 CDRH3 NNS 10_1101-2021_01_07_425675 108 10 of of IN 10_1101-2021_01_07_425675 108 11 anti anti JJ 10_1101-2021_01_07_425675 108 12 - - JJ 10_1101-2021_01_07_425675 108 13 FLAG FLAG NNP 10_1101-2021_01_07_425675 108 14 - - HYPH 10_1101-2021_01_07_425675 108 15 M2 M2 NNP 10_1101-2021_01_07_425675 108 16 are be VBP 10_1101-2021_01_07_425675 108 17 YDY YDY NNP 10_1101-2021_01_07_425675 108 18 , , , 10_1101-2021_01_07_425675 108 19 similar similar JJ 10_1101-2021_01_07_425675 108 20 to to IN 10_1101-2021_01_07_425675 108 21 210 210 CD 10_1101-2021_01_07_425675 108 22 MDY MDY NNP 10_1101-2021_01_07_425675 108 23 in in IN 10_1101-2021_01_07_425675 108 24 H28 H28 NNP 10_1101-2021_01_07_425675 108 25 , , , 10_1101-2021_01_07_425675 108 26 and and CC 10_1101-2021_01_07_425675 108 27 YDF YDF NNP 10_1101-2021_01_07_425675 108 28 in in IN 10_1101-2021_01_07_425675 108 29 EEh13.6 EEh13.6 NNP 10_1101-2021_01_07_425675 108 30 ( ( -LRB- 10_1101-2021_01_07_425675 108 31 and and CC 10_1101-2021_01_07_425675 108 32 EEh14.3 EEh14.3 NNP 10_1101-2021_01_07_425675 108 33 also also RB 10_1101-2021_01_07_425675 108 34 ends end VBZ 10_1101-2021_01_07_425675 108 35 CDRH3 CDRH3 NNS 10_1101-2021_01_07_425675 108 36 with with IN 10_1101-2021_01_07_425675 108 37 an an DT 10_1101-2021_01_07_425675 108 38 aromatic aromatic JJ 10_1101-2021_01_07_425675 108 39 F F NNP 10_1101-2021_01_07_425675 108 40 residue residue NN 10_1101-2021_01_07_425675 108 41 ) ) -RRB- 10_1101-2021_01_07_425675 108 42 . . . 10_1101-2021_01_07_425675 109 1 211 211 CD 10_1101-2021_01_07_425675 109 2 In in IN 10_1101-2021_01_07_425675 109 3 contrast contrast NN 10_1101-2021_01_07_425675 109 4 to to IN 10_1101-2021_01_07_425675 109 5 the the DT 10_1101-2021_01_07_425675 109 6 heavy heavy JJ 10_1101-2021_01_07_425675 109 7 chain chain NN 10_1101-2021_01_07_425675 109 8 , , , 10_1101-2021_01_07_425675 109 9 the the DT 10_1101-2021_01_07_425675 109 10 CDRs cdr NNS 10_1101-2021_01_07_425675 109 11 of of IN 10_1101-2021_01_07_425675 109 12 the the DT 10_1101-2021_01_07_425675 109 13 light light JJ 10_1101-2021_01_07_425675 109 14 chain chain NN 10_1101-2021_01_07_425675 109 15 are be VBP 10_1101-2021_01_07_425675 109 16 almost almost RB 10_1101-2021_01_07_425675 109 17 completely completely RB 10_1101-2021_01_07_425675 109 18 conserved conserve VBN 10_1101-2021_01_07_425675 109 19 in in IN 10_1101-2021_01_07_425675 109 20 212 212 CD 10_1101-2021_01_07_425675 109 21 4/5 4/5 CD 10_1101-2021_01_07_425675 109 22 monoclonals monoclonal NNS 10_1101-2021_01_07_425675 109 23 with with IN 10_1101-2021_01_07_425675 109 24 only only RB 10_1101-2021_01_07_425675 109 25 minimal minimal JJ 10_1101-2021_01_07_425675 109 26 differences difference NNS 10_1101-2021_01_07_425675 109 27 compared compare VBN 10_1101-2021_01_07_425675 109 28 to to IN 10_1101-2021_01_07_425675 109 29 germline germline NN 10_1101-2021_01_07_425675 109 30 . . . 10_1101-2021_01_07_425675 110 1 The the DT 10_1101-2021_01_07_425675 110 2 anti anti JJ 10_1101-2021_01_07_425675 110 3 - - JJ 10_1101-2021_01_07_425675 110 4 FLAG FLAG NNP 10_1101-2021_01_07_425675 110 5 - - HYPH 10_1101-2021_01_07_425675 110 6 M2 M2 NNP 10_1101-2021_01_07_425675 110 7 and and CC 10_1101-2021_01_07_425675 110 8 H28 H28 NNP 10_1101-2021_01_07_425675 110 9 213 213 CD 10_1101-2021_01_07_425675 110 10 monoclonals monoclonal NNS 10_1101-2021_01_07_425675 110 11 were be VBD 10_1101-2021_01_07_425675 110 12 specifically specifically RB 10_1101-2021_01_07_425675 110 13 raised raise VBN 10_1101-2021_01_07_425675 110 14 in in IN 10_1101-2021_01_07_425675 110 15 mice mouse NNS 10_1101-2021_01_07_425675 110 16 against against IN 10_1101-2021_01_07_425675 110 17 the the DT 10_1101-2021_01_07_425675 110 18 FLAG FLAG NNP 10_1101-2021_01_07_425675 110 19 - - HYPH 10_1101-2021_01_07_425675 110 20 tag tag NN 10_1101-2021_01_07_425675 110 21 epitope epitope NN 10_1101-2021_01_07_425675 110 22 24 24 CD 10_1101-2021_01_07_425675 110 23 , , , 10_1101-2021_01_07_425675 110 24 35 35 CD 10_1101-2021_01_07_425675 110 25 , , , 10_1101-2021_01_07_425675 110 26 whereas whereas IN 10_1101-2021_01_07_425675 110 27 the the DT 10_1101-2021_01_07_425675 110 28 214 214 CD 10_1101-2021_01_07_425675 110 29 computationally computationally RB 10_1101-2021_01_07_425675 110 30 designed design VBN 10_1101-2021_01_07_425675 110 31 EEh13.6 eeh13.6 JJ 10_1101-2021_01_07_425675 110 32 and and CC 10_1101-2021_01_07_425675 110 33 EEh14.3 eeh14.3 JJ 10_1101-2021_01_07_425675 110 34 monoclonals monoclonal NNS 10_1101-2021_01_07_425675 110 35 contain contain VBP 10_1101-2021_01_07_425675 110 36 the the DT 10_1101-2021_01_07_425675 110 37 same same JJ 10_1101-2021_01_07_425675 110 38 light light JJ 10_1101-2021_01_07_425675 110 39 chain chain NN 10_1101-2021_01_07_425675 110 40 from from IN 10_1101-2021_01_07_425675 110 41 215 215 CD 10_1101-2021_01_07_425675 110 42 an an DT 10_1101-2021_01_07_425675 110 43 EE ee NN 10_1101-2021_01_07_425675 110 44 - - HYPH 10_1101-2021_01_07_425675 110 45 dipeptide dipeptide NN 10_1101-2021_01_07_425675 110 46 tag tag NN 10_1101-2021_01_07_425675 110 47 directed direct VBN 10_1101-2021_01_07_425675 110 48 antibody antibody NN 10_1101-2021_01_07_425675 110 49 34 34 CD 10_1101-2021_01_07_425675 110 50 . . . 10_1101-2021_01_07_425675 111 1 This this DT 10_1101-2021_01_07_425675 111 2 suggests suggest VBZ 10_1101-2021_01_07_425675 111 3 that that IN 10_1101-2021_01_07_425675 111 4 the the DT 10_1101-2021_01_07_425675 111 5 IGKV1 igkv1 CD 10_1101-2021_01_07_425675 111 6 - - SYM 10_1101-2021_01_07_425675 111 7 117 117 CD 10_1101-2021_01_07_425675 111 8 / / SYM 10_1101-2021_01_07_425675 111 9 IGKJ1 igkj1 NN 10_1101-2021_01_07_425675 111 10 light light JJ 10_1101-2021_01_07_425675 111 11 chain chain NN 10_1101-2021_01_07_425675 111 12 may may MD 10_1101-2021_01_07_425675 111 13 216 216 CD 10_1101-2021_01_07_425675 111 14 .CC .CC : 10_1101-2021_01_07_425675 111 15 - - : 10_1101-2021_01_07_425675 111 16 BY by IN 10_1101-2021_01_07_425675 111 17 4.0 4.0 CD 10_1101-2021_01_07_425675 111 18 International International NNP 10_1101-2021_01_07_425675 111 19 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 111 20 under under IN 10_1101-2021_01_07_425675 111 21 a a DT 10_1101-2021_01_07_425675 111 22 ( ( -LRB- 10_1101-2021_01_07_425675 111 23 which which WDT 10_1101-2021_01_07_425675 111 24 was be VBD 10_1101-2021_01_07_425675 111 25 not not RB 10_1101-2021_01_07_425675 111 26 certified certify VBN 10_1101-2021_01_07_425675 111 27 by by IN 10_1101-2021_01_07_425675 111 28 peer peer NN 10_1101-2021_01_07_425675 111 29 review review NN 10_1101-2021_01_07_425675 111 30 ) ) -RRB- 10_1101-2021_01_07_425675 111 31 is be VBZ 10_1101-2021_01_07_425675 111 32 the the DT 10_1101-2021_01_07_425675 111 33 author author NN 10_1101-2021_01_07_425675 111 34 / / SYM 10_1101-2021_01_07_425675 111 35 funder funder NN 10_1101-2021_01_07_425675 111 36 , , , 10_1101-2021_01_07_425675 111 37 who who WP 10_1101-2021_01_07_425675 111 38 has have VBZ 10_1101-2021_01_07_425675 111 39 granted grant VBN 10_1101-2021_01_07_425675 111 40 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 111 41 a a DT 10_1101-2021_01_07_425675 111 42 license license NN 10_1101-2021_01_07_425675 111 43 to to TO 10_1101-2021_01_07_425675 111 44 display display VB 10_1101-2021_01_07_425675 111 45 the the DT 10_1101-2021_01_07_425675 111 46 preprint preprint NN 10_1101-2021_01_07_425675 111 47 in in IN 10_1101-2021_01_07_425675 111 48 perpetuity perpetuity NN 10_1101-2021_01_07_425675 111 49 . . . 10_1101-2021_01_07_425675 112 1 It -PRON- PRP 10_1101-2021_01_07_425675 112 2 is be VBZ 10_1101-2021_01_07_425675 112 3 made make VBN 10_1101-2021_01_07_425675 112 4 The the DT 10_1101-2021_01_07_425675 112 5 copyright copyright NN 10_1101-2021_01_07_425675 112 6 holder holder NN 10_1101-2021_01_07_425675 112 7 for for IN 10_1101-2021_01_07_425675 112 8 this this DT 10_1101-2021_01_07_425675 112 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 112 10 version version NN 10_1101-2021_01_07_425675 112 11 posted post VBD 10_1101-2021_01_07_425675 112 12 January January NNP 10_1101-2021_01_07_425675 112 13 8 8 CD 10_1101-2021_01_07_425675 112 14 , , , 10_1101-2021_01_07_425675 112 15 2021 2021 CD 10_1101-2021_01_07_425675 112 16 . . . 10_1101-2021_01_07_425675 112 17 ; ; : 10_1101-2021_01_07_425675 112 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 112 19 : : : 10_1101-2021_01_07_425675 112 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 112 21 preprint preprint NN 10_1101-2021_01_07_425675 112 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 112 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 112 24 10 10 CD 10_1101-2021_01_07_425675 112 25 be be VBP 10_1101-2021_01_07_425675 112 26 a a DT 10_1101-2021_01_07_425675 112 27 common common JJ 10_1101-2021_01_07_425675 112 28 determinant determinant NN 10_1101-2021_01_07_425675 112 29 of of IN 10_1101-2021_01_07_425675 112 30 binding bind VBG 10_1101-2021_01_07_425675 112 31 to to IN 10_1101-2021_01_07_425675 112 32 a a DT 10_1101-2021_01_07_425675 112 33 small small JJ 10_1101-2021_01_07_425675 112 34 negatively negatively RB 10_1101-2021_01_07_425675 112 35 charged charge VBN 10_1101-2021_01_07_425675 112 36 peptide peptide NN 10_1101-2021_01_07_425675 112 37 epitope epitope NN 10_1101-2021_01_07_425675 112 38 like like IN 10_1101-2021_01_07_425675 112 39 the the DT 10_1101-2021_01_07_425675 112 40 FLAG-217 flag-217 JJ 10_1101-2021_01_07_425675 112 41 tag tag NN 10_1101-2021_01_07_425675 112 42 and and CC 10_1101-2021_01_07_425675 112 43 is be VBZ 10_1101-2021_01_07_425675 112 44 readily readily RB 10_1101-2021_01_07_425675 112 45 available available JJ 10_1101-2021_01_07_425675 112 46 as as IN 10_1101-2021_01_07_425675 112 47 a a DT 10_1101-2021_01_07_425675 112 48 hardcoded hardcode VBN 10_1101-2021_01_07_425675 112 49 germline germline NN 10_1101-2021_01_07_425675 112 50 sequence sequence NN 10_1101-2021_01_07_425675 112 51 in in IN 10_1101-2021_01_07_425675 112 52 the the DT 10_1101-2021_01_07_425675 112 53 mouse mouse NN 10_1101-2021_01_07_425675 112 54 antibody antibody NN 10_1101-2021_01_07_425675 112 55 repertoire repertoire NNP 10_1101-2021_01_07_425675 112 56 . . . 10_1101-2021_01_07_425675 113 1 218 218 CD 10_1101-2021_01_07_425675 113 2 The the DT 10_1101-2021_01_07_425675 113 3 availability availability NN 10_1101-2021_01_07_425675 113 4 of of IN 10_1101-2021_01_07_425675 113 5 the the DT 10_1101-2021_01_07_425675 113 6 anti anti JJ 10_1101-2021_01_07_425675 113 7 - - JJ 10_1101-2021_01_07_425675 113 8 FLAG FLAG NNP 10_1101-2021_01_07_425675 113 9 - - HYPH 10_1101-2021_01_07_425675 113 10 M2 M2 NNP 10_1101-2021_01_07_425675 113 11 sequences sequence NNS 10_1101-2021_01_07_425675 113 12 may may MD 10_1101-2021_01_07_425675 113 13 contribute contribute VB 10_1101-2021_01_07_425675 113 14 to to IN 10_1101-2021_01_07_425675 113 15 the the DT 10_1101-2021_01_07_425675 113 16 wider wide JJR 10_1101-2021_01_07_425675 113 17 use use NN 10_1101-2021_01_07_425675 113 18 of of IN 10_1101-2021_01_07_425675 113 19 this this DT 10_1101-2021_01_07_425675 113 20 important important JJ 10_1101-2021_01_07_425675 113 21 219 219 CD 10_1101-2021_01_07_425675 113 22 research research NN 10_1101-2021_01_07_425675 113 23 tool tool NN 10_1101-2021_01_07_425675 113 24 , , , 10_1101-2021_01_07_425675 113 25 as as RB 10_1101-2021_01_07_425675 113 26 well well RB 10_1101-2021_01_07_425675 113 27 as as IN 10_1101-2021_01_07_425675 113 28 the the DT 10_1101-2021_01_07_425675 113 29 development development NN 10_1101-2021_01_07_425675 113 30 and and CC 10_1101-2021_01_07_425675 113 31 engineering engineering NN 10_1101-2021_01_07_425675 113 32 of of IN 10_1101-2021_01_07_425675 113 33 better well JJR 10_1101-2021_01_07_425675 113 34 FLAG flag NN 10_1101-2021_01_07_425675 113 35 - - HYPH 10_1101-2021_01_07_425675 113 36 tag tag NN 10_1101-2021_01_07_425675 113 37 directed direct VBN 10_1101-2021_01_07_425675 113 38 antibodies antibody NNS 10_1101-2021_01_07_425675 113 39 . . . 10_1101-2021_01_07_425675 114 1 220 220 CD 10_1101-2021_01_07_425675 114 2 This this DT 10_1101-2021_01_07_425675 114 3 example example NN 10_1101-2021_01_07_425675 114 4 illustrates illustrate VBZ 10_1101-2021_01_07_425675 114 5 that that IN 10_1101-2021_01_07_425675 114 6 our -PRON- PRP$ 10_1101-2021_01_07_425675 114 7 MS MS NNP 10_1101-2021_01_07_425675 114 8 - - HYPH 10_1101-2021_01_07_425675 114 9 based base VBN 10_1101-2021_01_07_425675 114 10 sequencing sequence VBG 10_1101-2021_01_07_425675 114 11 protocol protocol NN 10_1101-2021_01_07_425675 114 12 yields yield NNS 10_1101-2021_01_07_425675 114 13 robust robust JJ 10_1101-2021_01_07_425675 114 14 and and CC 10_1101-2021_01_07_425675 114 15 reliable reliable JJ 10_1101-2021_01_07_425675 114 16 221 221 CD 10_1101-2021_01_07_425675 114 17 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 114 18 antibody antibody NN 10_1101-2021_01_07_425675 114 19 sequences sequence NNS 10_1101-2021_01_07_425675 114 20 . . . 10_1101-2021_01_07_425675 115 1 The the DT 10_1101-2021_01_07_425675 115 2 protocol protocol NN 10_1101-2021_01_07_425675 115 3 described describe VBN 10_1101-2021_01_07_425675 115 4 here here RB 10_1101-2021_01_07_425675 115 5 also also RB 10_1101-2021_01_07_425675 115 6 formed form VBD 10_1101-2021_01_07_425675 115 7 the the DT 10_1101-2021_01_07_425675 115 8 basis basis NN 10_1101-2021_01_07_425675 115 9 of of IN 10_1101-2021_01_07_425675 115 10 a a DT 10_1101-2021_01_07_425675 115 11 recent recent JJ 10_1101-2021_01_07_425675 115 12 222 222 CD 10_1101-2021_01_07_425675 115 13 application application NN 10_1101-2021_01_07_425675 115 14 where where WRB 10_1101-2021_01_07_425675 115 15 we -PRON- PRP 10_1101-2021_01_07_425675 115 16 sequenced sequence VBD 10_1101-2021_01_07_425675 115 17 an an DT 10_1101-2021_01_07_425675 115 18 antibody antibody NN 10_1101-2021_01_07_425675 115 19 directly directly RB 10_1101-2021_01_07_425675 115 20 from from IN 10_1101-2021_01_07_425675 115 21 patient patient NN 10_1101-2021_01_07_425675 115 22 - - HYPH 10_1101-2021_01_07_425675 115 23 derived derive VBN 10_1101-2021_01_07_425675 115 24 serum serum NN 10_1101-2021_01_07_425675 115 25 , , , 10_1101-2021_01_07_425675 115 26 using use VBG 10_1101-2021_01_07_425675 115 27 a a DT 10_1101-2021_01_07_425675 115 28 223 223 CD 10_1101-2021_01_07_425675 115 29 combination combination NN 10_1101-2021_01_07_425675 115 30 with with IN 10_1101-2021_01_07_425675 115 31 top top RB 10_1101-2021_01_07_425675 115 32 - - HYPH 10_1101-2021_01_07_425675 115 33 down down RP 10_1101-2021_01_07_425675 115 34 fragmentation fragmentation NN 10_1101-2021_01_07_425675 115 35 of of IN 10_1101-2021_01_07_425675 115 36 the the DT 10_1101-2021_01_07_425675 115 37 isolated isolate VBN 10_1101-2021_01_07_425675 115 38 Fab Fab NNP 10_1101-2021_01_07_425675 115 39 fragment fragment NN 10_1101-2021_01_07_425675 115 40 37 37 CD 10_1101-2021_01_07_425675 115 41 . . . 10_1101-2021_01_07_425675 116 1 The the DT 10_1101-2021_01_07_425675 116 2 dual dual JJ 10_1101-2021_01_07_425675 116 3 fragmentation fragmentation NN 10_1101-2021_01_07_425675 116 4 224 224 CD 10_1101-2021_01_07_425675 116 5 strategy strategy NN 10_1101-2021_01_07_425675 116 6 yields yield NNS 10_1101-2021_01_07_425675 116 7 high high JJ 10_1101-2021_01_07_425675 116 8 - - HYPH 10_1101-2021_01_07_425675 116 9 quality quality NN 10_1101-2021_01_07_425675 116 10 spectra spectra NN 10_1101-2021_01_07_425675 116 11 suitable suitable JJ 10_1101-2021_01_07_425675 116 12 for for IN 10_1101-2021_01_07_425675 116 13 de de FW 10_1101-2021_01_07_425675 116 14 novo novo NNP 10_1101-2021_01_07_425675 116 15 sequencing sequencing NNP 10_1101-2021_01_07_425675 116 16 and and CC 10_1101-2021_01_07_425675 116 17 may may MD 10_1101-2021_01_07_425675 116 18 further further RB 10_1101-2021_01_07_425675 116 19 contribute contribute VB 10_1101-2021_01_07_425675 116 20 to to IN 10_1101-2021_01_07_425675 116 21 225 225 CD 10_1101-2021_01_07_425675 116 22 the the DT 10_1101-2021_01_07_425675 116 23 exciting exciting JJ 10_1101-2021_01_07_425675 116 24 prospect prospect NN 10_1101-2021_01_07_425675 116 25 of of IN 10_1101-2021_01_07_425675 116 26 a a DT 10_1101-2021_01_07_425675 116 27 new new JJ 10_1101-2021_01_07_425675 116 28 era era NN 10_1101-2021_01_07_425675 116 29 of of IN 10_1101-2021_01_07_425675 116 30 serology serology NN 10_1101-2021_01_07_425675 116 31 in in IN 10_1101-2021_01_07_425675 116 32 which which WDT 10_1101-2021_01_07_425675 116 33 antibody antibody NN 10_1101-2021_01_07_425675 116 34 sequences sequence NNS 10_1101-2021_01_07_425675 116 35 can can MD 10_1101-2021_01_07_425675 116 36 be be VB 10_1101-2021_01_07_425675 116 37 directly directly RB 10_1101-2021_01_07_425675 116 38 226 226 CD 10_1101-2021_01_07_425675 116 39 obtained obtain VBN 10_1101-2021_01_07_425675 116 40 from from IN 10_1101-2021_01_07_425675 116 41 bodily bodily NNP 10_1101-2021_01_07_425675 116 42 fluids fluid NNS 10_1101-2021_01_07_425675 116 43 . . . 10_1101-2021_01_07_425675 117 1 227 227 CD 10_1101-2021_01_07_425675 117 2 228 228 CD 10_1101-2021_01_07_425675 117 3 229 229 CD 10_1101-2021_01_07_425675 117 4 Methods method NNS 10_1101-2021_01_07_425675 117 5 230 230 CD 10_1101-2021_01_07_425675 117 6 Sample sample NN 10_1101-2021_01_07_425675 117 7 preparation preparation NN 10_1101-2021_01_07_425675 117 8 231 231 CD 10_1101-2021_01_07_425675 117 9 Anti Anti NNP 10_1101-2021_01_07_425675 117 10 - - NNP 10_1101-2021_01_07_425675 117 11 Flag Flag NNP 10_1101-2021_01_07_425675 117 12 M2 M2 NNP 10_1101-2021_01_07_425675 117 13 antibody antibody NN 10_1101-2021_01_07_425675 117 14 was be VBD 10_1101-2021_01_07_425675 117 15 purchased purchase VBN 10_1101-2021_01_07_425675 117 16 from from IN 10_1101-2021_01_07_425675 117 17 Sigma Sigma NNP 10_1101-2021_01_07_425675 117 18 ( ( -LRB- 10_1101-2021_01_07_425675 117 19 catalogue catalogue NN 10_1101-2021_01_07_425675 117 20 number number NN 10_1101-2021_01_07_425675 117 21 F1804 F1804 NNP 10_1101-2021_01_07_425675 117 22 ) ) -RRB- 10_1101-2021_01_07_425675 117 23 . . . 10_1101-2021_01_07_425675 118 1 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 118 2 was be VBD 10_1101-2021_01_07_425675 118 3 232 232 CD 10_1101-2021_01_07_425675 118 4 provided provide VBN 10_1101-2021_01_07_425675 118 5 by by IN 10_1101-2021_01_07_425675 118 6 Roche Roche NNP 10_1101-2021_01_07_425675 118 7 ( ( -LRB- 10_1101-2021_01_07_425675 118 8 Penzberg Penzberg NNP 10_1101-2021_01_07_425675 118 9 , , , 10_1101-2021_01_07_425675 118 10 Germany Germany NNP 10_1101-2021_01_07_425675 118 11 ) ) -RRB- 10_1101-2021_01_07_425675 118 12 . . . 10_1101-2021_01_07_425675 119 1 27 27 CD 10_1101-2021_01_07_425675 119 2 μg μg DT 10_1101-2021_01_07_425675 119 3 of of IN 10_1101-2021_01_07_425675 119 4 each each DT 10_1101-2021_01_07_425675 119 5 sample sample NN 10_1101-2021_01_07_425675 119 6 was be VBD 10_1101-2021_01_07_425675 119 7 denatured denature VBN 10_1101-2021_01_07_425675 119 8 in in IN 10_1101-2021_01_07_425675 119 9 2 2 CD 10_1101-2021_01_07_425675 119 10 % % NN 10_1101-2021_01_07_425675 119 11 sodium sodium NN 10_1101-2021_01_07_425675 119 12 233 233 CD 10_1101-2021_01_07_425675 119 13 deoxycholate deoxycholate NN 10_1101-2021_01_07_425675 119 14 ( ( -LRB- 10_1101-2021_01_07_425675 119 15 SDC SDC NNP 10_1101-2021_01_07_425675 119 16 ) ) -RRB- 10_1101-2021_01_07_425675 119 17 , , , 10_1101-2021_01_07_425675 119 18 200 200 CD 10_1101-2021_01_07_425675 119 19 mM mM NNP 10_1101-2021_01_07_425675 119 20 Tris Tris NNP 10_1101-2021_01_07_425675 119 21 - - HYPH 10_1101-2021_01_07_425675 119 22 HCl HCl NNP 10_1101-2021_01_07_425675 119 23 , , , 10_1101-2021_01_07_425675 119 24 10 10 CD 10_1101-2021_01_07_425675 119 25 mM mm NN 10_1101-2021_01_07_425675 119 26 tris(2-carboxyethyl)phosphine tris(2-carboxyethyl)phosphine NNP 10_1101-2021_01_07_425675 119 27 ( ( -LRB- 10_1101-2021_01_07_425675 119 28 TCEP TCEP NNP 10_1101-2021_01_07_425675 119 29 ) ) -RRB- 10_1101-2021_01_07_425675 119 30 , , , 10_1101-2021_01_07_425675 119 31 pH pH NNP 10_1101-2021_01_07_425675 119 32 8.0 8.0 CD 10_1101-2021_01_07_425675 119 33 at at IN 10_1101-2021_01_07_425675 119 34 234 234 CD 10_1101-2021_01_07_425675 119 35 95 95 CD 10_1101-2021_01_07_425675 119 36 ° ° , 10_1101-2021_01_07_425675 119 37 C C NNP 10_1101-2021_01_07_425675 119 38 for for IN 10_1101-2021_01_07_425675 119 39 10 10 CD 10_1101-2021_01_07_425675 119 40 min min NN 10_1101-2021_01_07_425675 119 41 , , , 10_1101-2021_01_07_425675 119 42 followed follow VBN 10_1101-2021_01_07_425675 119 43 with with IN 10_1101-2021_01_07_425675 119 44 30 30 CD 10_1101-2021_01_07_425675 119 45 min min NN 10_1101-2021_01_07_425675 119 46 incubation incubation NN 10_1101-2021_01_07_425675 119 47 at at IN 10_1101-2021_01_07_425675 119 48 37 37 CD 10_1101-2021_01_07_425675 119 49 ° ° , 10_1101-2021_01_07_425675 119 50 C C NNP 10_1101-2021_01_07_425675 119 51 for for IN 10_1101-2021_01_07_425675 119 52 reduction reduction NN 10_1101-2021_01_07_425675 119 53 . . . 10_1101-2021_01_07_425675 120 1 Sample Sample NNP 10_1101-2021_01_07_425675 120 2 was be VBD 10_1101-2021_01_07_425675 120 3 then then RB 10_1101-2021_01_07_425675 120 4 alkylated alkylate VBN 10_1101-2021_01_07_425675 120 5 235 235 CD 10_1101-2021_01_07_425675 120 6 by by IN 10_1101-2021_01_07_425675 120 7 adding add VBG 10_1101-2021_01_07_425675 120 8 iodoacetic iodoacetic JJ 10_1101-2021_01_07_425675 120 9 acid acid NN 10_1101-2021_01_07_425675 120 10 to to IN 10_1101-2021_01_07_425675 120 11 a a DT 10_1101-2021_01_07_425675 120 12 final final JJ 10_1101-2021_01_07_425675 120 13 concentration concentration NN 10_1101-2021_01_07_425675 120 14 of of IN 10_1101-2021_01_07_425675 120 15 40 40 CD 10_1101-2021_01_07_425675 120 16 mM mm NN 10_1101-2021_01_07_425675 120 17 and and CC 10_1101-2021_01_07_425675 120 18 incubated incubate VBD 10_1101-2021_01_07_425675 120 19 in in IN 10_1101-2021_01_07_425675 120 20 the the DT 10_1101-2021_01_07_425675 120 21 dark dark NN 10_1101-2021_01_07_425675 120 22 at at IN 10_1101-2021_01_07_425675 120 23 room room NN 10_1101-2021_01_07_425675 120 24 236 236 CD 10_1101-2021_01_07_425675 120 25 temperature temperature NN 10_1101-2021_01_07_425675 120 26 for for IN 10_1101-2021_01_07_425675 120 27 45 45 CD 10_1101-2021_01_07_425675 120 28 min min NN 10_1101-2021_01_07_425675 120 29 . . . 10_1101-2021_01_07_425675 121 1 3 3 LS 10_1101-2021_01_07_425675 121 2 μg μg NNP 10_1101-2021_01_07_425675 121 3 Sample Sample NNP 10_1101-2021_01_07_425675 121 4 was be VBD 10_1101-2021_01_07_425675 121 5 then then RB 10_1101-2021_01_07_425675 121 6 digested digest VBN 10_1101-2021_01_07_425675 121 7 by by IN 10_1101-2021_01_07_425675 121 8 one one CD 10_1101-2021_01_07_425675 121 9 of of IN 10_1101-2021_01_07_425675 121 10 the the DT 10_1101-2021_01_07_425675 121 11 following follow VBG 10_1101-2021_01_07_425675 121 12 proteases protease NNS 10_1101-2021_01_07_425675 121 13 : : : 10_1101-2021_01_07_425675 121 14 trypsin trypsin NNP 10_1101-2021_01_07_425675 121 15 , , , 10_1101-2021_01_07_425675 121 16 237 237 CD 10_1101-2021_01_07_425675 121 17 chymotrypsin chymotrypsin NN 10_1101-2021_01_07_425675 121 18 , , , 10_1101-2021_01_07_425675 121 19 lysN lysn CD 10_1101-2021_01_07_425675 121 20 , , , 10_1101-2021_01_07_425675 121 21 lysC lysC NNP 10_1101-2021_01_07_425675 121 22 , , , 10_1101-2021_01_07_425675 121 23 gluC gluC NNP 10_1101-2021_01_07_425675 121 24 , , , 10_1101-2021_01_07_425675 121 25 aspN aspn CD 10_1101-2021_01_07_425675 121 26 , , , 10_1101-2021_01_07_425675 121 27 aLP alp RB 10_1101-2021_01_07_425675 121 28 , , , 10_1101-2021_01_07_425675 121 29 thermolysin thermolysin NN 10_1101-2021_01_07_425675 121 30 and and CC 10_1101-2021_01_07_425675 121 31 elastase elastase NN 10_1101-2021_01_07_425675 121 32 in in IN 10_1101-2021_01_07_425675 121 33 a a DT 10_1101-2021_01_07_425675 121 34 1:50 1:50 CD 10_1101-2021_01_07_425675 121 35 ratio ratio NN 10_1101-2021_01_07_425675 121 36 ( ( -LRB- 10_1101-2021_01_07_425675 121 37 w w NNP 10_1101-2021_01_07_425675 121 38 : : : 10_1101-2021_01_07_425675 121 39 w w NNP 10_1101-2021_01_07_425675 121 40 ) ) -RRB- 10_1101-2021_01_07_425675 121 41 in in IN 10_1101-2021_01_07_425675 121 42 a a DT 10_1101-2021_01_07_425675 121 43 238 238 CD 10_1101-2021_01_07_425675 121 44 total total JJ 10_1101-2021_01_07_425675 121 45 volume volume NN 10_1101-2021_01_07_425675 121 46 of of IN 10_1101-2021_01_07_425675 121 47 100 100 CD 10_1101-2021_01_07_425675 121 48 uL uL NNP 10_1101-2021_01_07_425675 121 49 of of IN 10_1101-2021_01_07_425675 121 50 50 50 CD 10_1101-2021_01_07_425675 121 51 mM mM NNP 10_1101-2021_01_07_425675 121 52 ammonium ammonium NN 10_1101-2021_01_07_425675 121 53 bicarbonate bicarbonate NN 10_1101-2021_01_07_425675 121 54 at at IN 10_1101-2021_01_07_425675 121 55 37 37 CD 10_1101-2021_01_07_425675 121 56 ° ° , 10_1101-2021_01_07_425675 121 57 C C NNP 10_1101-2021_01_07_425675 121 58 for for IN 10_1101-2021_01_07_425675 121 59 4 4 CD 10_1101-2021_01_07_425675 121 60 h. h. NN 10_1101-2021_01_07_425675 121 61 After after IN 10_1101-2021_01_07_425675 121 62 digestion digestion NN 10_1101-2021_01_07_425675 121 63 , , , 10_1101-2021_01_07_425675 121 64 SDC SDC NNP 10_1101-2021_01_07_425675 121 65 239 239 CD 10_1101-2021_01_07_425675 121 66 was be VBD 10_1101-2021_01_07_425675 121 67 removed remove VBN 10_1101-2021_01_07_425675 121 68 by by IN 10_1101-2021_01_07_425675 121 69 adding add VBG 10_1101-2021_01_07_425675 121 70 2 2 CD 10_1101-2021_01_07_425675 121 71 uL uL NNP 10_1101-2021_01_07_425675 121 72 formic formic NN 10_1101-2021_01_07_425675 121 73 acid acid NN 10_1101-2021_01_07_425675 121 74 ( ( -LRB- 10_1101-2021_01_07_425675 121 75 FA FA NNP 10_1101-2021_01_07_425675 121 76 ) ) -RRB- 10_1101-2021_01_07_425675 121 77 and and CC 10_1101-2021_01_07_425675 121 78 centrifugation centrifugation NN 10_1101-2021_01_07_425675 121 79 at at IN 10_1101-2021_01_07_425675 121 80 14000 14000 CD 10_1101-2021_01_07_425675 121 81 g g NN 10_1101-2021_01_07_425675 121 82 for for IN 10_1101-2021_01_07_425675 121 83 20 20 CD 10_1101-2021_01_07_425675 121 84 min min NN 10_1101-2021_01_07_425675 121 85 . . . 10_1101-2021_01_07_425675 122 1 Following follow VBG 10_1101-2021_01_07_425675 122 2 240 240 CD 10_1101-2021_01_07_425675 122 3 centrifugation centrifugation NN 10_1101-2021_01_07_425675 122 4 , , , 10_1101-2021_01_07_425675 122 5 the the DT 10_1101-2021_01_07_425675 122 6 supernatant supernatant NN 10_1101-2021_01_07_425675 122 7 containing contain VBG 10_1101-2021_01_07_425675 122 8 the the DT 10_1101-2021_01_07_425675 122 9 peptides peptide NNS 10_1101-2021_01_07_425675 122 10 was be VBD 10_1101-2021_01_07_425675 122 11 collected collect VBN 10_1101-2021_01_07_425675 122 12 for for IN 10_1101-2021_01_07_425675 122 13 desalting desalt VBG 10_1101-2021_01_07_425675 122 14 on on IN 10_1101-2021_01_07_425675 122 15 a a DT 10_1101-2021_01_07_425675 122 16 30 30 CD 10_1101-2021_01_07_425675 122 17 µm µm NNP 10_1101-2021_01_07_425675 122 18 241 241 CD 10_1101-2021_01_07_425675 122 19 Oasis oasis NN 10_1101-2021_01_07_425675 122 20 HLB HLB NNP 10_1101-2021_01_07_425675 122 21 96-well 96-well CD 10_1101-2021_01_07_425675 122 22 plate plate NN 10_1101-2021_01_07_425675 122 23 ( ( -LRB- 10_1101-2021_01_07_425675 122 24 Waters Waters NNP 10_1101-2021_01_07_425675 122 25 ) ) -RRB- 10_1101-2021_01_07_425675 122 26 . . . 10_1101-2021_01_07_425675 123 1 The the DT 10_1101-2021_01_07_425675 123 2 Oasis Oasis NNP 10_1101-2021_01_07_425675 123 3 HLB HLB NNP 10_1101-2021_01_07_425675 123 4 sorbent sorbent JJ 10_1101-2021_01_07_425675 123 5 was be VBD 10_1101-2021_01_07_425675 123 6 activated activate VBN 10_1101-2021_01_07_425675 123 7 with with IN 10_1101-2021_01_07_425675 123 8 100 100 CD 10_1101-2021_01_07_425675 123 9 % % NN 10_1101-2021_01_07_425675 123 10 acetonitrile acetonitrile JJ 10_1101-2021_01_07_425675 123 11 242 242 CD 10_1101-2021_01_07_425675 123 12 and and CC 10_1101-2021_01_07_425675 123 13 subsequently subsequently RB 10_1101-2021_01_07_425675 123 14 equilibrated equilibrate VBN 10_1101-2021_01_07_425675 123 15 with with IN 10_1101-2021_01_07_425675 123 16 10 10 CD 10_1101-2021_01_07_425675 123 17 % % NN 10_1101-2021_01_07_425675 123 18 formic formic NN 10_1101-2021_01_07_425675 123 19 acid acid NN 10_1101-2021_01_07_425675 123 20 in in IN 10_1101-2021_01_07_425675 123 21 water water NN 10_1101-2021_01_07_425675 123 22 . . . 10_1101-2021_01_07_425675 124 1 Next next RB 10_1101-2021_01_07_425675 124 2 , , , 10_1101-2021_01_07_425675 124 3 peptides peptide NNS 10_1101-2021_01_07_425675 124 4 were be VBD 10_1101-2021_01_07_425675 124 5 bound bind VBN 10_1101-2021_01_07_425675 124 6 to to IN 10_1101-2021_01_07_425675 124 7 the the DT 10_1101-2021_01_07_425675 124 8 243 243 CD 10_1101-2021_01_07_425675 124 9 sorbent sorbent JJ 10_1101-2021_01_07_425675 124 10 , , , 10_1101-2021_01_07_425675 124 11 washed wash VBD 10_1101-2021_01_07_425675 124 12 twice twice RB 10_1101-2021_01_07_425675 124 13 with with IN 10_1101-2021_01_07_425675 124 14 10 10 CD 10_1101-2021_01_07_425675 124 15 % % NN 10_1101-2021_01_07_425675 124 16 formic formic NN 10_1101-2021_01_07_425675 124 17 acid acid NN 10_1101-2021_01_07_425675 124 18 in in IN 10_1101-2021_01_07_425675 124 19 water water NN 10_1101-2021_01_07_425675 124 20 and and CC 10_1101-2021_01_07_425675 124 21 eluted elute VBD 10_1101-2021_01_07_425675 124 22 with with IN 10_1101-2021_01_07_425675 124 23 100 100 CD 10_1101-2021_01_07_425675 124 24 µL µl CD 10_1101-2021_01_07_425675 124 25 of of IN 10_1101-2021_01_07_425675 124 26 50 50 CD 10_1101-2021_01_07_425675 124 27 % % NN 10_1101-2021_01_07_425675 124 28 244 244 CD 10_1101-2021_01_07_425675 124 29 acetonitrile/5 acetonitrile/5 CD 10_1101-2021_01_07_425675 124 30 % % NN 10_1101-2021_01_07_425675 124 31 formic formic NN 10_1101-2021_01_07_425675 124 32 acid acid NN 10_1101-2021_01_07_425675 124 33 in in IN 10_1101-2021_01_07_425675 124 34 water water NN 10_1101-2021_01_07_425675 124 35 ( ( -LRB- 10_1101-2021_01_07_425675 124 36 v v NN 10_1101-2021_01_07_425675 124 37 / / SYM 10_1101-2021_01_07_425675 124 38 v v NNP 10_1101-2021_01_07_425675 124 39 ) ) -RRB- 10_1101-2021_01_07_425675 124 40 . . . 10_1101-2021_01_07_425675 125 1 The the DT 10_1101-2021_01_07_425675 125 2 eluted elute VBN 10_1101-2021_01_07_425675 125 3 peptides peptide NNS 10_1101-2021_01_07_425675 125 4 were be VBD 10_1101-2021_01_07_425675 125 5 vacuum vacuum NN 10_1101-2021_01_07_425675 125 6 - - HYPH 10_1101-2021_01_07_425675 125 7 dried dry VBN 10_1101-2021_01_07_425675 125 8 and and CC 10_1101-2021_01_07_425675 125 9 245 245 CD 10_1101-2021_01_07_425675 125 10 reconstituted reconstitute VBD 10_1101-2021_01_07_425675 125 11 in in IN 10_1101-2021_01_07_425675 125 12 100 100 CD 10_1101-2021_01_07_425675 125 13 µL µl $ 10_1101-2021_01_07_425675 125 14 2 2 CD 10_1101-2021_01_07_425675 125 15 % % NN 10_1101-2021_01_07_425675 125 16 FA fa NN 10_1101-2021_01_07_425675 125 17 . . . 10_1101-2021_01_07_425675 126 1 246 246 CD 10_1101-2021_01_07_425675 126 2 247 247 CD 10_1101-2021_01_07_425675 126 3 .CC .CC : 10_1101-2021_01_07_425675 126 4 - - : 10_1101-2021_01_07_425675 126 5 BY by IN 10_1101-2021_01_07_425675 126 6 4.0 4.0 CD 10_1101-2021_01_07_425675 126 7 International International NNP 10_1101-2021_01_07_425675 126 8 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 126 9 under under IN 10_1101-2021_01_07_425675 126 10 a a DT 10_1101-2021_01_07_425675 126 11 ( ( -LRB- 10_1101-2021_01_07_425675 126 12 which which WDT 10_1101-2021_01_07_425675 126 13 was be VBD 10_1101-2021_01_07_425675 126 14 not not RB 10_1101-2021_01_07_425675 126 15 certified certify VBN 10_1101-2021_01_07_425675 126 16 by by IN 10_1101-2021_01_07_425675 126 17 peer peer NN 10_1101-2021_01_07_425675 126 18 review review NN 10_1101-2021_01_07_425675 126 19 ) ) -RRB- 10_1101-2021_01_07_425675 126 20 is be VBZ 10_1101-2021_01_07_425675 126 21 the the DT 10_1101-2021_01_07_425675 126 22 author author NN 10_1101-2021_01_07_425675 126 23 / / SYM 10_1101-2021_01_07_425675 126 24 funder funder NN 10_1101-2021_01_07_425675 126 25 , , , 10_1101-2021_01_07_425675 126 26 who who WP 10_1101-2021_01_07_425675 126 27 has have VBZ 10_1101-2021_01_07_425675 126 28 granted grant VBN 10_1101-2021_01_07_425675 126 29 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 126 30 a a DT 10_1101-2021_01_07_425675 126 31 license license NN 10_1101-2021_01_07_425675 126 32 to to TO 10_1101-2021_01_07_425675 126 33 display display VB 10_1101-2021_01_07_425675 126 34 the the DT 10_1101-2021_01_07_425675 126 35 preprint preprint NN 10_1101-2021_01_07_425675 126 36 in in IN 10_1101-2021_01_07_425675 126 37 perpetuity perpetuity NN 10_1101-2021_01_07_425675 126 38 . . . 10_1101-2021_01_07_425675 127 1 It -PRON- PRP 10_1101-2021_01_07_425675 127 2 is be VBZ 10_1101-2021_01_07_425675 127 3 made make VBN 10_1101-2021_01_07_425675 127 4 The the DT 10_1101-2021_01_07_425675 127 5 copyright copyright NN 10_1101-2021_01_07_425675 127 6 holder holder NN 10_1101-2021_01_07_425675 127 7 for for IN 10_1101-2021_01_07_425675 127 8 this this DT 10_1101-2021_01_07_425675 127 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 127 10 version version NN 10_1101-2021_01_07_425675 127 11 posted post VBD 10_1101-2021_01_07_425675 127 12 January January NNP 10_1101-2021_01_07_425675 127 13 8 8 CD 10_1101-2021_01_07_425675 127 14 , , , 10_1101-2021_01_07_425675 127 15 2021 2021 CD 10_1101-2021_01_07_425675 127 16 . . . 10_1101-2021_01_07_425675 127 17 ; ; : 10_1101-2021_01_07_425675 127 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 127 19 : : : 10_1101-2021_01_07_425675 127 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 127 21 preprint preprint NN 10_1101-2021_01_07_425675 127 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 127 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 127 24 11 11 CD 10_1101-2021_01_07_425675 127 25 Mass Mass NNP 10_1101-2021_01_07_425675 127 26 Spectrometry Spectrometry NNP 10_1101-2021_01_07_425675 127 27 248 248 CD 10_1101-2021_01_07_425675 127 28 The the DT 10_1101-2021_01_07_425675 127 29 digested digest VBN 10_1101-2021_01_07_425675 127 30 peptides peptide NNS 10_1101-2021_01_07_425675 127 31 ( ( -LRB- 10_1101-2021_01_07_425675 127 32 single single JJ 10_1101-2021_01_07_425675 127 33 injection injection NN 10_1101-2021_01_07_425675 127 34 of of IN 10_1101-2021_01_07_425675 127 35 0.2 0.2 CD 10_1101-2021_01_07_425675 127 36 ug ug NNS 10_1101-2021_01_07_425675 127 37 ) ) -RRB- 10_1101-2021_01_07_425675 127 38 were be VBD 10_1101-2021_01_07_425675 127 39 separated separate VBN 10_1101-2021_01_07_425675 127 40 by by IN 10_1101-2021_01_07_425675 127 41 online online JJ 10_1101-2021_01_07_425675 127 42 reversed reversed JJ 10_1101-2021_01_07_425675 127 43 phase phase NN 10_1101-2021_01_07_425675 127 44 249 249 CD 10_1101-2021_01_07_425675 127 45 chromatography chromatography NN 10_1101-2021_01_07_425675 127 46 on on IN 10_1101-2021_01_07_425675 127 47 an an DT 10_1101-2021_01_07_425675 127 48 Agilent Agilent NNP 10_1101-2021_01_07_425675 127 49 1290 1290 CD 10_1101-2021_01_07_425675 127 50 UHPLC UHPLC NNP 10_1101-2021_01_07_425675 127 51 ( ( -LRB- 10_1101-2021_01_07_425675 127 52 column column NN 10_1101-2021_01_07_425675 127 53 packed pack VBN 10_1101-2021_01_07_425675 127 54 with with IN 10_1101-2021_01_07_425675 127 55 Poroshell Poroshell NNP 10_1101-2021_01_07_425675 127 56 120 120 CD 10_1101-2021_01_07_425675 127 57 EC EC NNP 10_1101-2021_01_07_425675 127 58 C18 C18 NNP 10_1101-2021_01_07_425675 127 59 ; ; : 10_1101-2021_01_07_425675 127 60 250 250 CD 10_1101-2021_01_07_425675 127 61 dimensions dimension NNS 10_1101-2021_01_07_425675 127 62 50 50 CD 10_1101-2021_01_07_425675 127 63 cm cm NNS 10_1101-2021_01_07_425675 127 64 x x NNP 10_1101-2021_01_07_425675 127 65 75 75 CD 10_1101-2021_01_07_425675 127 66 µm µm NNP 10_1101-2021_01_07_425675 127 67 , , , 10_1101-2021_01_07_425675 127 68 2.7 2.7 CD 10_1101-2021_01_07_425675 127 69 µm µm NNP 10_1101-2021_01_07_425675 127 70 , , , 10_1101-2021_01_07_425675 127 71 Agilent Agilent NNP 10_1101-2021_01_07_425675 127 72 Technologies Technologies NNP 10_1101-2021_01_07_425675 127 73 ) ) -RRB- 10_1101-2021_01_07_425675 127 74 coupled couple VBD 10_1101-2021_01_07_425675 127 75 to to IN 10_1101-2021_01_07_425675 127 76 a a DT 10_1101-2021_01_07_425675 127 77 Thermo Thermo NNP 10_1101-2021_01_07_425675 127 78 Scientific Scientific NNP 10_1101-2021_01_07_425675 127 79 Orbitrap Orbitrap NNP 10_1101-2021_01_07_425675 127 80 251 251 NNP 10_1101-2021_01_07_425675 127 81 Fusion Fusion NNP 10_1101-2021_01_07_425675 127 82 mass mass NN 10_1101-2021_01_07_425675 127 83 spectrometer spectrometer NN 10_1101-2021_01_07_425675 127 84 . . . 10_1101-2021_01_07_425675 128 1 Samples sample NNS 10_1101-2021_01_07_425675 128 2 were be VBD 10_1101-2021_01_07_425675 128 3 eluted elute VBN 10_1101-2021_01_07_425675 128 4 over over IN 10_1101-2021_01_07_425675 128 5 a a DT 10_1101-2021_01_07_425675 128 6 90 90 CD 10_1101-2021_01_07_425675 128 7 min min NN 10_1101-2021_01_07_425675 128 8 gradient gradient NN 10_1101-2021_01_07_425675 128 9 from from IN 10_1101-2021_01_07_425675 128 10 0 0 CD 10_1101-2021_01_07_425675 128 11 % % NN 10_1101-2021_01_07_425675 128 12 to to TO 10_1101-2021_01_07_425675 128 13 35 35 CD 10_1101-2021_01_07_425675 128 14 % % NN 10_1101-2021_01_07_425675 128 15 252 252 CD 10_1101-2021_01_07_425675 128 16 acetonitrile acetonitrile NN 10_1101-2021_01_07_425675 128 17 at at IN 10_1101-2021_01_07_425675 128 18 a a DT 10_1101-2021_01_07_425675 128 19 flow flow NN 10_1101-2021_01_07_425675 128 20 rate rate NN 10_1101-2021_01_07_425675 128 21 of of IN 10_1101-2021_01_07_425675 128 22 0.3 0.3 CD 10_1101-2021_01_07_425675 128 23 μL μL NNP 10_1101-2021_01_07_425675 128 24 / / SYM 10_1101-2021_01_07_425675 128 25 min min NNP 10_1101-2021_01_07_425675 128 26 . . . 10_1101-2021_01_07_425675 129 1 Peptides peptide NNS 10_1101-2021_01_07_425675 129 2 were be VBD 10_1101-2021_01_07_425675 129 3 analyzed analyze VBN 10_1101-2021_01_07_425675 129 4 with with IN 10_1101-2021_01_07_425675 129 5 a a DT 10_1101-2021_01_07_425675 129 6 resolution resolution NN 10_1101-2021_01_07_425675 129 7 setting setting NN 10_1101-2021_01_07_425675 129 8 of of IN 10_1101-2021_01_07_425675 129 9 60000 60000 CD 10_1101-2021_01_07_425675 129 10 253 253 CD 10_1101-2021_01_07_425675 129 11 in in IN 10_1101-2021_01_07_425675 129 12 MS1 MS1 NNP 10_1101-2021_01_07_425675 129 13 . . . 10_1101-2021_01_07_425675 130 1 MS1 MS1 NNP 10_1101-2021_01_07_425675 130 2 scans scan NNS 10_1101-2021_01_07_425675 130 3 were be VBD 10_1101-2021_01_07_425675 130 4 obtained obtain VBN 10_1101-2021_01_07_425675 130 5 with with IN 10_1101-2021_01_07_425675 130 6 standard standard JJ 10_1101-2021_01_07_425675 130 7 AGC AGC NNP 10_1101-2021_01_07_425675 130 8 target target NN 10_1101-2021_01_07_425675 130 9 , , , 10_1101-2021_01_07_425675 130 10 maximum maximum JJ 10_1101-2021_01_07_425675 130 11 injection injection NN 10_1101-2021_01_07_425675 130 12 time time NN 10_1101-2021_01_07_425675 130 13 of of IN 10_1101-2021_01_07_425675 130 14 50 50 CD 10_1101-2021_01_07_425675 130 15 ms m NNS 10_1101-2021_01_07_425675 130 16 , , , 10_1101-2021_01_07_425675 130 17 254 254 CD 10_1101-2021_01_07_425675 130 18 and and CC 10_1101-2021_01_07_425675 130 19 scan scan NNP 10_1101-2021_01_07_425675 130 20 range range NNP 10_1101-2021_01_07_425675 130 21 350 350 CD 10_1101-2021_01_07_425675 130 22 - - HYPH 10_1101-2021_01_07_425675 130 23 2000 2000 CD 10_1101-2021_01_07_425675 130 24 . . . 10_1101-2021_01_07_425675 131 1 The the DT 10_1101-2021_01_07_425675 131 2 precursors precursor NNS 10_1101-2021_01_07_425675 131 3 were be VBD 10_1101-2021_01_07_425675 131 4 selected select VBN 10_1101-2021_01_07_425675 131 5 with with IN 10_1101-2021_01_07_425675 131 6 a a DT 10_1101-2021_01_07_425675 131 7 3 3 CD 10_1101-2021_01_07_425675 131 8 m m NN 10_1101-2021_01_07_425675 131 9 / / SYM 10_1101-2021_01_07_425675 131 10 z z NN 10_1101-2021_01_07_425675 131 11 window window NN 10_1101-2021_01_07_425675 131 12 and and CC 10_1101-2021_01_07_425675 131 13 fragmented fragment VBN 10_1101-2021_01_07_425675 131 14 by by IN 10_1101-2021_01_07_425675 131 15 255 255 CD 10_1101-2021_01_07_425675 131 16 stepped step VBD 10_1101-2021_01_07_425675 131 17 HCD HCD NNP 10_1101-2021_01_07_425675 131 18 as as RB 10_1101-2021_01_07_425675 131 19 well well RB 10_1101-2021_01_07_425675 131 20 as as IN 10_1101-2021_01_07_425675 131 21 EThcD. ethcd. RB 10_1101-2021_01_07_425675 132 1 The the DT 10_1101-2021_01_07_425675 132 2 stepped stepped JJ 10_1101-2021_01_07_425675 132 3 HCD HCD NNP 10_1101-2021_01_07_425675 132 4 fragmentation fragmentation NN 10_1101-2021_01_07_425675 132 5 included include VBD 10_1101-2021_01_07_425675 132 6 steps step NNS 10_1101-2021_01_07_425675 132 7 of of IN 10_1101-2021_01_07_425675 132 8 25 25 CD 10_1101-2021_01_07_425675 132 9 % % NN 10_1101-2021_01_07_425675 132 10 , , , 10_1101-2021_01_07_425675 132 11 35 35 CD 10_1101-2021_01_07_425675 132 12 % % NN 10_1101-2021_01_07_425675 132 13 256 256 CD 10_1101-2021_01_07_425675 132 14 and and CC 10_1101-2021_01_07_425675 132 15 50 50 CD 10_1101-2021_01_07_425675 132 16 % % NN 10_1101-2021_01_07_425675 132 17 NCE NCE NNP 10_1101-2021_01_07_425675 132 18 . . . 10_1101-2021_01_07_425675 133 1 EThcD EThcD NNP 10_1101-2021_01_07_425675 133 2 fragmentation fragmentation NN 10_1101-2021_01_07_425675 133 3 was be VBD 10_1101-2021_01_07_425675 133 4 performed perform VBN 10_1101-2021_01_07_425675 133 5 with with IN 10_1101-2021_01_07_425675 133 6 calibrated calibrate VBN 10_1101-2021_01_07_425675 133 7 charge charge NN 10_1101-2021_01_07_425675 133 8 - - HYPH 10_1101-2021_01_07_425675 133 9 dependent dependent JJ 10_1101-2021_01_07_425675 133 10 ETD ETD NNP 10_1101-2021_01_07_425675 133 11 257 257 CD 10_1101-2021_01_07_425675 133 12 parameters parameter NNS 10_1101-2021_01_07_425675 133 13 and and CC 10_1101-2021_01_07_425675 133 14 27 27 CD 10_1101-2021_01_07_425675 133 15 % % NN 10_1101-2021_01_07_425675 133 16 NCE NCE NNP 10_1101-2021_01_07_425675 133 17 supplemental supplemental JJ 10_1101-2021_01_07_425675 133 18 activation activation NN 10_1101-2021_01_07_425675 133 19 . . . 10_1101-2021_01_07_425675 134 1 For for IN 10_1101-2021_01_07_425675 134 2 both both DT 10_1101-2021_01_07_425675 134 3 fragmentation fragmentation NN 10_1101-2021_01_07_425675 134 4 types type NNS 10_1101-2021_01_07_425675 134 5 , , , 10_1101-2021_01_07_425675 134 6 ms2 ms2 NNP 10_1101-2021_01_07_425675 134 7 scan scan NNP 10_1101-2021_01_07_425675 134 8 were be VBD 10_1101-2021_01_07_425675 134 9 258 258 CD 10_1101-2021_01_07_425675 134 10 acquired acquire VBN 10_1101-2021_01_07_425675 134 11 at at IN 10_1101-2021_01_07_425675 134 12 30000 30000 CD 10_1101-2021_01_07_425675 134 13 resolution resolution NN 10_1101-2021_01_07_425675 134 14 , , , 10_1101-2021_01_07_425675 134 15 800 800 CD 10_1101-2021_01_07_425675 134 16 % % NN 10_1101-2021_01_07_425675 134 17 Normalized Normalized NNP 10_1101-2021_01_07_425675 134 18 AGC AGC NNP 10_1101-2021_01_07_425675 134 19 target target NN 10_1101-2021_01_07_425675 134 20 , , , 10_1101-2021_01_07_425675 134 21 250 250 CD 10_1101-2021_01_07_425675 134 22 ms ms NN 10_1101-2021_01_07_425675 134 23 maximum maximum JJ 10_1101-2021_01_07_425675 134 24 injection injection NN 10_1101-2021_01_07_425675 134 25 time time NN 10_1101-2021_01_07_425675 134 26 , , , 10_1101-2021_01_07_425675 134 27 259 259 CD 10_1101-2021_01_07_425675 134 28 scan scan JJ 10_1101-2021_01_07_425675 134 29 range range NN 10_1101-2021_01_07_425675 134 30 120 120 CD 10_1101-2021_01_07_425675 134 31 - - SYM 10_1101-2021_01_07_425675 134 32 3500 3500 CD 10_1101-2021_01_07_425675 134 33 . . . 10_1101-2021_01_07_425675 135 1 260 260 CD 10_1101-2021_01_07_425675 135 2 261 261 CD 10_1101-2021_01_07_425675 135 3 MS MS NNP 10_1101-2021_01_07_425675 135 4 Data Data NNP 10_1101-2021_01_07_425675 135 5 Analysis Analysis NNP 10_1101-2021_01_07_425675 135 6 262 262 CD 10_1101-2021_01_07_425675 135 7 Automated Automated NNP 10_1101-2021_01_07_425675 135 8 de de NNP 10_1101-2021_01_07_425675 135 9 novo novo NNP 10_1101-2021_01_07_425675 135 10 sequencing sequencing NN 10_1101-2021_01_07_425675 135 11 was be VBD 10_1101-2021_01_07_425675 135 12 performed perform VBN 10_1101-2021_01_07_425675 135 13 with with IN 10_1101-2021_01_07_425675 135 14 Supernovo Supernovo NNP 10_1101-2021_01_07_425675 135 15 ( ( -LRB- 10_1101-2021_01_07_425675 135 16 version version NN 10_1101-2021_01_07_425675 135 17 3.10 3.10 CD 10_1101-2021_01_07_425675 135 18 , , , 10_1101-2021_01_07_425675 135 19 Protein Protein NNP 10_1101-2021_01_07_425675 135 20 Metrics Metrics NNP 10_1101-2021_01_07_425675 135 21 263 263 CD 10_1101-2021_01_07_425675 135 22 Inc. Inc. NNP 10_1101-2021_01_07_425675 135 23 ) ) -RRB- 10_1101-2021_01_07_425675 135 24 . . . 10_1101-2021_01_07_425675 136 1 Custom custom NN 10_1101-2021_01_07_425675 136 2 parameters parameter NNS 10_1101-2021_01_07_425675 136 3 were be VBD 10_1101-2021_01_07_425675 136 4 used use VBN 10_1101-2021_01_07_425675 136 5 as as IN 10_1101-2021_01_07_425675 136 6 follows follow VBZ 10_1101-2021_01_07_425675 136 7 : : : 10_1101-2021_01_07_425675 136 8 non non JJ 10_1101-2021_01_07_425675 136 9 - - JJ 10_1101-2021_01_07_425675 136 10 specific specific JJ 10_1101-2021_01_07_425675 136 11 digestion digestion NN 10_1101-2021_01_07_425675 136 12 ; ; : 10_1101-2021_01_07_425675 136 13 precursor precursor NN 10_1101-2021_01_07_425675 136 14 and and CC 10_1101-2021_01_07_425675 136 15 product product NN 10_1101-2021_01_07_425675 136 16 264 264 CD 10_1101-2021_01_07_425675 136 17 mass mass NN 10_1101-2021_01_07_425675 136 18 tolerance tolerance NN 10_1101-2021_01_07_425675 136 19 was be VBD 10_1101-2021_01_07_425675 136 20 set set VBN 10_1101-2021_01_07_425675 136 21 to to IN 10_1101-2021_01_07_425675 136 22 12 12 CD 10_1101-2021_01_07_425675 136 23 ppm ppm NN 10_1101-2021_01_07_425675 136 24 and and CC 10_1101-2021_01_07_425675 136 25 0.02 0.02 CD 10_1101-2021_01_07_425675 136 26 Da Da NNP 10_1101-2021_01_07_425675 136 27 respectively respectively RB 10_1101-2021_01_07_425675 136 28 ; ; : 10_1101-2021_01_07_425675 136 29 carboxymethylation carboxymethylation NN 10_1101-2021_01_07_425675 136 30 ( ( -LRB- 10_1101-2021_01_07_425675 136 31 +58.005479 +58.005479 NNP 10_1101-2021_01_07_425675 136 32 ) ) -RRB- 10_1101-2021_01_07_425675 136 33 265 265 CD 10_1101-2021_01_07_425675 136 34 on on IN 10_1101-2021_01_07_425675 136 35 cysteine cysteine NN 10_1101-2021_01_07_425675 136 36 was be VBD 10_1101-2021_01_07_425675 136 37 set set VBN 10_1101-2021_01_07_425675 136 38 as as IN 10_1101-2021_01_07_425675 136 39 fixed fix VBN 10_1101-2021_01_07_425675 136 40 modification modification NN 10_1101-2021_01_07_425675 136 41 ; ; : 10_1101-2021_01_07_425675 136 42 oxidation oxidation NN 10_1101-2021_01_07_425675 136 43 on on IN 10_1101-2021_01_07_425675 136 44 methionine methionine NNP 10_1101-2021_01_07_425675 136 45 and and CC 10_1101-2021_01_07_425675 136 46 tryptophan tryptophan NNP 10_1101-2021_01_07_425675 136 47 was be VBD 10_1101-2021_01_07_425675 136 48 set set VBN 10_1101-2021_01_07_425675 136 49 as as IN 10_1101-2021_01_07_425675 136 50 266 266 CD 10_1101-2021_01_07_425675 136 51 variable variable JJ 10_1101-2021_01_07_425675 136 52 common common JJ 10_1101-2021_01_07_425675 136 53 1 1 CD 10_1101-2021_01_07_425675 136 54 modification modification NN 10_1101-2021_01_07_425675 136 55 ; ; : 10_1101-2021_01_07_425675 136 56 carboxymethylation carboxymethylation NN 10_1101-2021_01_07_425675 136 57 on on IN 10_1101-2021_01_07_425675 136 58 the the DT 10_1101-2021_01_07_425675 136 59 N n NN 10_1101-2021_01_07_425675 136 60 - - HYPH 10_1101-2021_01_07_425675 136 61 terminus terminus NN 10_1101-2021_01_07_425675 136 62 , , , 10_1101-2021_01_07_425675 136 63 pyroglutamic pyroglutamic JJ 10_1101-2021_01_07_425675 136 64 acid acid NN 10_1101-2021_01_07_425675 136 65 267 267 CD 10_1101-2021_01_07_425675 136 66 conversion conversion NN 10_1101-2021_01_07_425675 136 67 of of IN 10_1101-2021_01_07_425675 136 68 glutamine glutamine NN 10_1101-2021_01_07_425675 136 69 and and CC 10_1101-2021_01_07_425675 136 70 glutamic glutamic NN 10_1101-2021_01_07_425675 136 71 acid acid NN 10_1101-2021_01_07_425675 136 72 on on IN 10_1101-2021_01_07_425675 136 73 the the DT 10_1101-2021_01_07_425675 136 74 N n NN 10_1101-2021_01_07_425675 136 75 - - HYPH 10_1101-2021_01_07_425675 136 76 terminus terminus NN 10_1101-2021_01_07_425675 136 77 , , , 10_1101-2021_01_07_425675 136 78 deamidation deamidation NN 10_1101-2021_01_07_425675 136 79 on on IN 10_1101-2021_01_07_425675 136 80 268 268 CD 10_1101-2021_01_07_425675 136 81 asparagine asparagine NN 10_1101-2021_01_07_425675 136 82 / / SYM 10_1101-2021_01_07_425675 136 83 glutamine glutamine NN 10_1101-2021_01_07_425675 136 84 were be VBD 10_1101-2021_01_07_425675 136 85 set set VBN 10_1101-2021_01_07_425675 136 86 as as IN 10_1101-2021_01_07_425675 136 87 variable variable JJ 10_1101-2021_01_07_425675 136 88 rare rare JJ 10_1101-2021_01_07_425675 136 89 1 1 CD 10_1101-2021_01_07_425675 136 90 modifications modification NNS 10_1101-2021_01_07_425675 136 91 . . . 10_1101-2021_01_07_425675 137 1 Peptides peptide NNS 10_1101-2021_01_07_425675 137 2 were be VBD 10_1101-2021_01_07_425675 137 3 filtered filter VBN 10_1101-2021_01_07_425675 137 4 for for IN 10_1101-2021_01_07_425675 137 5 score score NN 10_1101-2021_01_07_425675 137 6 269 269 CD 10_1101-2021_01_07_425675 137 7 > > NNS 10_1101-2021_01_07_425675 137 8 = = SYM 10_1101-2021_01_07_425675 137 9 500 500 CD 10_1101-2021_01_07_425675 137 10 for for IN 10_1101-2021_01_07_425675 137 11 the the DT 10_1101-2021_01_07_425675 137 12 final final JJ 10_1101-2021_01_07_425675 137 13 evaluation evaluation NN 10_1101-2021_01_07_425675 137 14 of of IN 10_1101-2021_01_07_425675 137 15 spectrum spectrum NN 10_1101-2021_01_07_425675 137 16 quality quality NN 10_1101-2021_01_07_425675 137 17 and and CC 10_1101-2021_01_07_425675 137 18 ( ( -LRB- 10_1101-2021_01_07_425675 137 19 depth depth NN 10_1101-2021_01_07_425675 137 20 of of IN 10_1101-2021_01_07_425675 137 21 ) ) -RRB- 10_1101-2021_01_07_425675 137 22 coverage coverage NN 10_1101-2021_01_07_425675 137 23 . . . 10_1101-2021_01_07_425675 138 1 Supernovo Supernovo NNP 10_1101-2021_01_07_425675 138 2 generates generate VBZ 10_1101-2021_01_07_425675 138 3 270 270 CD 10_1101-2021_01_07_425675 138 4 peptide peptide JJ 10_1101-2021_01_07_425675 138 5 groups group NNS 10_1101-2021_01_07_425675 138 6 for for IN 10_1101-2021_01_07_425675 138 7 redundant redundant JJ 10_1101-2021_01_07_425675 138 8 MS MS NNP 10_1101-2021_01_07_425675 138 9 / / SYM 10_1101-2021_01_07_425675 138 10 MS MS NNP 10_1101-2021_01_07_425675 138 11 spectra spectra NNP 10_1101-2021_01_07_425675 138 12 , , , 10_1101-2021_01_07_425675 138 13 including include VBG 10_1101-2021_01_07_425675 138 14 also also RB 10_1101-2021_01_07_425675 138 15 when when WRB 10_1101-2021_01_07_425675 138 16 stepped step VBN 10_1101-2021_01_07_425675 138 17 HCD HCD NNP 10_1101-2021_01_07_425675 138 18 and and CC 10_1101-2021_01_07_425675 138 19 EThcD EThcD NNP 10_1101-2021_01_07_425675 138 20 271 271 CD 10_1101-2021_01_07_425675 138 21 fragmentation fragmentation NN 10_1101-2021_01_07_425675 138 22 on on IN 10_1101-2021_01_07_425675 138 23 the the DT 10_1101-2021_01_07_425675 138 24 same same JJ 10_1101-2021_01_07_425675 138 25 precursor precursor NN 10_1101-2021_01_07_425675 138 26 both both CC 10_1101-2021_01_07_425675 138 27 generate generate VBP 10_1101-2021_01_07_425675 138 28 good good JJ 10_1101-2021_01_07_425675 138 29 peptide peptide NN 10_1101-2021_01_07_425675 138 30 - - HYPH 10_1101-2021_01_07_425675 138 31 spectrum spectrum NN 10_1101-2021_01_07_425675 138 32 matches match NNS 10_1101-2021_01_07_425675 138 33 . . . 10_1101-2021_01_07_425675 139 1 In in IN 10_1101-2021_01_07_425675 139 2 these these DT 10_1101-2021_01_07_425675 139 3 272 272 CD 10_1101-2021_01_07_425675 139 4 cases case NNS 10_1101-2021_01_07_425675 139 5 only only RB 10_1101-2021_01_07_425675 139 6 the the DT 10_1101-2021_01_07_425675 139 7 best well RBS 10_1101-2021_01_07_425675 139 8 - - HYPH 10_1101-2021_01_07_425675 139 9 matched match VBN 10_1101-2021_01_07_425675 139 10 spectrum spectrum NN 10_1101-2021_01_07_425675 139 11 is be VBZ 10_1101-2021_01_07_425675 139 12 counted count VBN 10_1101-2021_01_07_425675 139 13 as as IN 10_1101-2021_01_07_425675 139 14 representative representative NN 10_1101-2021_01_07_425675 139 15 for for IN 10_1101-2021_01_07_425675 139 16 that that DT 10_1101-2021_01_07_425675 139 17 group group NN 10_1101-2021_01_07_425675 139 18 . . . 10_1101-2021_01_07_425675 140 1 This this DT 10_1101-2021_01_07_425675 140 2 criterium criterium NN 10_1101-2021_01_07_425675 140 3 273 273 CD 10_1101-2021_01_07_425675 140 4 was be VBD 10_1101-2021_01_07_425675 140 5 used use VBN 10_1101-2021_01_07_425675 140 6 in in IN 10_1101-2021_01_07_425675 140 7 counting count VBG 10_1101-2021_01_07_425675 140 8 the the DT 10_1101-2021_01_07_425675 140 9 number number NN 10_1101-2021_01_07_425675 140 10 of of IN 10_1101-2021_01_07_425675 140 11 peptide peptide NN 10_1101-2021_01_07_425675 140 12 reads read NNS 10_1101-2021_01_07_425675 140 13 reported report VBN 10_1101-2021_01_07_425675 140 14 in in IN 10_1101-2021_01_07_425675 140 15 Table table NN 10_1101-2021_01_07_425675 140 16 S1 S1 NNS 10_1101-2021_01_07_425675 140 17 . . . 10_1101-2021_01_07_425675 141 1 Germline germline JJ 10_1101-2021_01_07_425675 141 2 sequences sequence NNS 10_1101-2021_01_07_425675 141 3 and and CC 10_1101-2021_01_07_425675 141 4 274 274 CD 10_1101-2021_01_07_425675 141 5 CDR cdr NN 10_1101-2021_01_07_425675 141 6 boundaries boundary NNS 10_1101-2021_01_07_425675 141 7 were be VBD 10_1101-2021_01_07_425675 141 8 inferred infer VBN 10_1101-2021_01_07_425675 141 9 using use VBG 10_1101-2021_01_07_425675 141 10 IMGT IMGT NNP 10_1101-2021_01_07_425675 141 11 / / SYM 10_1101-2021_01_07_425675 141 12 DomainGapAlign DomainGapAlign NNP 10_1101-2021_01_07_425675 141 13 38 38 CD 10_1101-2021_01_07_425675 141 14 - - SYM 10_1101-2021_01_07_425675 141 15 39 39 CD 10_1101-2021_01_07_425675 141 16 . . . 10_1101-2021_01_07_425675 142 1 275 275 CD 10_1101-2021_01_07_425675 142 2 276 276 CD 10_1101-2021_01_07_425675 142 3 277 277 CD 10_1101-2021_01_07_425675 142 4 278 278 CD 10_1101-2021_01_07_425675 142 5 .CC .CC , 10_1101-2021_01_07_425675 142 6 - - : 10_1101-2021_01_07_425675 142 7 BY by IN 10_1101-2021_01_07_425675 142 8 4.0 4.0 CD 10_1101-2021_01_07_425675 142 9 International International NNP 10_1101-2021_01_07_425675 142 10 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 142 11 under under IN 10_1101-2021_01_07_425675 142 12 a a DT 10_1101-2021_01_07_425675 142 13 ( ( -LRB- 10_1101-2021_01_07_425675 142 14 which which WDT 10_1101-2021_01_07_425675 142 15 was be VBD 10_1101-2021_01_07_425675 142 16 not not RB 10_1101-2021_01_07_425675 142 17 certified certify VBN 10_1101-2021_01_07_425675 142 18 by by IN 10_1101-2021_01_07_425675 142 19 peer peer NN 10_1101-2021_01_07_425675 142 20 review review NN 10_1101-2021_01_07_425675 142 21 ) ) -RRB- 10_1101-2021_01_07_425675 142 22 is be VBZ 10_1101-2021_01_07_425675 142 23 the the DT 10_1101-2021_01_07_425675 142 24 author author NN 10_1101-2021_01_07_425675 142 25 / / SYM 10_1101-2021_01_07_425675 142 26 funder funder NN 10_1101-2021_01_07_425675 142 27 , , , 10_1101-2021_01_07_425675 142 28 who who WP 10_1101-2021_01_07_425675 142 29 has have VBZ 10_1101-2021_01_07_425675 142 30 granted grant VBN 10_1101-2021_01_07_425675 142 31 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 142 32 a a DT 10_1101-2021_01_07_425675 142 33 license license NN 10_1101-2021_01_07_425675 142 34 to to TO 10_1101-2021_01_07_425675 142 35 display display VB 10_1101-2021_01_07_425675 142 36 the the DT 10_1101-2021_01_07_425675 142 37 preprint preprint NN 10_1101-2021_01_07_425675 142 38 in in IN 10_1101-2021_01_07_425675 142 39 perpetuity perpetuity NN 10_1101-2021_01_07_425675 142 40 . . . 10_1101-2021_01_07_425675 143 1 It -PRON- PRP 10_1101-2021_01_07_425675 143 2 is be VBZ 10_1101-2021_01_07_425675 143 3 made make VBN 10_1101-2021_01_07_425675 143 4 The the DT 10_1101-2021_01_07_425675 143 5 copyright copyright NN 10_1101-2021_01_07_425675 143 6 holder holder NN 10_1101-2021_01_07_425675 143 7 for for IN 10_1101-2021_01_07_425675 143 8 this this DT 10_1101-2021_01_07_425675 143 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 143 10 version version NN 10_1101-2021_01_07_425675 143 11 posted post VBD 10_1101-2021_01_07_425675 143 12 January January NNP 10_1101-2021_01_07_425675 143 13 8 8 CD 10_1101-2021_01_07_425675 143 14 , , , 10_1101-2021_01_07_425675 143 15 2021 2021 CD 10_1101-2021_01_07_425675 143 16 . . . 10_1101-2021_01_07_425675 143 17 ; ; : 10_1101-2021_01_07_425675 143 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 143 19 : : : 10_1101-2021_01_07_425675 143 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 143 21 preprint preprint NN 10_1101-2021_01_07_425675 143 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 143 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 143 24 12 12 CD 10_1101-2021_01_07_425675 143 25 Revision Revision NNP 10_1101-2021_01_07_425675 143 26 of of IN 10_1101-2021_01_07_425675 143 27 the the DT 10_1101-2021_01_07_425675 143 28 anti anti JJ 10_1101-2021_01_07_425675 143 29 - - JJ 10_1101-2021_01_07_425675 143 30 FLAG FLAG NNP 10_1101-2021_01_07_425675 143 31 - - HYPH 10_1101-2021_01_07_425675 143 32 M2 M2 NNP 10_1101-2021_01_07_425675 143 33 Fab Fab NNP 10_1101-2021_01_07_425675 143 34 crystal crystal NN 10_1101-2021_01_07_425675 143 35 structure structure NN 10_1101-2021_01_07_425675 143 36 model model NN 10_1101-2021_01_07_425675 143 37 279 279 CD 10_1101-2021_01_07_425675 143 38 As as IN 10_1101-2021_01_07_425675 143 39 a a DT 10_1101-2021_01_07_425675 143 40 starting starting NN 10_1101-2021_01_07_425675 143 41 point point NN 10_1101-2021_01_07_425675 143 42 for for IN 10_1101-2021_01_07_425675 143 43 model model NN 10_1101-2021_01_07_425675 143 44 building building NN 10_1101-2021_01_07_425675 143 45 , , , 10_1101-2021_01_07_425675 143 46 the the DT 10_1101-2021_01_07_425675 143 47 reflection reflection NN 10_1101-2021_01_07_425675 143 48 file file NN 10_1101-2021_01_07_425675 143 49 and and CC 10_1101-2021_01_07_425675 143 50 coordinates coordinate NNS 10_1101-2021_01_07_425675 143 51 of of IN 10_1101-2021_01_07_425675 143 52 the the DT 10_1101-2021_01_07_425675 143 53 published publish VBN 10_1101-2021_01_07_425675 143 54 anti-280 anti-280 PRP$ 10_1101-2021_01_07_425675 143 55 FLAG FLAG NNP 10_1101-2021_01_07_425675 143 56 - - HYPH 10_1101-2021_01_07_425675 143 57 M2 M2 NNP 10_1101-2021_01_07_425675 143 58 Fab Fab NNP 10_1101-2021_01_07_425675 143 59 crystal crystal NN 10_1101-2021_01_07_425675 143 60 structure structure NN 10_1101-2021_01_07_425675 143 61 were be VBD 10_1101-2021_01_07_425675 143 62 used use VBN 10_1101-2021_01_07_425675 143 63 ( ( -LRB- 10_1101-2021_01_07_425675 143 64 PDB PDB NNP 10_1101-2021_01_07_425675 143 65 ID ID NNP 10_1101-2021_01_07_425675 143 66 : : : 10_1101-2021_01_07_425675 143 67 2G60 2g60 LS 10_1101-2021_01_07_425675 143 68 ) ) -RRB- 10_1101-2021_01_07_425675 143 69 33 33 CD 10_1101-2021_01_07_425675 143 70 . . . 10_1101-2021_01_07_425675 144 1 Care care NN 10_1101-2021_01_07_425675 144 2 was be VBD 10_1101-2021_01_07_425675 144 3 taken take VBN 10_1101-2021_01_07_425675 144 4 to to TO 10_1101-2021_01_07_425675 144 5 use use VB 10_1101-2021_01_07_425675 144 6 the the DT 10_1101-2021_01_07_425675 144 7 original original JJ 10_1101-2021_01_07_425675 144 8 281 281 CD 10_1101-2021_01_07_425675 144 9 Rfree Rfree NNP 10_1101-2021_01_07_425675 144 10 labels label NNS 10_1101-2021_01_07_425675 144 11 of of IN 10_1101-2021_01_07_425675 144 12 the the DT 10_1101-2021_01_07_425675 144 13 deposited deposited JJ 10_1101-2021_01_07_425675 144 14 reflection reflection NN 10_1101-2021_01_07_425675 144 15 file file NN 10_1101-2021_01_07_425675 144 16 for for IN 10_1101-2021_01_07_425675 144 17 refinement refinement NN 10_1101-2021_01_07_425675 144 18 , , , 10_1101-2021_01_07_425675 144 19 so so IN 10_1101-2021_01_07_425675 144 20 as as IN 10_1101-2021_01_07_425675 144 21 not not RB 10_1101-2021_01_07_425675 144 22 to to TO 10_1101-2021_01_07_425675 144 23 introduce introduce VB 10_1101-2021_01_07_425675 144 24 extra extra JJ 10_1101-2021_01_07_425675 144 25 model model NN 10_1101-2021_01_07_425675 144 26 bias bias NN 10_1101-2021_01_07_425675 144 27 . . . 10_1101-2021_01_07_425675 145 1 282 282 CD 10_1101-2021_01_07_425675 145 2 Differential differential NN 10_1101-2021_01_07_425675 145 3 residues residue NNS 10_1101-2021_01_07_425675 145 4 between between IN 10_1101-2021_01_07_425675 145 5 this this DT 10_1101-2021_01_07_425675 145 6 structure structure NN 10_1101-2021_01_07_425675 145 7 and and CC 10_1101-2021_01_07_425675 145 8 our -PRON- PRP$ 10_1101-2021_01_07_425675 145 9 mass mass NN 10_1101-2021_01_07_425675 145 10 spectrometry spectrometry NN 10_1101-2021_01_07_425675 145 11 - - HYPH 10_1101-2021_01_07_425675 145 12 derived derive VBN 10_1101-2021_01_07_425675 145 13 anti anti JJ 10_1101-2021_01_07_425675 145 14 - - JJ 10_1101-2021_01_07_425675 145 15 FLAG FLAG NNP 10_1101-2021_01_07_425675 145 16 283 283 CD 10_1101-2021_01_07_425675 145 17 sequence sequence NN 10_1101-2021_01_07_425675 145 18 were be VBD 10_1101-2021_01_07_425675 145 19 manually manually RB 10_1101-2021_01_07_425675 145 20 mutated mutate VBN 10_1101-2021_01_07_425675 145 21 and and CC 10_1101-2021_01_07_425675 145 22 fitted fit VBN 10_1101-2021_01_07_425675 145 23 in in IN 10_1101-2021_01_07_425675 145 24 the the DT 10_1101-2021_01_07_425675 145 25 density density NN 10_1101-2021_01_07_425675 145 26 using use VBG 10_1101-2021_01_07_425675 145 27 Coot Coot NNP 10_1101-2021_01_07_425675 145 28 40 40 CD 10_1101-2021_01_07_425675 145 29 . . . 10_1101-2021_01_07_425675 146 1 Many many JJ 10_1101-2021_01_07_425675 146 2 spurious spurious JJ 10_1101-2021_01_07_425675 146 3 water water NN 10_1101-2021_01_07_425675 146 4 284 284 CD 10_1101-2021_01_07_425675 146 5 molecules molecule NNS 10_1101-2021_01_07_425675 146 6 that that WDT 10_1101-2021_01_07_425675 146 7 caused cause VBD 10_1101-2021_01_07_425675 146 8 severe severe JJ 10_1101-2021_01_07_425675 146 9 steric steric JJ 10_1101-2021_01_07_425675 146 10 clashes clash NNS 10_1101-2021_01_07_425675 146 11 in in IN 10_1101-2021_01_07_425675 146 12 the the DT 10_1101-2021_01_07_425675 146 13 original original JJ 10_1101-2021_01_07_425675 146 14 model model NN 10_1101-2021_01_07_425675 146 15 were be VBD 10_1101-2021_01_07_425675 146 16 also also RB 10_1101-2021_01_07_425675 146 17 manually manually RB 10_1101-2021_01_07_425675 146 18 removed remove VBN 10_1101-2021_01_07_425675 146 19 in in IN 10_1101-2021_01_07_425675 146 20 285 285 CD 10_1101-2021_01_07_425675 146 21 Coot Coot NNP 10_1101-2021_01_07_425675 146 22 . . . 10_1101-2021_01_07_425675 147 1 Densities density NNS 10_1101-2021_01_07_425675 147 2 for for IN 10_1101-2021_01_07_425675 147 3 two two CD 10_1101-2021_01_07_425675 147 4 sulfate sulfate NN 10_1101-2021_01_07_425675 147 5 and and CC 10_1101-2021_01_07_425675 147 6 one one CD 10_1101-2021_01_07_425675 147 7 chloride chloride NN 10_1101-2021_01_07_425675 147 8 ion ion NN 10_1101-2021_01_07_425675 147 9 were be VBD 10_1101-2021_01_07_425675 147 10 identified identify VBN 10_1101-2021_01_07_425675 147 11 and and CC 10_1101-2021_01_07_425675 147 12 built build VBN 10_1101-2021_01_07_425675 147 13 into into IN 10_1101-2021_01_07_425675 147 14 the the DT 10_1101-2021_01_07_425675 147 15 model model NN 10_1101-2021_01_07_425675 147 16 . . . 10_1101-2021_01_07_425675 148 1 The the DT 10_1101-2021_01_07_425675 148 2 286 286 CD 10_1101-2021_01_07_425675 148 3 original original JJ 10_1101-2021_01_07_425675 148 4 crystallization crystallization NN 10_1101-2021_01_07_425675 148 5 solution solution NN 10_1101-2021_01_07_425675 148 6 contained contain VBD 10_1101-2021_01_07_425675 148 7 0.1 0.1 CD 10_1101-2021_01_07_425675 148 8 M M NNP 10_1101-2021_01_07_425675 148 9 ammonium ammonium NN 10_1101-2021_01_07_425675 148 10 sulfate sulfate NN 10_1101-2021_01_07_425675 148 11 . . . 10_1101-2021_01_07_425675 149 1 Iterative iterative JJ 10_1101-2021_01_07_425675 149 2 cycles cycle NNS 10_1101-2021_01_07_425675 149 3 of of IN 10_1101-2021_01_07_425675 149 4 model model NN 10_1101-2021_01_07_425675 149 5 287 287 CD 10_1101-2021_01_07_425675 149 6 geometry geometry NN 10_1101-2021_01_07_425675 149 7 optimization optimization NN 10_1101-2021_01_07_425675 149 8 in in IN 10_1101-2021_01_07_425675 149 9 real real JJ 10_1101-2021_01_07_425675 149 10 space space NN 10_1101-2021_01_07_425675 149 11 in in IN 10_1101-2021_01_07_425675 149 12 Coot Coot NNP 10_1101-2021_01_07_425675 149 13 and and CC 10_1101-2021_01_07_425675 149 14 reciprocal reciprocal JJ 10_1101-2021_01_07_425675 149 15 space space NN 10_1101-2021_01_07_425675 149 16 refinement refinement NN 10_1101-2021_01_07_425675 149 17 by by IN 10_1101-2021_01_07_425675 149 18 Phenix Phenix NNP 10_1101-2021_01_07_425675 149 19 were be VBD 10_1101-2021_01_07_425675 149 20 used use VBN 10_1101-2021_01_07_425675 149 21 288 288 CD 10_1101-2021_01_07_425675 149 22 to to TO 10_1101-2021_01_07_425675 149 23 generate generate VB 10_1101-2021_01_07_425675 149 24 the the DT 10_1101-2021_01_07_425675 149 25 final final JJ 10_1101-2021_01_07_425675 149 26 model model NN 10_1101-2021_01_07_425675 149 27 , , , 10_1101-2021_01_07_425675 149 28 which which WDT 10_1101-2021_01_07_425675 149 29 was be VBD 10_1101-2021_01_07_425675 149 30 validated validate VBN 10_1101-2021_01_07_425675 149 31 with with IN 10_1101-2021_01_07_425675 149 32 Molprobity Molprobity NNP 10_1101-2021_01_07_425675 149 33 41 41 CD 10_1101-2021_01_07_425675 149 34 - - SYM 10_1101-2021_01_07_425675 149 35 42 42 CD 10_1101-2021_01_07_425675 149 36 . . . 10_1101-2021_01_07_425675 150 1 289 289 CD 10_1101-2021_01_07_425675 150 2 290 290 CD 10_1101-2021_01_07_425675 150 3 Cloning clone VBG 10_1101-2021_01_07_425675 150 4 and and CC 10_1101-2021_01_07_425675 150 5 expression expression NN 10_1101-2021_01_07_425675 150 6 of of IN 10_1101-2021_01_07_425675 150 7 synthetic synthetic JJ 10_1101-2021_01_07_425675 150 8 recombinant recombinant JJ 10_1101-2021_01_07_425675 150 9 anti anti JJ 10_1101-2021_01_07_425675 150 10 - - JJ 10_1101-2021_01_07_425675 150 11 FLAG FLAG NNP 10_1101-2021_01_07_425675 150 12 - - HYPH 10_1101-2021_01_07_425675 150 13 M2 M2 NNP 10_1101-2021_01_07_425675 150 14 291 291 CD 10_1101-2021_01_07_425675 150 15 To to TO 10_1101-2021_01_07_425675 150 16 recombinantly recombinantly RB 10_1101-2021_01_07_425675 150 17 express express VB 10_1101-2021_01_07_425675 150 18 full full JJ 10_1101-2021_01_07_425675 150 19 - - HYPH 10_1101-2021_01_07_425675 150 20 length length NN 10_1101-2021_01_07_425675 150 21 anti anti JJ 10_1101-2021_01_07_425675 150 22 - - JJ 10_1101-2021_01_07_425675 150 23 FLAG FLAG NNP 10_1101-2021_01_07_425675 150 24 - - HYPH 10_1101-2021_01_07_425675 150 25 M2 M2 NNP 10_1101-2021_01_07_425675 150 26 , , , 10_1101-2021_01_07_425675 150 27 the the DT 10_1101-2021_01_07_425675 150 28 proteomic proteomic JJ 10_1101-2021_01_07_425675 150 29 sequences sequence NNS 10_1101-2021_01_07_425675 150 30 of of IN 10_1101-2021_01_07_425675 150 31 both both CC 10_1101-2021_01_07_425675 150 32 the the DT 10_1101-2021_01_07_425675 150 33 light light JJ 10_1101-2021_01_07_425675 150 34 292 292 CD 10_1101-2021_01_07_425675 150 35 and and CC 10_1101-2021_01_07_425675 150 36 heavy heavy JJ 10_1101-2021_01_07_425675 150 37 chains chain NNS 10_1101-2021_01_07_425675 150 38 were be VBD 10_1101-2021_01_07_425675 150 39 reverse reverse JJ 10_1101-2021_01_07_425675 150 40 - - HYPH 10_1101-2021_01_07_425675 150 41 translated translate VBN 10_1101-2021_01_07_425675 150 42 and and CC 10_1101-2021_01_07_425675 150 43 codon codon NNP 10_1101-2021_01_07_425675 150 44 optimized optimize VBN 10_1101-2021_01_07_425675 150 45 for for IN 10_1101-2021_01_07_425675 150 46 expression expression NN 10_1101-2021_01_07_425675 150 47 in in IN 10_1101-2021_01_07_425675 150 48 human human JJ 10_1101-2021_01_07_425675 150 49 cells cell NNS 10_1101-2021_01_07_425675 150 50 293 293 CD 10_1101-2021_01_07_425675 150 51 using use VBG 10_1101-2021_01_07_425675 150 52 the the DT 10_1101-2021_01_07_425675 150 53 Integrated Integrated NNP 10_1101-2021_01_07_425675 150 54 DNA DNA NNP 10_1101-2021_01_07_425675 150 55 Technologies Technologies NNPS 10_1101-2021_01_07_425675 150 56 ( ( -LRB- 10_1101-2021_01_07_425675 150 57 IDT IDT NNP 10_1101-2021_01_07_425675 150 58 ) ) -RRB- 10_1101-2021_01_07_425675 150 59 web web NN 10_1101-2021_01_07_425675 150 60 tool tool NN 10_1101-2021_01_07_425675 150 61 ( ( -LRB- 10_1101-2021_01_07_425675 150 62 http://www.idtdna.com/CodonOpt http://www.idtdna.com/codonopt NN 10_1101-2021_01_07_425675 150 63 ) ) -RRB- 10_1101-2021_01_07_425675 150 64 43 43 CD 10_1101-2021_01_07_425675 150 65 . . . 10_1101-2021_01_07_425675 151 1 For for IN 10_1101-2021_01_07_425675 151 2 294 294 CD 10_1101-2021_01_07_425675 151 3 the the DT 10_1101-2021_01_07_425675 151 4 linker linker NN 10_1101-2021_01_07_425675 151 5 and and CC 10_1101-2021_01_07_425675 151 6 Fc Fc NNP 10_1101-2021_01_07_425675 151 7 region region NN 10_1101-2021_01_07_425675 151 8 of of IN 10_1101-2021_01_07_425675 151 9 the the DT 10_1101-2021_01_07_425675 151 10 heavy heavy JJ 10_1101-2021_01_07_425675 151 11 chain chain NN 10_1101-2021_01_07_425675 151 12 , , , 10_1101-2021_01_07_425675 151 13 the the DT 10_1101-2021_01_07_425675 151 14 standard standard JJ 10_1101-2021_01_07_425675 151 15 mouse mouse NN 10_1101-2021_01_07_425675 151 16 Ig Ig NNP 10_1101-2021_01_07_425675 151 17 gamma-1 gamma-1 NNP 10_1101-2021_01_07_425675 151 18 ( ( -LRB- 10_1101-2021_01_07_425675 151 19 IGHG1 IGHG1 NNP 10_1101-2021_01_07_425675 151 20 ) ) -RRB- 10_1101-2021_01_07_425675 151 21 amino amino NN 10_1101-2021_01_07_425675 151 22 acid acid NN 10_1101-2021_01_07_425675 151 23 295 295 CD 10_1101-2021_01_07_425675 151 24 sequence sequence NN 10_1101-2021_01_07_425675 151 25 ( ( -LRB- 10_1101-2021_01_07_425675 151 26 Uniprot Uniprot NNP 10_1101-2021_01_07_425675 151 27 P01868.1 P01868.1 NNP 10_1101-2021_01_07_425675 151 28 ) ) -RRB- 10_1101-2021_01_07_425675 151 29 was be VBD 10_1101-2021_01_07_425675 151 30 used use VBN 10_1101-2021_01_07_425675 151 31 . . . 10_1101-2021_01_07_425675 152 1 An an DT 10_1101-2021_01_07_425675 152 2 N n CD 10_1101-2021_01_07_425675 152 3 - - HYPH 10_1101-2021_01_07_425675 152 4 terminal terminal NN 10_1101-2021_01_07_425675 152 5 secretion secretion NN 10_1101-2021_01_07_425675 152 6 signal signal NN 10_1101-2021_01_07_425675 152 7 peptide peptide NNP 10_1101-2021_01_07_425675 152 8 derived derive VBN 10_1101-2021_01_07_425675 152 9 from from IN 10_1101-2021_01_07_425675 152 10 296 296 CD 10_1101-2021_01_07_425675 152 11 human human JJ 10_1101-2021_01_07_425675 152 12 IgG IgG NNP 10_1101-2021_01_07_425675 152 13 light light NN 10_1101-2021_01_07_425675 152 14 chain chain NN 10_1101-2021_01_07_425675 152 15 ( ( -LRB- 10_1101-2021_01_07_425675 152 16 MEAPAQLLFLLLLWLPDTTG MEAPAQLLFLLLLWLPDTTG NNP 10_1101-2021_01_07_425675 152 17 ) ) -RRB- 10_1101-2021_01_07_425675 152 18 was be VBD 10_1101-2021_01_07_425675 152 19 added add VBN 10_1101-2021_01_07_425675 152 20 to to IN 10_1101-2021_01_07_425675 152 21 the the DT 10_1101-2021_01_07_425675 152 22 N n NN 10_1101-2021_01_07_425675 152 23 - - HYPH 10_1101-2021_01_07_425675 152 24 termini termini NN 10_1101-2021_01_07_425675 152 25 of of IN 10_1101-2021_01_07_425675 152 26 both both CC 10_1101-2021_01_07_425675 152 27 heavy heavy JJ 10_1101-2021_01_07_425675 152 28 297 297 CD 10_1101-2021_01_07_425675 152 29 and and CC 10_1101-2021_01_07_425675 152 30 light light JJ 10_1101-2021_01_07_425675 152 31 chains chain NNS 10_1101-2021_01_07_425675 152 32 . . . 10_1101-2021_01_07_425675 153 1 BamHI BamHI NNP 10_1101-2021_01_07_425675 153 2 and and CC 10_1101-2021_01_07_425675 153 3 NotI NotI NNP 10_1101-2021_01_07_425675 153 4 restriction restriction NN 10_1101-2021_01_07_425675 153 5 sites site NNS 10_1101-2021_01_07_425675 153 6 were be VBD 10_1101-2021_01_07_425675 153 7 added add VBN 10_1101-2021_01_07_425675 153 8 to to IN 10_1101-2021_01_07_425675 153 9 the the DT 10_1101-2021_01_07_425675 153 10 5 5 CD 10_1101-2021_01_07_425675 153 11 ’ ' '' 10_1101-2021_01_07_425675 153 12 and and CC 10_1101-2021_01_07_425675 153 13 3 3 CD 10_1101-2021_01_07_425675 153 14 ’ ' '' 10_1101-2021_01_07_425675 153 15 ends end NNS 10_1101-2021_01_07_425675 153 16 of of IN 10_1101-2021_01_07_425675 153 17 the the DT 10_1101-2021_01_07_425675 153 18 coding code VBG 10_1101-2021_01_07_425675 153 19 298 298 CD 10_1101-2021_01_07_425675 153 20 regions region NNS 10_1101-2021_01_07_425675 153 21 , , , 10_1101-2021_01_07_425675 153 22 respectively respectively RB 10_1101-2021_01_07_425675 153 23 . . . 10_1101-2021_01_07_425675 154 1 Only only RB 10_1101-2021_01_07_425675 154 2 for for IN 10_1101-2021_01_07_425675 154 3 the the DT 10_1101-2021_01_07_425675 154 4 light light JJ 10_1101-2021_01_07_425675 154 5 chain chain NN 10_1101-2021_01_07_425675 154 6 , , , 10_1101-2021_01_07_425675 154 7 a a DT 10_1101-2021_01_07_425675 154 8 double double JJ 10_1101-2021_01_07_425675 154 9 stop stop NN 10_1101-2021_01_07_425675 154 10 codon codon NN 10_1101-2021_01_07_425675 154 11 was be VBD 10_1101-2021_01_07_425675 154 12 introduced introduce VBN 10_1101-2021_01_07_425675 154 13 at at IN 10_1101-2021_01_07_425675 154 14 the the DT 10_1101-2021_01_07_425675 154 15 3 3 CD 10_1101-2021_01_07_425675 154 16 ’ ' '' 10_1101-2021_01_07_425675 154 17 site site NN 10_1101-2021_01_07_425675 154 18 299 299 CD 10_1101-2021_01_07_425675 154 19 before before IN 10_1101-2021_01_07_425675 154 20 the the DT 10_1101-2021_01_07_425675 154 21 NotI NotI NNP 10_1101-2021_01_07_425675 154 22 restriction restriction NN 10_1101-2021_01_07_425675 154 23 site site NN 10_1101-2021_01_07_425675 154 24 . . . 10_1101-2021_01_07_425675 155 1 The the DT 10_1101-2021_01_07_425675 155 2 coding code VBG 10_1101-2021_01_07_425675 155 3 regions region NNS 10_1101-2021_01_07_425675 155 4 were be VBD 10_1101-2021_01_07_425675 155 5 subcloned subclone VBN 10_1101-2021_01_07_425675 155 6 using use VBG 10_1101-2021_01_07_425675 155 7 BamHI BamHI NNP 10_1101-2021_01_07_425675 155 8 and and CC 10_1101-2021_01_07_425675 155 9 NotI NotI NNP 10_1101-2021_01_07_425675 155 10 300 300 CD 10_1101-2021_01_07_425675 155 11 restriction restriction NN 10_1101-2021_01_07_425675 155 12 - - HYPH 10_1101-2021_01_07_425675 155 13 ligation ligation NN 10_1101-2021_01_07_425675 155 14 into into IN 10_1101-2021_01_07_425675 155 15 a a DT 10_1101-2021_01_07_425675 155 16 pRK5 pRK5 NNP 10_1101-2021_01_07_425675 155 17 expression expression NN 10_1101-2021_01_07_425675 155 18 vector vector NN 10_1101-2021_01_07_425675 155 19 with with IN 10_1101-2021_01_07_425675 155 20 a a DT 10_1101-2021_01_07_425675 155 21 C c NN 10_1101-2021_01_07_425675 155 22 - - HYPH 10_1101-2021_01_07_425675 155 23 terminal terminal JJ 10_1101-2021_01_07_425675 155 24 octahistidine octahistidine NN 10_1101-2021_01_07_425675 155 25 tag tag NN 10_1101-2021_01_07_425675 155 26 between between IN 10_1101-2021_01_07_425675 155 27 the the DT 10_1101-2021_01_07_425675 155 28 301 301 CD 10_1101-2021_01_07_425675 155 29 NotI NotI NNP 10_1101-2021_01_07_425675 155 30 site site NN 10_1101-2021_01_07_425675 155 31 and and CC 10_1101-2021_01_07_425675 155 32 a a DT 10_1101-2021_01_07_425675 155 33 double double JJ 10_1101-2021_01_07_425675 155 34 stop stop NN 10_1101-2021_01_07_425675 155 35 codon codon NNP 10_1101-2021_01_07_425675 155 36 3 3 CD 10_1101-2021_01_07_425675 155 37 ’ ' '' 10_1101-2021_01_07_425675 155 38 of of IN 10_1101-2021_01_07_425675 155 39 the the DT 10_1101-2021_01_07_425675 155 40 insert insert NN 10_1101-2021_01_07_425675 155 41 , , , 10_1101-2021_01_07_425675 155 42 so so IN 10_1101-2021_01_07_425675 155 43 that that IN 10_1101-2021_01_07_425675 155 44 only only RB 10_1101-2021_01_07_425675 155 45 the the DT 10_1101-2021_01_07_425675 155 46 heavy heavy JJ 10_1101-2021_01_07_425675 155 47 chain chain NN 10_1101-2021_01_07_425675 155 48 has have VBZ 10_1101-2021_01_07_425675 155 49 a a DT 10_1101-2021_01_07_425675 155 50 C C NNP 10_1101-2021_01_07_425675 155 51 - - HYPH 10_1101-2021_01_07_425675 155 52 terminal terminal JJ 10_1101-2021_01_07_425675 155 53 302 302 CD 10_1101-2021_01_07_425675 155 54 AAAHHHHHHHH AAAHHHHHHHH NNP 10_1101-2021_01_07_425675 155 55 sequence sequence NN 10_1101-2021_01_07_425675 155 56 for for IN 10_1101-2021_01_07_425675 155 57 Nickel nickel NN 10_1101-2021_01_07_425675 155 58 - - HYPH 10_1101-2021_01_07_425675 155 59 affinity affinity NN 10_1101-2021_01_07_425675 155 60 purification purification NN 10_1101-2021_01_07_425675 155 61 ( ( -LRB- 10_1101-2021_01_07_425675 155 62 the the DT 10_1101-2021_01_07_425675 155 63 triple triple JJ 10_1101-2021_01_07_425675 155 64 alanine alanine NN 10_1101-2021_01_07_425675 155 65 resulting result VBG 10_1101-2021_01_07_425675 155 66 from from IN 10_1101-2021_01_07_425675 155 67 the the DT 10_1101-2021_01_07_425675 155 68 NotI NotI NNP 10_1101-2021_01_07_425675 155 69 303 303 CD 10_1101-2021_01_07_425675 155 70 site site NN 10_1101-2021_01_07_425675 155 71 ) ) -RRB- 10_1101-2021_01_07_425675 155 72 . . . 10_1101-2021_01_07_425675 156 1 The the DT 10_1101-2021_01_07_425675 156 2 L51I l51i JJ 10_1101-2021_01_07_425675 156 3 correction correction NN 10_1101-2021_01_07_425675 156 4 in in IN 10_1101-2021_01_07_425675 156 5 the the DT 10_1101-2021_01_07_425675 156 6 heavy heavy JJ 10_1101-2021_01_07_425675 156 7 chain chain NN 10_1101-2021_01_07_425675 156 8 was be VBD 10_1101-2021_01_07_425675 156 9 introduced introduce VBN 10_1101-2021_01_07_425675 156 10 later later RB 10_1101-2021_01_07_425675 156 11 ( ( -LRB- 10_1101-2021_01_07_425675 156 12 after after IN 10_1101-2021_01_07_425675 156 13 observing observe VBG 10_1101-2021_01_07_425675 156 14 it -PRON- PRP 10_1101-2021_01_07_425675 156 15 in in IN 10_1101-2021_01_07_425675 156 16 the the DT 10_1101-2021_01_07_425675 156 17 crystal crystal NN 10_1101-2021_01_07_425675 156 18 304 304 CD 10_1101-2021_01_07_425675 156 19 structure structure NN 10_1101-2021_01_07_425675 156 20 ) ) -RRB- 10_1101-2021_01_07_425675 156 21 by by IN 10_1101-2021_01_07_425675 156 22 IVA IVA NNP 10_1101-2021_01_07_425675 156 23 cloning clone VBG 10_1101-2021_01_07_425675 156 24 44 44 CD 10_1101-2021_01_07_425675 156 25 . . . 10_1101-2021_01_07_425675 157 1 Expression expression NN 10_1101-2021_01_07_425675 157 2 plasmids plasmid NNS 10_1101-2021_01_07_425675 157 3 for for IN 10_1101-2021_01_07_425675 157 4 the the DT 10_1101-2021_01_07_425675 157 5 heavy heavy JJ 10_1101-2021_01_07_425675 157 6 and and CC 10_1101-2021_01_07_425675 157 7 light light JJ 10_1101-2021_01_07_425675 157 8 chain chain NN 10_1101-2021_01_07_425675 157 9 were be VBD 10_1101-2021_01_07_425675 157 10 mixed mix VBN 10_1101-2021_01_07_425675 157 11 in in IN 10_1101-2021_01_07_425675 157 12 a a DT 10_1101-2021_01_07_425675 157 13 305 305 CD 10_1101-2021_01_07_425675 157 14 1:1 1:1 NNS 10_1101-2021_01_07_425675 157 15 ( ( -LRB- 10_1101-2021_01_07_425675 157 16 w w NNP 10_1101-2021_01_07_425675 157 17 / / SYM 10_1101-2021_01_07_425675 157 18 w w NNP 10_1101-2021_01_07_425675 157 19 ) ) -RRB- 10_1101-2021_01_07_425675 157 20 ratio ratio NN 10_1101-2021_01_07_425675 157 21 for for IN 10_1101-2021_01_07_425675 157 22 transient transient JJ 10_1101-2021_01_07_425675 157 23 transfection transfection NN 10_1101-2021_01_07_425675 157 24 in in IN 10_1101-2021_01_07_425675 157 25 HEK293 HEK293 NNP 10_1101-2021_01_07_425675 157 26 cells cell NNS 10_1101-2021_01_07_425675 157 27 with with IN 10_1101-2021_01_07_425675 157 28 polyethylenimine polyethylenimine NN 10_1101-2021_01_07_425675 157 29 , , , 10_1101-2021_01_07_425675 157 30 following follow VBG 10_1101-2021_01_07_425675 157 31 standard standard JJ 10_1101-2021_01_07_425675 157 32 306 306 CD 10_1101-2021_01_07_425675 157 33 procedures procedure NNS 10_1101-2021_01_07_425675 157 34 . . . 10_1101-2021_01_07_425675 158 1 Medium Medium NNP 10_1101-2021_01_07_425675 158 2 was be VBD 10_1101-2021_01_07_425675 158 3 collected collect VBN 10_1101-2021_01_07_425675 158 4 6 6 CD 10_1101-2021_01_07_425675 158 5 days day NNS 10_1101-2021_01_07_425675 158 6 after after IN 10_1101-2021_01_07_425675 158 7 transfection transfection NN 10_1101-2021_01_07_425675 158 8 and and CC 10_1101-2021_01_07_425675 158 9 cells cell NNS 10_1101-2021_01_07_425675 158 10 were be VBD 10_1101-2021_01_07_425675 158 11 spun spin VBN 10_1101-2021_01_07_425675 158 12 down down RP 10_1101-2021_01_07_425675 158 13 by by IN 10_1101-2021_01_07_425675 158 14 307 307 CD 10_1101-2021_01_07_425675 158 15 10 10 CD 10_1101-2021_01_07_425675 158 16     _SP 10_1101-2021_01_07_425675 158 17 minutes minute NNS 10_1101-2021_01_07_425675 158 18 of of IN 10_1101-2021_01_07_425675 158 19 centrifugation centrifugation NN 10_1101-2021_01_07_425675 158 20 at at IN 10_1101-2021_01_07_425675 158 21 1000 1000 CD 10_1101-2021_01_07_425675 158 22     _SP 10_1101-2021_01_07_425675 158 23 g. g. NNP 10_1101-2021_01_07_425675 158 24 Antibody Antibody NNP 10_1101-2021_01_07_425675 158 25 was be VBD 10_1101-2021_01_07_425675 158 26 directly directly RB 10_1101-2021_01_07_425675 158 27 purified purify VBN 10_1101-2021_01_07_425675 158 28 from from IN 10_1101-2021_01_07_425675 158 29 the the DT 10_1101-2021_01_07_425675 158 30 supernatant supernatant JJ 10_1101-2021_01_07_425675 158 31 using use VBG 10_1101-2021_01_07_425675 158 32 308 308 CD 10_1101-2021_01_07_425675 158 33 Ni Ni NNP 10_1101-2021_01_07_425675 158 34 - - HYPH 10_1101-2021_01_07_425675 158 35 sepharose sepharose JJ 10_1101-2021_01_07_425675 158 36 excel excel NNP 10_1101-2021_01_07_425675 158 37 resin resin NN 10_1101-2021_01_07_425675 158 38 ( ( -LRB- 10_1101-2021_01_07_425675 158 39 Cytiva Cytiva NNP 10_1101-2021_01_07_425675 158 40 Lifes Lifes NNP 10_1101-2021_01_07_425675 158 41 Sciences Sciences NNPS 10_1101-2021_01_07_425675 158 42 ) ) -RRB- 10_1101-2021_01_07_425675 158 43 , , , 10_1101-2021_01_07_425675 158 44 washing wash VBG 10_1101-2021_01_07_425675 158 45 with with IN 10_1101-2021_01_07_425675 158 46 500 500 CD 10_1101-2021_01_07_425675 158 47 mM mM NNP 10_1101-2021_01_07_425675 158 48 NaCl NaCl NNP 10_1101-2021_01_07_425675 158 49 , , , 10_1101-2021_01_07_425675 158 50 2 2 CD 10_1101-2021_01_07_425675 158 51 mM mm NN 10_1101-2021_01_07_425675 158 52 CaCl2 cacl2 NN 10_1101-2021_01_07_425675 158 53 , , , 10_1101-2021_01_07_425675 158 54 15 15 CD 10_1101-2021_01_07_425675 158 55 309 309 CD 10_1101-2021_01_07_425675 158 56 .CC .CC : 10_1101-2021_01_07_425675 158 57 - - : 10_1101-2021_01_07_425675 158 58 BY by IN 10_1101-2021_01_07_425675 158 59 4.0 4.0 CD 10_1101-2021_01_07_425675 158 60 International International NNP 10_1101-2021_01_07_425675 158 61 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 158 62 under under IN 10_1101-2021_01_07_425675 158 63 a a DT 10_1101-2021_01_07_425675 158 64 ( ( -LRB- 10_1101-2021_01_07_425675 158 65 which which WDT 10_1101-2021_01_07_425675 158 66 was be VBD 10_1101-2021_01_07_425675 158 67 not not RB 10_1101-2021_01_07_425675 158 68 certified certify VBN 10_1101-2021_01_07_425675 158 69 by by IN 10_1101-2021_01_07_425675 158 70 peer peer NN 10_1101-2021_01_07_425675 158 71 review review NN 10_1101-2021_01_07_425675 158 72 ) ) -RRB- 10_1101-2021_01_07_425675 158 73 is be VBZ 10_1101-2021_01_07_425675 158 74 the the DT 10_1101-2021_01_07_425675 158 75 author author NN 10_1101-2021_01_07_425675 158 76 / / SYM 10_1101-2021_01_07_425675 158 77 funder funder NN 10_1101-2021_01_07_425675 158 78 , , , 10_1101-2021_01_07_425675 158 79 who who WP 10_1101-2021_01_07_425675 158 80 has have VBZ 10_1101-2021_01_07_425675 158 81 granted grant VBN 10_1101-2021_01_07_425675 158 82 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 158 83 a a DT 10_1101-2021_01_07_425675 158 84 license license NN 10_1101-2021_01_07_425675 158 85 to to TO 10_1101-2021_01_07_425675 158 86 display display VB 10_1101-2021_01_07_425675 158 87 the the DT 10_1101-2021_01_07_425675 158 88 preprint preprint NN 10_1101-2021_01_07_425675 158 89 in in IN 10_1101-2021_01_07_425675 158 90 perpetuity perpetuity NN 10_1101-2021_01_07_425675 158 91 . . . 10_1101-2021_01_07_425675 159 1 It -PRON- PRP 10_1101-2021_01_07_425675 159 2 is be VBZ 10_1101-2021_01_07_425675 159 3 made make VBN 10_1101-2021_01_07_425675 159 4 The the DT 10_1101-2021_01_07_425675 159 5 copyright copyright NN 10_1101-2021_01_07_425675 159 6 holder holder NN 10_1101-2021_01_07_425675 159 7 for for IN 10_1101-2021_01_07_425675 159 8 this this DT 10_1101-2021_01_07_425675 159 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 159 10 version version NN 10_1101-2021_01_07_425675 159 11 posted post VBD 10_1101-2021_01_07_425675 159 12 January January NNP 10_1101-2021_01_07_425675 159 13 8 8 CD 10_1101-2021_01_07_425675 159 14 , , , 10_1101-2021_01_07_425675 159 15 2021 2021 CD 10_1101-2021_01_07_425675 159 16 . . . 10_1101-2021_01_07_425675 159 17 ; ; : 10_1101-2021_01_07_425675 159 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 159 19 : : : 10_1101-2021_01_07_425675 159 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 159 21 preprint preprint NN 10_1101-2021_01_07_425675 159 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 159 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ NNP 10_1101-2021_01_07_425675 159 24 13 13 CD 10_1101-2021_01_07_425675 159 25 mM mM NNP 10_1101-2021_01_07_425675 159 26 imidazole imidazole NN 10_1101-2021_01_07_425675 159 27 , , , 10_1101-2021_01_07_425675 159 28 20 20 CD 10_1101-2021_01_07_425675 159 29 mM mm NN 10_1101-2021_01_07_425675 159 30 HEPES hepe NNS 10_1101-2021_01_07_425675 159 31 pH ph NN 10_1101-2021_01_07_425675 159 32 7.8 7.8 CD 10_1101-2021_01_07_425675 159 33 and and CC 10_1101-2021_01_07_425675 159 34 eluting elute VBG 10_1101-2021_01_07_425675 159 35 with with IN 10_1101-2021_01_07_425675 159 36 500 500 CD 10_1101-2021_01_07_425675 159 37 mM mM NNP 10_1101-2021_01_07_425675 159 38 NaCl NaCl NNP 10_1101-2021_01_07_425675 159 39 , , , 10_1101-2021_01_07_425675 159 40 2 2 CD 10_1101-2021_01_07_425675 159 41 mM mm NN 10_1101-2021_01_07_425675 159 42 CaCl2 cacl2 NN 10_1101-2021_01_07_425675 159 43 , , , 10_1101-2021_01_07_425675 159 44 200 200 CD 10_1101-2021_01_07_425675 159 45 mM mM NNP 10_1101-2021_01_07_425675 159 46 310 310 CD 10_1101-2021_01_07_425675 159 47 imidazole imidazole NN 10_1101-2021_01_07_425675 159 48 , , , 10_1101-2021_01_07_425675 159 49 20 20 CD 10_1101-2021_01_07_425675 159 50 mM mm NN 10_1101-2021_01_07_425675 159 51 HEPES hepe NNS 10_1101-2021_01_07_425675 159 52 pH pH NNP 10_1101-2021_01_07_425675 159 53 7.8 7.8 CD 10_1101-2021_01_07_425675 159 54 . . . 10_1101-2021_01_07_425675 160 1 311 311 CD 10_1101-2021_01_07_425675 160 2 312 312 CD 10_1101-2021_01_07_425675 160 3 Western western JJ 10_1101-2021_01_07_425675 160 4 blot blot NN 10_1101-2021_01_07_425675 160 5 validation validation NN 10_1101-2021_01_07_425675 160 6 of of IN 10_1101-2021_01_07_425675 160 7 anti anti JJ 10_1101-2021_01_07_425675 160 8 - - JJ 10_1101-2021_01_07_425675 160 9 FLAG FLAG NNP 10_1101-2021_01_07_425675 160 10 - - HYPH 10_1101-2021_01_07_425675 160 11 M2 M2 NNP 10_1101-2021_01_07_425675 160 12 binding bind VBG 10_1101-2021_01_07_425675 160 13 313 313 CD 10_1101-2021_01_07_425675 160 14 To to TO 10_1101-2021_01_07_425675 160 15 test test VB 10_1101-2021_01_07_425675 160 16 binding bind VBG 10_1101-2021_01_07_425675 160 17 of of IN 10_1101-2021_01_07_425675 160 18 our -PRON- PRP$ 10_1101-2021_01_07_425675 160 19 recombinant recombinant JJ 10_1101-2021_01_07_425675 160 20 anti anti JJ 10_1101-2021_01_07_425675 160 21 - - JJ 10_1101-2021_01_07_425675 160 22 FLAG FLAG NNP 10_1101-2021_01_07_425675 160 23 - - HYPH 10_1101-2021_01_07_425675 160 24 M2 m2 NN 10_1101-2021_01_07_425675 160 25 to to IN 10_1101-2021_01_07_425675 160 26 the the DT 10_1101-2021_01_07_425675 160 27 FLAG FLAG NNP 10_1101-2021_01_07_425675 160 28 - - HYPH 10_1101-2021_01_07_425675 160 29 tag tag NN 10_1101-2021_01_07_425675 160 30 epitope epitope NN 10_1101-2021_01_07_425675 160 31 , , , 10_1101-2021_01_07_425675 160 32 compared compare VBN 10_1101-2021_01_07_425675 160 33 to to IN 10_1101-2021_01_07_425675 160 34 the the DT 10_1101-2021_01_07_425675 160 35 314 314 CD 10_1101-2021_01_07_425675 160 36 commercially commercially RB 10_1101-2021_01_07_425675 160 37 available available JJ 10_1101-2021_01_07_425675 160 38 anti anti JJ 10_1101-2021_01_07_425675 160 39 - - JJ 10_1101-2021_01_07_425675 160 40 FLAG FLAG NNP 10_1101-2021_01_07_425675 160 41 - - HYPH 10_1101-2021_01_07_425675 160 42 M2 M2 NNP 10_1101-2021_01_07_425675 160 43 ( ( -LRB- 10_1101-2021_01_07_425675 160 44 Sigma Sigma NNP 10_1101-2021_01_07_425675 160 45 ) ) -RRB- 10_1101-2021_01_07_425675 160 46 , , , 10_1101-2021_01_07_425675 160 47 we -PRON- PRP 10_1101-2021_01_07_425675 160 48 used use VBD 10_1101-2021_01_07_425675 160 49 both both DT 10_1101-2021_01_07_425675 160 50 antibodies antibody NNS 10_1101-2021_01_07_425675 160 51 to to TO 10_1101-2021_01_07_425675 160 52 probe probe VB 10_1101-2021_01_07_425675 160 53 Western western JJ 10_1101-2021_01_07_425675 160 54 blots blot NNS 10_1101-2021_01_07_425675 160 55 315 315 CD 10_1101-2021_01_07_425675 160 56 of of IN 10_1101-2021_01_07_425675 160 57 a a DT 10_1101-2021_01_07_425675 160 58 FLAG FLAG NNP 10_1101-2021_01_07_425675 160 59 - - HYPH 10_1101-2021_01_07_425675 160 60 tagged tag VBN 10_1101-2021_01_07_425675 160 61 protein protein NN 10_1101-2021_01_07_425675 160 62 in in IN 10_1101-2021_01_07_425675 160 63 parallel parallel NN 10_1101-2021_01_07_425675 160 64 . . . 10_1101-2021_01_07_425675 161 1 Purified Purified NNP 10_1101-2021_01_07_425675 161 2 Rabies Rabies NNPS 10_1101-2021_01_07_425675 161 3 virus virus NN 10_1101-2021_01_07_425675 161 4 glycoprotein glycoprotein NN 10_1101-2021_01_07_425675 161 5 ectodomain ectodomain NN 10_1101-2021_01_07_425675 161 6 ( ( -LRB- 10_1101-2021_01_07_425675 161 7 SAD SAD NNP 10_1101-2021_01_07_425675 161 8 B19 B19 NNP 10_1101-2021_01_07_425675 161 9 316 316 CD 10_1101-2021_01_07_425675 161 10 strain strain NN 10_1101-2021_01_07_425675 161 11 , , , 10_1101-2021_01_07_425675 161 12 UNIPROT UNIPROT NNP 10_1101-2021_01_07_425675 161 13 residues residue VBZ 10_1101-2021_01_07_425675 161 14 20 20 CD 10_1101-2021_01_07_425675 161 15 - - SYM 10_1101-2021_01_07_425675 161 16 450 450 CD 10_1101-2021_01_07_425675 161 17 ) ) -RRB- 10_1101-2021_01_07_425675 161 18 with with IN 10_1101-2021_01_07_425675 161 19 or or CC 10_1101-2021_01_07_425675 161 20 without without IN 10_1101-2021_01_07_425675 161 21 a a DT 10_1101-2021_01_07_425675 161 22 C c NN 10_1101-2021_01_07_425675 161 23 - - HYPH 10_1101-2021_01_07_425675 161 24 terminal terminal JJ 10_1101-2021_01_07_425675 161 25 FLAG flag NN 10_1101-2021_01_07_425675 161 26 - - HYPH 10_1101-2021_01_07_425675 161 27 tag tag NN 10_1101-2021_01_07_425675 161 28 followed follow VBN 10_1101-2021_01_07_425675 161 29 by by IN 10_1101-2021_01_07_425675 161 30 a a DT 10_1101-2021_01_07_425675 161 31 foldon foldon JJ 10_1101-2021_01_07_425675 161 32 317 317 CD 10_1101-2021_01_07_425675 161 33 trimerization trimerization NN 10_1101-2021_01_07_425675 161 34 domain domain NN 10_1101-2021_01_07_425675 161 35 and and CC 10_1101-2021_01_07_425675 161 36 an an DT 10_1101-2021_01_07_425675 161 37 octahistidine octahistidine NN 10_1101-2021_01_07_425675 161 38 tag tag NN 10_1101-2021_01_07_425675 161 39 was be VBD 10_1101-2021_01_07_425675 161 40 heated heat VBN 10_1101-2021_01_07_425675 161 41 to to IN 10_1101-2021_01_07_425675 161 42 95 95 CD 10_1101-2021_01_07_425675 161 43 ° ° , 10_1101-2021_01_07_425675 161 44 C C NNP 10_1101-2021_01_07_425675 161 45 in in IN 10_1101-2021_01_07_425675 161 46 XT XT NNP 10_1101-2021_01_07_425675 161 47 sample sample NN 10_1101-2021_01_07_425675 161 48 buffer buffer NN 10_1101-2021_01_07_425675 161 49 ( ( -LRB- 10_1101-2021_01_07_425675 161 50 Biorad Biorad NNP 10_1101-2021_01_07_425675 161 51 ) ) -RRB- 10_1101-2021_01_07_425675 161 52 318 318 CD 10_1101-2021_01_07_425675 161 53 for for IN 10_1101-2021_01_07_425675 161 54 5 5 CD 10_1101-2021_01_07_425675 161 55 minutes minute NNS 10_1101-2021_01_07_425675 161 56 . . . 10_1101-2021_01_07_425675 162 1 Samples sample NNS 10_1101-2021_01_07_425675 162 2 were be VBD 10_1101-2021_01_07_425675 162 3 run run VBN 10_1101-2021_01_07_425675 162 4 twice twice RB 10_1101-2021_01_07_425675 162 5 on on IN 10_1101-2021_01_07_425675 162 6 a a DT 10_1101-2021_01_07_425675 162 7 Criterion Criterion NNP 10_1101-2021_01_07_425675 162 8 XT XT NNP 10_1101-2021_01_07_425675 162 9 4 4 CD 10_1101-2021_01_07_425675 162 10 - - SYM 10_1101-2021_01_07_425675 162 11 12 12 CD 10_1101-2021_01_07_425675 162 12 % % NN 10_1101-2021_01_07_425675 162 13 polyacrylamide polyacrylamide NN 10_1101-2021_01_07_425675 162 14 gel gel NN 10_1101-2021_01_07_425675 162 15 ( ( -LRB- 10_1101-2021_01_07_425675 162 16 Biorad Biorad NNP 10_1101-2021_01_07_425675 162 17 ) ) -RRB- 10_1101-2021_01_07_425675 162 18 in in IN 10_1101-2021_01_07_425675 162 19 319 319 CD 10_1101-2021_01_07_425675 162 20 MES MES NNP 10_1101-2021_01_07_425675 162 21 XT XT NNP 10_1101-2021_01_07_425675 162 22 buffer buffer NN 10_1101-2021_01_07_425675 162 23 ( ( -LRB- 10_1101-2021_01_07_425675 162 24 Biorad Biorad NNP 10_1101-2021_01_07_425675 162 25 ) ) -RRB- 10_1101-2021_01_07_425675 162 26 before before IN 10_1101-2021_01_07_425675 162 27 Western western JJ 10_1101-2021_01_07_425675 162 28 blot blot NN 10_1101-2021_01_07_425675 162 29 transfer transfer VBP 10_1101-2021_01_07_425675 162 30 to to IN 10_1101-2021_01_07_425675 162 31 a a DT 10_1101-2021_01_07_425675 162 32 nitrocellulose nitrocellulose NN 10_1101-2021_01_07_425675 162 33 membrane membrane NN 10_1101-2021_01_07_425675 162 34 in in IN 10_1101-2021_01_07_425675 162 35 tris tris NNP 10_1101-2021_01_07_425675 162 36 - - HYPH 10_1101-2021_01_07_425675 162 37 glycine glycine NNP 10_1101-2021_01_07_425675 162 38 320 320 CD 10_1101-2021_01_07_425675 162 39 buffer buffer NN 10_1101-2021_01_07_425675 162 40 ( ( -LRB- 10_1101-2021_01_07_425675 162 41 Biorad Biorad NNP 10_1101-2021_01_07_425675 162 42 ) ) -RRB- 10_1101-2021_01_07_425675 162 43 with with IN 10_1101-2021_01_07_425675 162 44 20 20 CD 10_1101-2021_01_07_425675 162 45 % % NN 10_1101-2021_01_07_425675 162 46 methanol methanol NN 10_1101-2021_01_07_425675 162 47 . . . 10_1101-2021_01_07_425675 163 1 The the DT 10_1101-2021_01_07_425675 163 2 membrane membrane NN 10_1101-2021_01_07_425675 163 3 was be VBD 10_1101-2021_01_07_425675 163 4 blocked block VBN 10_1101-2021_01_07_425675 163 5 with with IN 10_1101-2021_01_07_425675 163 6 5 5 CD 10_1101-2021_01_07_425675 163 7 % % NN 10_1101-2021_01_07_425675 163 8 ( ( -LRB- 10_1101-2021_01_07_425675 163 9 w w NNP 10_1101-2021_01_07_425675 163 10 / / SYM 10_1101-2021_01_07_425675 163 11 v v NNP 10_1101-2021_01_07_425675 163 12 ) ) -RRB- 10_1101-2021_01_07_425675 163 13 dry dry JJ 10_1101-2021_01_07_425675 163 14 non non JJ 10_1101-2021_01_07_425675 163 15 - - JJ 10_1101-2021_01_07_425675 163 16 fat fat JJ 10_1101-2021_01_07_425675 163 17 milk milk NN 10_1101-2021_01_07_425675 163 18 in in IN 10_1101-2021_01_07_425675 163 19 321 321 CD 10_1101-2021_01_07_425675 163 20 phosphate phosphate RB 10_1101-2021_01_07_425675 163 21 - - HYPH 10_1101-2021_01_07_425675 163 22 buffered buffer VBN 10_1101-2021_01_07_425675 163 23 saline saline NN 10_1101-2021_01_07_425675 163 24 ( ( -LRB- 10_1101-2021_01_07_425675 163 25 PBS PBS NNP 10_1101-2021_01_07_425675 163 26 ) ) -RRB- 10_1101-2021_01_07_425675 163 27 overnight overnight RB 10_1101-2021_01_07_425675 163 28 at at IN 10_1101-2021_01_07_425675 163 29 4 4 CD 10_1101-2021_01_07_425675 163 30 ° ° NNS 10_1101-2021_01_07_425675 163 31 C C NNP 10_1101-2021_01_07_425675 163 32 . . . 10_1101-2021_01_07_425675 164 1 The the DT 10_1101-2021_01_07_425675 164 2 membrane membrane NN 10_1101-2021_01_07_425675 164 3 was be VBD 10_1101-2021_01_07_425675 164 4 cut cut VBN 10_1101-2021_01_07_425675 164 5 in in IN 10_1101-2021_01_07_425675 164 6 two two CD 10_1101-2021_01_07_425675 164 7 ( ( -LRB- 10_1101-2021_01_07_425675 164 8 one one CD 10_1101-2021_01_07_425675 164 9 half half NN 10_1101-2021_01_07_425675 164 10 for for IN 10_1101-2021_01_07_425675 164 11 322 322 CD 10_1101-2021_01_07_425675 164 12 the the DT 10_1101-2021_01_07_425675 164 13 commercial commercial NN 10_1101-2021_01_07_425675 164 14 and and CC 10_1101-2021_01_07_425675 164 15 one one CD 10_1101-2021_01_07_425675 164 16 half half NN 10_1101-2021_01_07_425675 164 17 for for IN 10_1101-2021_01_07_425675 164 18 the the DT 10_1101-2021_01_07_425675 164 19 recombinant recombinant JJ 10_1101-2021_01_07_425675 164 20 anti anti JJ 10_1101-2021_01_07_425675 164 21 - - JJ 10_1101-2021_01_07_425675 164 22 FLAG FLAG NNP 10_1101-2021_01_07_425675 164 23 - - HYPH 10_1101-2021_01_07_425675 164 24 M2 m2 NN 10_1101-2021_01_07_425675 164 25 ) ) -RRB- 10_1101-2021_01_07_425675 164 26 and and CC 10_1101-2021_01_07_425675 164 27 each each DT 10_1101-2021_01_07_425675 164 28 half half NN 10_1101-2021_01_07_425675 164 29 was be VBD 10_1101-2021_01_07_425675 164 30 probed probe VBN 10_1101-2021_01_07_425675 164 31 with with IN 10_1101-2021_01_07_425675 164 32 323 323 CD 10_1101-2021_01_07_425675 164 33 either either CC 10_1101-2021_01_07_425675 164 34 commercial commercial NN 10_1101-2021_01_07_425675 164 35 ( ( -LRB- 10_1101-2021_01_07_425675 164 36 Sigma Sigma NNP 10_1101-2021_01_07_425675 164 37 ) ) -RRB- 10_1101-2021_01_07_425675 164 38 or or CC 10_1101-2021_01_07_425675 164 39 recombinant recombinant VB 10_1101-2021_01_07_425675 164 40 anti anti JJ 10_1101-2021_01_07_425675 164 41 - - JJ 10_1101-2021_01_07_425675 164 42 FLAG FLAG NNP 10_1101-2021_01_07_425675 164 43 - - HYPH 10_1101-2021_01_07_425675 164 44 M2 M2 NNP 10_1101-2021_01_07_425675 164 45 at at IN 10_1101-2021_01_07_425675 164 46 1 1 CD 10_1101-2021_01_07_425675 164 47 µg µg NN 10_1101-2021_01_07_425675 164 48 / / SYM 10_1101-2021_01_07_425675 164 49 mL mL NNP 10_1101-2021_01_07_425675 164 50 in in IN 10_1101-2021_01_07_425675 164 51 PBS PBS NNP 10_1101-2021_01_07_425675 164 52 for for IN 10_1101-2021_01_07_425675 164 53 45 45 CD 10_1101-2021_01_07_425675 164 54 minutes minute NNS 10_1101-2021_01_07_425675 164 55 . . . 10_1101-2021_01_07_425675 165 1 After after IN 10_1101-2021_01_07_425675 165 2 324 324 CD 10_1101-2021_01_07_425675 165 3 washing wash VBG 10_1101-2021_01_07_425675 165 4 three three CD 10_1101-2021_01_07_425675 165 5 times time NNS 10_1101-2021_01_07_425675 165 6 with with IN 10_1101-2021_01_07_425675 165 7 PBST PBST NNP 10_1101-2021_01_07_425675 165 8 ( ( -LRB- 10_1101-2021_01_07_425675 165 9 PBS PBS NNP 10_1101-2021_01_07_425675 165 10 with with IN 10_1101-2021_01_07_425675 165 11 0.1 0.1 CD 10_1101-2021_01_07_425675 165 12 % % NN 10_1101-2021_01_07_425675 165 13 v v NN 10_1101-2021_01_07_425675 165 14 / / SYM 10_1101-2021_01_07_425675 165 15 v v NN 10_1101-2021_01_07_425675 165 16 Tween20 Tween20 NNP 10_1101-2021_01_07_425675 165 17 ) ) -RRB- 10_1101-2021_01_07_425675 165 18 , , , 10_1101-2021_01_07_425675 165 19 polyclonal polyclonal JJ 10_1101-2021_01_07_425675 165 20 goat goat NNP 10_1101-2021_01_07_425675 165 21 anti anti JJ 10_1101-2021_01_07_425675 165 22 - - JJ 10_1101-2021_01_07_425675 165 23 mouse mouse NN 10_1101-2021_01_07_425675 165 24 fused fuse VBD 10_1101-2021_01_07_425675 165 25 325 325 CD 10_1101-2021_01_07_425675 165 26 to to TO 10_1101-2021_01_07_425675 165 27 horseradish horseradish VB 10_1101-2021_01_07_425675 165 28 peroxidase peroxidase NN 10_1101-2021_01_07_425675 165 29 ( ( -LRB- 10_1101-2021_01_07_425675 165 30 HRP HRP NNP 10_1101-2021_01_07_425675 165 31 ) ) -RRB- 10_1101-2021_01_07_425675 165 32 was be VBD 10_1101-2021_01_07_425675 165 33 used use VBN 10_1101-2021_01_07_425675 165 34 to to TO 10_1101-2021_01_07_425675 165 35 detect detect VB 10_1101-2021_01_07_425675 165 36 binding binding NN 10_1101-2021_01_07_425675 165 37 of of IN 10_1101-2021_01_07_425675 165 38 anti anti JJ 10_1101-2021_01_07_425675 165 39 - - JJ 10_1101-2021_01_07_425675 165 40 FLAG FLAG NNP 10_1101-2021_01_07_425675 165 41 - - HYPH 10_1101-2021_01_07_425675 165 42 M2 m2 NN 10_1101-2021_01_07_425675 165 43 to to IN 10_1101-2021_01_07_425675 165 44 the the DT 10_1101-2021_01_07_425675 165 45 FLAG FLAG NNP 10_1101-2021_01_07_425675 165 46 - - HYPH 10_1101-2021_01_07_425675 165 47 tagged tag VBN 10_1101-2021_01_07_425675 165 48 326 326 CD 10_1101-2021_01_07_425675 165 49 protein protein NN 10_1101-2021_01_07_425675 165 50 for for IN 10_1101-2021_01_07_425675 165 51 both both DT 10_1101-2021_01_07_425675 165 52 membranes membrane NNS 10_1101-2021_01_07_425675 165 53 . . . 10_1101-2021_01_07_425675 166 1 The the DT 10_1101-2021_01_07_425675 166 2 membranes membrane NNS 10_1101-2021_01_07_425675 166 3 were be VBD 10_1101-2021_01_07_425675 166 4 washed wash VBN 10_1101-2021_01_07_425675 166 5 three three CD 10_1101-2021_01_07_425675 166 6 more more JJR 10_1101-2021_01_07_425675 166 7 times time NNS 10_1101-2021_01_07_425675 166 8 with with IN 10_1101-2021_01_07_425675 166 9 PBST PBST NNP 10_1101-2021_01_07_425675 166 10 before before IN 10_1101-2021_01_07_425675 166 11 327 327 CD 10_1101-2021_01_07_425675 166 12 applying apply VBG 10_1101-2021_01_07_425675 166 13 enhanced enhanced JJ 10_1101-2021_01_07_425675 166 14 chemiluminescence chemiluminescence NN 10_1101-2021_01_07_425675 166 15 ( ( -LRB- 10_1101-2021_01_07_425675 166 16 ECL ECL NNP 10_1101-2021_01_07_425675 166 17 ; ; : 10_1101-2021_01_07_425675 166 18 Pierce pierce NN 10_1101-2021_01_07_425675 166 19 ) ) -RRB- 10_1101-2021_01_07_425675 166 20 reagent reagent VB 10_1101-2021_01_07_425675 166 21 to to TO 10_1101-2021_01_07_425675 166 22 image image VB 10_1101-2021_01_07_425675 166 23 the the DT 10_1101-2021_01_07_425675 166 24 blots blot NNS 10_1101-2021_01_07_425675 166 25 in in IN 10_1101-2021_01_07_425675 166 26 parallel parallel NN 10_1101-2021_01_07_425675 166 27 . . . 10_1101-2021_01_07_425675 167 1 328 328 CD 10_1101-2021_01_07_425675 167 2 329 329 CD 10_1101-2021_01_07_425675 167 3 Data datum NNS 10_1101-2021_01_07_425675 167 4 Availability availability NN 10_1101-2021_01_07_425675 167 5 330 330 CD 10_1101-2021_01_07_425675 167 6 The the DT 10_1101-2021_01_07_425675 167 7 raw raw JJ 10_1101-2021_01_07_425675 167 8 LC LC NNP 10_1101-2021_01_07_425675 167 9 - - HYPH 10_1101-2021_01_07_425675 167 10 MS MS NNP 10_1101-2021_01_07_425675 167 11 / / SYM 10_1101-2021_01_07_425675 167 12 MS MS NNP 10_1101-2021_01_07_425675 167 13 data datum NNS 10_1101-2021_01_07_425675 167 14 have have VBP 10_1101-2021_01_07_425675 167 15 been be VBN 10_1101-2021_01_07_425675 167 16 deposited deposit VBN 10_1101-2021_01_07_425675 167 17 to to IN 10_1101-2021_01_07_425675 167 18 the the DT 10_1101-2021_01_07_425675 167 19 ProteomeXchange ProteomeXchange NNP 10_1101-2021_01_07_425675 167 20 Consortium Consortium NNP 10_1101-2021_01_07_425675 167 21 via via IN 10_1101-2021_01_07_425675 167 22 the the DT 10_1101-2021_01_07_425675 167 23 331 331 CD 10_1101-2021_01_07_425675 167 24 PRIDE PRIDE NNP 10_1101-2021_01_07_425675 167 25 partner partner NN 10_1101-2021_01_07_425675 167 26 repository repository NN 10_1101-2021_01_07_425675 167 27 with with IN 10_1101-2021_01_07_425675 167 28 the the DT 10_1101-2021_01_07_425675 167 29 dataset dataset NN 10_1101-2021_01_07_425675 167 30 identifier identifier NN 10_1101-2021_01_07_425675 167 31 PXD023419 PXD023419 NNP 10_1101-2021_01_07_425675 167 32 . . . 10_1101-2021_01_07_425675 168 1 The the DT 10_1101-2021_01_07_425675 168 2 coordinates coordinate NNS 10_1101-2021_01_07_425675 168 3 and and CC 10_1101-2021_01_07_425675 168 4 reflection reflection NN 10_1101-2021_01_07_425675 168 5 332 332 CD 10_1101-2021_01_07_425675 168 6 file file NN 10_1101-2021_01_07_425675 168 7 with with IN 10_1101-2021_01_07_425675 168 8 phases phase NNS 10_1101-2021_01_07_425675 168 9 for for IN 10_1101-2021_01_07_425675 168 10 the the DT 10_1101-2021_01_07_425675 168 11 remodeled remodel VBN 10_1101-2021_01_07_425675 168 12 crystal crystal NN 10_1101-2021_01_07_425675 168 13 structure structure NN 10_1101-2021_01_07_425675 168 14 of of IN 10_1101-2021_01_07_425675 168 15 the the DT 10_1101-2021_01_07_425675 168 16 anti anti JJ 10_1101-2021_01_07_425675 168 17 - - JJ 10_1101-2021_01_07_425675 168 18 FLAG FLAG NNP 10_1101-2021_01_07_425675 168 19 - - HYPH 10_1101-2021_01_07_425675 168 20 M2 M2 NNP 10_1101-2021_01_07_425675 168 21 Fab Fab NNP 10_1101-2021_01_07_425675 168 22 have have VBP 10_1101-2021_01_07_425675 168 23 been be VBN 10_1101-2021_01_07_425675 168 24 deposited deposit VBN 10_1101-2021_01_07_425675 168 25 333 333 CD 10_1101-2021_01_07_425675 168 26 in in IN 10_1101-2021_01_07_425675 168 27 the the DT 10_1101-2021_01_07_425675 168 28 Protein Protein NNP 10_1101-2021_01_07_425675 168 29 Data Data NNPS 10_1101-2021_01_07_425675 168 30 Bank Bank NNP 10_1101-2021_01_07_425675 168 31 under under IN 10_1101-2021_01_07_425675 168 32 accession accession NN 10_1101-2021_01_07_425675 168 33 code code NN 10_1101-2021_01_07_425675 168 34 7BG1 7bg1 CD 10_1101-2021_01_07_425675 168 35 . . . 10_1101-2021_01_07_425675 169 1 334 334 CD 10_1101-2021_01_07_425675 169 2 335 335 CD 10_1101-2021_01_07_425675 169 3 Acknowledgements Acknowledgements NNPS 10_1101-2021_01_07_425675 169 4 336 336 CD 10_1101-2021_01_07_425675 169 5 Herceptin Herceptin NNP 10_1101-2021_01_07_425675 169 6 was be VBD 10_1101-2021_01_07_425675 169 7 a a DT 10_1101-2021_01_07_425675 169 8 kind kind JJ 10_1101-2021_01_07_425675 169 9 gift gift NN 10_1101-2021_01_07_425675 169 10 from from IN 10_1101-2021_01_07_425675 169 11 Roche Roche NNP 10_1101-2021_01_07_425675 169 12 ( ( -LRB- 10_1101-2021_01_07_425675 169 13 Penzberg Penzberg NNP 10_1101-2021_01_07_425675 169 14 , , , 10_1101-2021_01_07_425675 169 15 Germany Germany NNP 10_1101-2021_01_07_425675 169 16 ) ) -RRB- 10_1101-2021_01_07_425675 169 17 . . . 10_1101-2021_01_07_425675 170 1 We -PRON- PRP 10_1101-2021_01_07_425675 170 2 would would MD 10_1101-2021_01_07_425675 170 3 like like VB 10_1101-2021_01_07_425675 170 4 to to TO 10_1101-2021_01_07_425675 170 5 acknowledge acknowledge VB 10_1101-2021_01_07_425675 170 6 337 337 CD 10_1101-2021_01_07_425675 170 7 support support NN 10_1101-2021_01_07_425675 170 8 by by IN 10_1101-2021_01_07_425675 170 9 Protein Protein NNP 10_1101-2021_01_07_425675 170 10 Metrics Metrics NNPS 10_1101-2021_01_07_425675 170 11 Inc. Inc. NNP 10_1101-2021_01_07_425675 170 12 through through IN 10_1101-2021_01_07_425675 170 13 access access NN 10_1101-2021_01_07_425675 170 14 to to IN 10_1101-2021_01_07_425675 170 15 Supernovo Supernovo NNP 10_1101-2021_01_07_425675 170 16 software software NN 10_1101-2021_01_07_425675 170 17 and and CC 10_1101-2021_01_07_425675 170 18 helpful helpful JJ 10_1101-2021_01_07_425675 170 19 discussion discussion NN 10_1101-2021_01_07_425675 170 20 on on IN 10_1101-2021_01_07_425675 170 21 338 338 CD 10_1101-2021_01_07_425675 170 22 de de NNP 10_1101-2021_01_07_425675 170 23 novo novo NNP 10_1101-2021_01_07_425675 170 24 antibody antibody NNP 10_1101-2021_01_07_425675 170 25 sequencing sequencing NNP 10_1101-2021_01_07_425675 170 26 . . . 10_1101-2021_01_07_425675 171 1 We -PRON- PRP 10_1101-2021_01_07_425675 171 2 would would MD 10_1101-2021_01_07_425675 171 3 like like VB 10_1101-2021_01_07_425675 171 4 to to TO 10_1101-2021_01_07_425675 171 5 thank thank VB 10_1101-2021_01_07_425675 171 6 everyone everyone NN 10_1101-2021_01_07_425675 171 7 in in IN 10_1101-2021_01_07_425675 171 8 the the DT 10_1101-2021_01_07_425675 171 9 Biomolecular Biomolecular NNP 10_1101-2021_01_07_425675 171 10 Mass Mass NNP 10_1101-2021_01_07_425675 171 11 339 339 CD 10_1101-2021_01_07_425675 171 12 .CC .CC : 10_1101-2021_01_07_425675 171 13 - - : 10_1101-2021_01_07_425675 171 14 BY by IN 10_1101-2021_01_07_425675 171 15 4.0 4.0 CD 10_1101-2021_01_07_425675 171 16 International International NNP 10_1101-2021_01_07_425675 171 17 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 171 18 under under IN 10_1101-2021_01_07_425675 171 19 a a DT 10_1101-2021_01_07_425675 171 20 ( ( -LRB- 10_1101-2021_01_07_425675 171 21 which which WDT 10_1101-2021_01_07_425675 171 22 was be VBD 10_1101-2021_01_07_425675 171 23 not not RB 10_1101-2021_01_07_425675 171 24 certified certify VBN 10_1101-2021_01_07_425675 171 25 by by IN 10_1101-2021_01_07_425675 171 26 peer peer NN 10_1101-2021_01_07_425675 171 27 review review NN 10_1101-2021_01_07_425675 171 28 ) ) -RRB- 10_1101-2021_01_07_425675 171 29 is be VBZ 10_1101-2021_01_07_425675 171 30 the the DT 10_1101-2021_01_07_425675 171 31 author author NN 10_1101-2021_01_07_425675 171 32 / / SYM 10_1101-2021_01_07_425675 171 33 funder funder NN 10_1101-2021_01_07_425675 171 34 , , , 10_1101-2021_01_07_425675 171 35 who who WP 10_1101-2021_01_07_425675 171 36 has have VBZ 10_1101-2021_01_07_425675 171 37 granted grant VBN 10_1101-2021_01_07_425675 171 38 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 171 39 a a DT 10_1101-2021_01_07_425675 171 40 license license NN 10_1101-2021_01_07_425675 171 41 to to TO 10_1101-2021_01_07_425675 171 42 display display VB 10_1101-2021_01_07_425675 171 43 the the DT 10_1101-2021_01_07_425675 171 44 preprint preprint NN 10_1101-2021_01_07_425675 171 45 in in IN 10_1101-2021_01_07_425675 171 46 perpetuity perpetuity NN 10_1101-2021_01_07_425675 171 47 . . . 10_1101-2021_01_07_425675 172 1 It -PRON- PRP 10_1101-2021_01_07_425675 172 2 is be VBZ 10_1101-2021_01_07_425675 172 3 made make VBN 10_1101-2021_01_07_425675 172 4 The the DT 10_1101-2021_01_07_425675 172 5 copyright copyright NN 10_1101-2021_01_07_425675 172 6 holder holder NN 10_1101-2021_01_07_425675 172 7 for for IN 10_1101-2021_01_07_425675 172 8 this this DT 10_1101-2021_01_07_425675 172 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 172 10 version version NN 10_1101-2021_01_07_425675 172 11 posted post VBD 10_1101-2021_01_07_425675 172 12 January January NNP 10_1101-2021_01_07_425675 172 13 8 8 CD 10_1101-2021_01_07_425675 172 14 , , , 10_1101-2021_01_07_425675 172 15 2021 2021 CD 10_1101-2021_01_07_425675 172 16 . . . 10_1101-2021_01_07_425675 172 17 ; ; : 10_1101-2021_01_07_425675 172 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 172 19 : : : 10_1101-2021_01_07_425675 172 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 172 21 preprint preprint NN 10_1101-2021_01_07_425675 172 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 172 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 172 24 14 14 CD 10_1101-2021_01_07_425675 172 25 Spectrometry Spectrometry NNP 10_1101-2021_01_07_425675 172 26 and and CC 10_1101-2021_01_07_425675 172 27 Proteomics Proteomics NNP 10_1101-2021_01_07_425675 172 28 group group NN 10_1101-2021_01_07_425675 172 29 at at IN 10_1101-2021_01_07_425675 172 30 Utrecht Utrecht NNP 10_1101-2021_01_07_425675 172 31 University University NNP 10_1101-2021_01_07_425675 172 32 for for IN 10_1101-2021_01_07_425675 172 33 support support NN 10_1101-2021_01_07_425675 172 34 and and CC 10_1101-2021_01_07_425675 172 35 helpful helpful JJ 10_1101-2021_01_07_425675 172 36 discussions discussion NNS 10_1101-2021_01_07_425675 172 37 . . . 10_1101-2021_01_07_425675 173 1 340 340 CD 10_1101-2021_01_07_425675 173 2 This this DT 10_1101-2021_01_07_425675 173 3 research research NN 10_1101-2021_01_07_425675 173 4 was be VBD 10_1101-2021_01_07_425675 173 5 funded fund VBN 10_1101-2021_01_07_425675 173 6 by by IN 10_1101-2021_01_07_425675 173 7 the the DT 10_1101-2021_01_07_425675 173 8 Dutch Dutch NNP 10_1101-2021_01_07_425675 173 9 Research Research NNP 10_1101-2021_01_07_425675 173 10 Council Council NNP 10_1101-2021_01_07_425675 173 11 NWO NWO NNP 10_1101-2021_01_07_425675 173 12 Gravitation Gravitation NNP 10_1101-2021_01_07_425675 173 13 2013 2013 CD 10_1101-2021_01_07_425675 173 14 BOO BOO NNP 10_1101-2021_01_07_425675 173 15 , , , 10_1101-2021_01_07_425675 173 16 Institute Institute NNP 10_1101-2021_01_07_425675 173 17 341 341 CD 10_1101-2021_01_07_425675 173 18 for for IN 10_1101-2021_01_07_425675 173 19 Chemical Chemical NNP 10_1101-2021_01_07_425675 173 20 Immunology Immunology NNP 10_1101-2021_01_07_425675 173 21 ( ( -LRB- 10_1101-2021_01_07_425675 173 22 ICI ICI NNP 10_1101-2021_01_07_425675 173 23 ; ; : 10_1101-2021_01_07_425675 173 24 024.002.009 024.002.009 NNP 10_1101-2021_01_07_425675 173 25 ) ) -RRB- 10_1101-2021_01_07_425675 173 26 . . . 10_1101-2021_01_07_425675 174 1 342 342 CD 10_1101-2021_01_07_425675 174 2 343 343 CD 10_1101-2021_01_07_425675 174 3 Author author NN 10_1101-2021_01_07_425675 174 4 Contributions contribution NNS 10_1101-2021_01_07_425675 174 5 344 344 CD 10_1101-2021_01_07_425675 174 6 WP WP NNP 10_1101-2021_01_07_425675 174 7 and and CC 10_1101-2021_01_07_425675 174 8 JS JS NNP 10_1101-2021_01_07_425675 174 9 conceived conceive VBD 10_1101-2021_01_07_425675 174 10 of of IN 10_1101-2021_01_07_425675 174 11 the the DT 10_1101-2021_01_07_425675 174 12 project project NN 10_1101-2021_01_07_425675 174 13 . . . 10_1101-2021_01_07_425675 175 1 WP WP NNP 10_1101-2021_01_07_425675 175 2 carried carry VBD 10_1101-2021_01_07_425675 175 3 out out RP 10_1101-2021_01_07_425675 175 4 the the DT 10_1101-2021_01_07_425675 175 5 MS MS NNP 10_1101-2021_01_07_425675 175 6 experiments experiment NNS 10_1101-2021_01_07_425675 175 7 . . . 10_1101-2021_01_07_425675 176 1 WP WP NNP 10_1101-2021_01_07_425675 176 2 and and CC 10_1101-2021_01_07_425675 176 3 JS JS NNP 10_1101-2021_01_07_425675 176 4 analyzed analyze VBD 10_1101-2021_01_07_425675 176 5 345 345 CD 10_1101-2021_01_07_425675 176 6 the the DT 10_1101-2021_01_07_425675 176 7 MS MS NNP 10_1101-2021_01_07_425675 176 8 data datum NNS 10_1101-2021_01_07_425675 176 9 . . . 10_1101-2021_01_07_425675 177 1 MFP MFP NNP 10_1101-2021_01_07_425675 177 2 remodeled remodel VBD 10_1101-2021_01_07_425675 177 3 the the DT 10_1101-2021_01_07_425675 177 4 crystal crystal NN 10_1101-2021_01_07_425675 177 5 structure structure NN 10_1101-2021_01_07_425675 177 6 . . . 10_1101-2021_01_07_425675 178 1 MFP MFP NNP 10_1101-2021_01_07_425675 178 2 cloned clone VBD 10_1101-2021_01_07_425675 178 3 and and CC 10_1101-2021_01_07_425675 178 4 produced produce VBD 10_1101-2021_01_07_425675 178 5 the the DT 10_1101-2021_01_07_425675 178 6 synthetic synthetic JJ 10_1101-2021_01_07_425675 178 7 346 346 CD 10_1101-2021_01_07_425675 178 8 recombinant recombinant JJ 10_1101-2021_01_07_425675 178 9 antibody antibody NN 10_1101-2021_01_07_425675 178 10 and and CC 10_1101-2021_01_07_425675 178 11 carried carry VBD 10_1101-2021_01_07_425675 178 12 out out RP 10_1101-2021_01_07_425675 178 13 Western western JJ 10_1101-2021_01_07_425675 178 14 blotting blotting NN 10_1101-2021_01_07_425675 178 15 . . . 10_1101-2021_01_07_425675 179 1 JS JS NNP 10_1101-2021_01_07_425675 179 2 supervised supervise VBD 10_1101-2021_01_07_425675 179 3 the the DT 10_1101-2021_01_07_425675 179 4 project project NN 10_1101-2021_01_07_425675 179 5 . . . 10_1101-2021_01_07_425675 180 1 JS JS NNP 10_1101-2021_01_07_425675 180 2 wrote write VBD 10_1101-2021_01_07_425675 180 3 the the DT 10_1101-2021_01_07_425675 180 4 347 347 CD 10_1101-2021_01_07_425675 180 5 first first JJ 10_1101-2021_01_07_425675 180 6 draft draft NN 10_1101-2021_01_07_425675 180 7 and and CC 10_1101-2021_01_07_425675 180 8 all all DT 10_1101-2021_01_07_425675 180 9 authors author NNS 10_1101-2021_01_07_425675 180 10 contributed contribute VBD 10_1101-2021_01_07_425675 180 11 to to IN 10_1101-2021_01_07_425675 180 12 preparing prepare VBG 10_1101-2021_01_07_425675 180 13 the the DT 10_1101-2021_01_07_425675 180 14 final final JJ 10_1101-2021_01_07_425675 180 15 version version NN 10_1101-2021_01_07_425675 180 16 of of IN 10_1101-2021_01_07_425675 180 17 the the DT 10_1101-2021_01_07_425675 180 18 manuscript manuscript NN 10_1101-2021_01_07_425675 180 19 . . . 10_1101-2021_01_07_425675 181 1 348 348 CD 10_1101-2021_01_07_425675 181 2 349 349 CD 10_1101-2021_01_07_425675 181 3 Competing Competing NNP 10_1101-2021_01_07_425675 181 4 Interests Interests NNPS 10_1101-2021_01_07_425675 181 5 350 350 CD 10_1101-2021_01_07_425675 181 6 The the DT 10_1101-2021_01_07_425675 181 7 authors author NNS 10_1101-2021_01_07_425675 181 8 declare declare VBP 10_1101-2021_01_07_425675 181 9 no no DT 10_1101-2021_01_07_425675 181 10 competing compete VBG 10_1101-2021_01_07_425675 181 11 interests interest NNS 10_1101-2021_01_07_425675 181 12 351 351 CD 10_1101-2021_01_07_425675 181 13 352 352 CD 10_1101-2021_01_07_425675 181 14 References reference NNS 10_1101-2021_01_07_425675 181 15 353 353 CD 10_1101-2021_01_07_425675 181 16 1 1 CD 10_1101-2021_01_07_425675 181 17 . . . 10_1101-2021_01_07_425675 182 1 Tonegawa Tonegawa NNP 10_1101-2021_01_07_425675 182 2 , , , 10_1101-2021_01_07_425675 182 3 S. S. NNP 10_1101-2021_01_07_425675 182 4 , , , 10_1101-2021_01_07_425675 182 5 Somatic somatic JJ 10_1101-2021_01_07_425675 182 6 generation generation NN 10_1101-2021_01_07_425675 182 7 of of IN 10_1101-2021_01_07_425675 182 8 antibody antibody NN 10_1101-2021_01_07_425675 182 9 diversity diversity NN 10_1101-2021_01_07_425675 182 10 . . . 10_1101-2021_01_07_425675 183 1 Nature nature NN 10_1101-2021_01_07_425675 183 2 1983 1983 CD 10_1101-2021_01_07_425675 183 3 , , , 10_1101-2021_01_07_425675 183 4 302 302 CD 10_1101-2021_01_07_425675 183 5 ( ( -LRB- 10_1101-2021_01_07_425675 183 6 5909 5909 CD 10_1101-2021_01_07_425675 183 7 ) ) -RRB- 10_1101-2021_01_07_425675 183 8 , , , 10_1101-2021_01_07_425675 183 9 575 575 CD 10_1101-2021_01_07_425675 183 10 - - SYM 10_1101-2021_01_07_425675 183 11 354 354 CD 10_1101-2021_01_07_425675 183 12 581 581 CD 10_1101-2021_01_07_425675 183 13 . . . 10_1101-2021_01_07_425675 184 1 355 355 CD 10_1101-2021_01_07_425675 184 2 2 2 CD 10_1101-2021_01_07_425675 184 3 . . . 10_1101-2021_01_07_425675 185 1 Watson Watson NNP 10_1101-2021_01_07_425675 185 2 , , , 10_1101-2021_01_07_425675 185 3 C. C. NNP 10_1101-2021_01_07_425675 185 4 T. T. NNP 10_1101-2021_01_07_425675 185 5 ; ; : 10_1101-2021_01_07_425675 185 6 Glanville Glanville NNP 10_1101-2021_01_07_425675 185 7 , , , 10_1101-2021_01_07_425675 185 8 J. J. NNP 10_1101-2021_01_07_425675 185 9 ; ; : 10_1101-2021_01_07_425675 185 10 Marasco Marasco NNP 10_1101-2021_01_07_425675 185 11 , , , 10_1101-2021_01_07_425675 185 12 W. W. NNP 10_1101-2021_01_07_425675 185 13 A. A. NNP 10_1101-2021_01_07_425675 185 14 , , , 10_1101-2021_01_07_425675 185 15 The the DT 10_1101-2021_01_07_425675 185 16 individual individual NN 10_1101-2021_01_07_425675 185 17 and and CC 10_1101-2021_01_07_425675 185 18 population population NN 10_1101-2021_01_07_425675 185 19 genetics genetic NNS 10_1101-2021_01_07_425675 185 20 of of IN 10_1101-2021_01_07_425675 185 21 356 356 CD 10_1101-2021_01_07_425675 185 22 antibody antibody NN 10_1101-2021_01_07_425675 185 23 immunity immunity NN 10_1101-2021_01_07_425675 185 24 . . . 10_1101-2021_01_07_425675 186 1 Trends trend NNS 10_1101-2021_01_07_425675 186 2 in in IN 10_1101-2021_01_07_425675 186 3 immunology immunology NN 10_1101-2021_01_07_425675 186 4 2017 2017 CD 10_1101-2021_01_07_425675 186 5 , , , 10_1101-2021_01_07_425675 186 6 38 38 CD 10_1101-2021_01_07_425675 186 7 ( ( -LRB- 10_1101-2021_01_07_425675 186 8 7 7 CD 10_1101-2021_01_07_425675 186 9 ) ) -RRB- 10_1101-2021_01_07_425675 186 10 , , , 10_1101-2021_01_07_425675 186 11 459 459 CD 10_1101-2021_01_07_425675 186 12 - - SYM 10_1101-2021_01_07_425675 186 13 470 470 CD 10_1101-2021_01_07_425675 186 14 . . . 10_1101-2021_01_07_425675 187 1 357 357 CD 10_1101-2021_01_07_425675 187 2 3 3 CD 10_1101-2021_01_07_425675 187 3 . . . 10_1101-2021_01_07_425675 188 1 Carter Carter NNP 10_1101-2021_01_07_425675 188 2 , , , 10_1101-2021_01_07_425675 188 3 P. P. NNP 10_1101-2021_01_07_425675 188 4 J. J. NNP 10_1101-2021_01_07_425675 188 5 ; ; : 10_1101-2021_01_07_425675 188 6 Lazar Lazar NNP 10_1101-2021_01_07_425675 188 7 , , , 10_1101-2021_01_07_425675 188 8 G. G. NNP 10_1101-2021_01_07_425675 188 9 A. A. NNP 10_1101-2021_01_07_425675 188 10 , , , 10_1101-2021_01_07_425675 188 11 Next Next NNP 10_1101-2021_01_07_425675 188 12 generation generation NN 10_1101-2021_01_07_425675 188 13 antibody antibody NN 10_1101-2021_01_07_425675 188 14 drugs drug NNS 10_1101-2021_01_07_425675 188 15 : : : 10_1101-2021_01_07_425675 188 16 pursuit pursuit NN 10_1101-2021_01_07_425675 188 17 of of IN 10_1101-2021_01_07_425675 188 18 the'high the'high NNP 10_1101-2021_01_07_425675 188 19 - - HYPH 10_1101-2021_01_07_425675 188 20 hanging hang VBG 10_1101-2021_01_07_425675 188 21 358 358 CD 10_1101-2021_01_07_425675 188 22 fruit fruit NN 10_1101-2021_01_07_425675 188 23 ' ' '' 10_1101-2021_01_07_425675 188 24 . . . 10_1101-2021_01_07_425675 189 1 Nature Nature NNP 10_1101-2021_01_07_425675 189 2 Reviews Reviews NNPS 10_1101-2021_01_07_425675 189 3 Drug Drug NNP 10_1101-2021_01_07_425675 189 4 Discovery Discovery NNP 10_1101-2021_01_07_425675 189 5 2018 2018 CD 10_1101-2021_01_07_425675 189 6 , , , 10_1101-2021_01_07_425675 189 7 17 17 CD 10_1101-2021_01_07_425675 189 8 ( ( -LRB- 10_1101-2021_01_07_425675 189 9 3 3 CD 10_1101-2021_01_07_425675 189 10 ) ) -RRB- 10_1101-2021_01_07_425675 189 11 , , , 10_1101-2021_01_07_425675 189 12 197 197 CD 10_1101-2021_01_07_425675 189 13 . . . 10_1101-2021_01_07_425675 190 1 359 359 CD 10_1101-2021_01_07_425675 190 2 4 4 CD 10_1101-2021_01_07_425675 190 3 . . . 10_1101-2021_01_07_425675 191 1 Grilo Grilo NNP 10_1101-2021_01_07_425675 191 2 , , , 10_1101-2021_01_07_425675 191 3 A. A. NNP 10_1101-2021_01_07_425675 191 4 L. L. NNP 10_1101-2021_01_07_425675 191 5 ; ; : 10_1101-2021_01_07_425675 191 6 Mantalaris Mantalaris NNP 10_1101-2021_01_07_425675 191 7 , , , 10_1101-2021_01_07_425675 191 8 A. A. NNP 10_1101-2021_01_07_425675 191 9 , , , 10_1101-2021_01_07_425675 191 10 The the DT 10_1101-2021_01_07_425675 191 11 increasingly increasingly RB 10_1101-2021_01_07_425675 191 12 human human JJ 10_1101-2021_01_07_425675 191 13 and and CC 10_1101-2021_01_07_425675 191 14 profitable profitable JJ 10_1101-2021_01_07_425675 191 15 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 191 16 antibody antibody NN 10_1101-2021_01_07_425675 191 17 360 360 CD 10_1101-2021_01_07_425675 191 18 market market NN 10_1101-2021_01_07_425675 191 19 . . . 10_1101-2021_01_07_425675 192 1 Trends trend NNS 10_1101-2021_01_07_425675 192 2 in in IN 10_1101-2021_01_07_425675 192 3 biotechnology biotechnology NN 10_1101-2021_01_07_425675 192 4 2019 2019 CD 10_1101-2021_01_07_425675 192 5 , , , 10_1101-2021_01_07_425675 192 6 37 37 CD 10_1101-2021_01_07_425675 192 7 ( ( -LRB- 10_1101-2021_01_07_425675 192 8 1 1 CD 10_1101-2021_01_07_425675 192 9 ) ) -RRB- 10_1101-2021_01_07_425675 192 10 , , , 10_1101-2021_01_07_425675 192 11 9 9 CD 10_1101-2021_01_07_425675 192 12 - - SYM 10_1101-2021_01_07_425675 192 13 16 16 CD 10_1101-2021_01_07_425675 192 14 . . . 10_1101-2021_01_07_425675 193 1 361 361 CD 10_1101-2021_01_07_425675 193 2 5 5 CD 10_1101-2021_01_07_425675 193 3 . . . 10_1101-2021_01_07_425675 194 1 Baker Baker NNP 10_1101-2021_01_07_425675 194 2 , , , 10_1101-2021_01_07_425675 194 3 M. M. NNP 10_1101-2021_01_07_425675 194 4 , , , 10_1101-2021_01_07_425675 194 5 Blame blame VB 10_1101-2021_01_07_425675 194 6 it -PRON- PRP 10_1101-2021_01_07_425675 194 7 on on IN 10_1101-2021_01_07_425675 194 8 the the DT 10_1101-2021_01_07_425675 194 9 antibodies antibody NNS 10_1101-2021_01_07_425675 194 10 . . . 10_1101-2021_01_07_425675 195 1 Nature nature NN 10_1101-2021_01_07_425675 195 2 2015 2015 CD 10_1101-2021_01_07_425675 195 3 , , , 10_1101-2021_01_07_425675 195 4 521 521 CD 10_1101-2021_01_07_425675 195 5 ( ( -LRB- 10_1101-2021_01_07_425675 195 6 7552 7552 CD 10_1101-2021_01_07_425675 195 7 ) ) -RRB- 10_1101-2021_01_07_425675 195 8 , , , 10_1101-2021_01_07_425675 195 9 274 274 CD 10_1101-2021_01_07_425675 195 10 . . . 10_1101-2021_01_07_425675 196 1 362 362 CD 10_1101-2021_01_07_425675 196 2 6 6 CD 10_1101-2021_01_07_425675 196 3 . . . 10_1101-2021_01_07_425675 197 1 Uhlen Uhlen NNP 10_1101-2021_01_07_425675 197 2 , , , 10_1101-2021_01_07_425675 197 3 M. M. NNP 10_1101-2021_01_07_425675 197 4 ; ; : 10_1101-2021_01_07_425675 197 5 Bandrowski Bandrowski NNP 10_1101-2021_01_07_425675 197 6 , , , 10_1101-2021_01_07_425675 197 7 A. a. NN 10_1101-2021_01_07_425675 197 8 ; ; : 10_1101-2021_01_07_425675 197 9 Carr Carr NNP 10_1101-2021_01_07_425675 197 10 , , , 10_1101-2021_01_07_425675 197 11 S. S. NNP 10_1101-2021_01_07_425675 197 12 ; ; : 10_1101-2021_01_07_425675 197 13 Edwards Edwards NNP 10_1101-2021_01_07_425675 197 14 , , , 10_1101-2021_01_07_425675 197 15 A. a. NN 10_1101-2021_01_07_425675 197 16 ; ; : 10_1101-2021_01_07_425675 197 17 Ellenberg Ellenberg NNP 10_1101-2021_01_07_425675 197 18 , , , 10_1101-2021_01_07_425675 197 19 J. J. NNP 10_1101-2021_01_07_425675 197 20 ; ; : 10_1101-2021_01_07_425675 197 21 Lundberg Lundberg NNP 10_1101-2021_01_07_425675 197 22 , , , 10_1101-2021_01_07_425675 197 23 E. E. NNP 10_1101-2021_01_07_425675 197 24 ; ; : 10_1101-2021_01_07_425675 197 25 Rimm Rimm NNP 10_1101-2021_01_07_425675 197 26 , , , 10_1101-2021_01_07_425675 197 27 D. D. NNP 10_1101-2021_01_07_425675 197 28 363 363 CD 10_1101-2021_01_07_425675 197 29 L. L. NNP 10_1101-2021_01_07_425675 197 30 ; ; : 10_1101-2021_01_07_425675 197 31 Rodriguez Rodriguez NNP 10_1101-2021_01_07_425675 197 32 , , , 10_1101-2021_01_07_425675 197 33 H. H. NNP 10_1101-2021_01_07_425675 197 34 ; ; : 10_1101-2021_01_07_425675 197 35 Hiltke Hiltke NNP 10_1101-2021_01_07_425675 197 36 , , , 10_1101-2021_01_07_425675 197 37 T. T. NNP 10_1101-2021_01_07_425675 197 38 ; ; : 10_1101-2021_01_07_425675 197 39 Snyder Snyder NNP 10_1101-2021_01_07_425675 197 40 , , , 10_1101-2021_01_07_425675 197 41 M. M. NNP 10_1101-2021_01_07_425675 197 42 , , , 10_1101-2021_01_07_425675 197 43 A a DT 10_1101-2021_01_07_425675 197 44 proposal proposal NN 10_1101-2021_01_07_425675 197 45 for for IN 10_1101-2021_01_07_425675 197 46 validation validation NN 10_1101-2021_01_07_425675 197 47 of of IN 10_1101-2021_01_07_425675 197 48 antibodies antibody NNS 10_1101-2021_01_07_425675 197 49 . . . 10_1101-2021_01_07_425675 198 1 Nature nature NN 10_1101-2021_01_07_425675 198 2 methods method NNS 10_1101-2021_01_07_425675 198 3 364 364 CD 10_1101-2021_01_07_425675 198 4 2016 2016 CD 10_1101-2021_01_07_425675 198 5 , , , 10_1101-2021_01_07_425675 198 6 13 13 CD 10_1101-2021_01_07_425675 198 7 ( ( -LRB- 10_1101-2021_01_07_425675 198 8 10 10 CD 10_1101-2021_01_07_425675 198 9 ) ) -RRB- 10_1101-2021_01_07_425675 198 10 , , , 10_1101-2021_01_07_425675 198 11 823 823 CD 10_1101-2021_01_07_425675 198 12 - - SYM 10_1101-2021_01_07_425675 198 13 827 827 CD 10_1101-2021_01_07_425675 198 14 . . . 10_1101-2021_01_07_425675 199 1 365 365 CD 10_1101-2021_01_07_425675 199 2 7 7 CD 10_1101-2021_01_07_425675 199 3 . . . 10_1101-2021_01_07_425675 200 1 Fischer Fischer NNP 10_1101-2021_01_07_425675 200 2 , , , 10_1101-2021_01_07_425675 200 3 N. N. NNP 10_1101-2021_01_07_425675 200 4 In In NNP 10_1101-2021_01_07_425675 200 5 Sequencing Sequencing NNP 10_1101-2021_01_07_425675 200 6 antibody antibody NN 10_1101-2021_01_07_425675 200 7 repertoires repertoire VBZ 10_1101-2021_01_07_425675 200 8 : : : 10_1101-2021_01_07_425675 200 9 the the DT 10_1101-2021_01_07_425675 200 10 next next JJ 10_1101-2021_01_07_425675 200 11 generation generation NN 10_1101-2021_01_07_425675 200 12 , , , 10_1101-2021_01_07_425675 200 13 MAbs MAbs NNP 10_1101-2021_01_07_425675 200 14 , , , 10_1101-2021_01_07_425675 200 15 Taylor Taylor NNP 10_1101-2021_01_07_425675 200 16 & & CC 10_1101-2021_01_07_425675 200 17 366 366 CD 10_1101-2021_01_07_425675 200 18 Francis Francis NNP 10_1101-2021_01_07_425675 200 19 : : : 10_1101-2021_01_07_425675 200 20 2011 2011 CD 10_1101-2021_01_07_425675 200 21 ; ; : 10_1101-2021_01_07_425675 200 22 pp pp NNP 10_1101-2021_01_07_425675 200 23 17 17 CD 10_1101-2021_01_07_425675 200 24 - - SYM 10_1101-2021_01_07_425675 200 25 20 20 CD 10_1101-2021_01_07_425675 200 26 . . . 10_1101-2021_01_07_425675 201 1 367 367 CD 10_1101-2021_01_07_425675 201 2 8 8 CD 10_1101-2021_01_07_425675 201 3 . . . 10_1101-2021_01_07_425675 202 1 Georgiou Georgiou NNP 10_1101-2021_01_07_425675 202 2 , , , 10_1101-2021_01_07_425675 202 3 G. G. NNP 10_1101-2021_01_07_425675 202 4 ; ; : 10_1101-2021_01_07_425675 202 5 Ippolito Ippolito NNP 10_1101-2021_01_07_425675 202 6 , , , 10_1101-2021_01_07_425675 202 7 G. G. NNP 10_1101-2021_01_07_425675 202 8 C. C. NNP 10_1101-2021_01_07_425675 202 9 ; ; : 10_1101-2021_01_07_425675 202 10 Beausang Beausang NNP 10_1101-2021_01_07_425675 202 11 , , , 10_1101-2021_01_07_425675 202 12 J. J. NNP 10_1101-2021_01_07_425675 202 13 ; ; : 10_1101-2021_01_07_425675 202 14 Busse Busse NNP 10_1101-2021_01_07_425675 202 15 , , , 10_1101-2021_01_07_425675 202 16 C. C. NNP 10_1101-2021_01_07_425675 202 17 E. E. NNP 10_1101-2021_01_07_425675 202 18 ; ; : 10_1101-2021_01_07_425675 202 19 Wardemann Wardemann NNP 10_1101-2021_01_07_425675 202 20 , , , 10_1101-2021_01_07_425675 202 21 H. H. NNP 10_1101-2021_01_07_425675 202 22 ; ; : 10_1101-2021_01_07_425675 202 23 Quake Quake NNP 10_1101-2021_01_07_425675 202 24 , , , 10_1101-2021_01_07_425675 202 25 S. S. NNP 10_1101-2021_01_07_425675 202 26 R. R. NNP 10_1101-2021_01_07_425675 202 27 , , , 10_1101-2021_01_07_425675 202 28 368 368 CD 10_1101-2021_01_07_425675 202 29 The the DT 10_1101-2021_01_07_425675 202 30 promise promise NN 10_1101-2021_01_07_425675 202 31 and and CC 10_1101-2021_01_07_425675 202 32 challenge challenge NN 10_1101-2021_01_07_425675 202 33 of of IN 10_1101-2021_01_07_425675 202 34 high high JJ 10_1101-2021_01_07_425675 202 35 - - HYPH 10_1101-2021_01_07_425675 202 36 throughput throughput NN 10_1101-2021_01_07_425675 202 37 sequencing sequencing NN 10_1101-2021_01_07_425675 202 38 of of IN 10_1101-2021_01_07_425675 202 39 the the DT 10_1101-2021_01_07_425675 202 40 antibody antibody NN 10_1101-2021_01_07_425675 202 41 repertoire repertoire NN 10_1101-2021_01_07_425675 202 42 . . . 10_1101-2021_01_07_425675 203 1 Nature nature NN 10_1101-2021_01_07_425675 203 2 369 369 CD 10_1101-2021_01_07_425675 203 3 biotechnology biotechnology NN 10_1101-2021_01_07_425675 203 4 2014 2014 CD 10_1101-2021_01_07_425675 203 5 , , , 10_1101-2021_01_07_425675 203 6 32 32 CD 10_1101-2021_01_07_425675 203 7 ( ( -LRB- 10_1101-2021_01_07_425675 203 8 2 2 CD 10_1101-2021_01_07_425675 203 9 ) ) -RRB- 10_1101-2021_01_07_425675 203 10 , , , 10_1101-2021_01_07_425675 203 11 158 158 CD 10_1101-2021_01_07_425675 203 12 - - SYM 10_1101-2021_01_07_425675 203 13 168 168 CD 10_1101-2021_01_07_425675 203 14 . . . 10_1101-2021_01_07_425675 204 1 370 370 CD 10_1101-2021_01_07_425675 204 2 .CC .CC : 10_1101-2021_01_07_425675 204 3 - - : 10_1101-2021_01_07_425675 204 4 BY by IN 10_1101-2021_01_07_425675 204 5 4.0 4.0 CD 10_1101-2021_01_07_425675 204 6 International International NNP 10_1101-2021_01_07_425675 204 7 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 204 8 under under IN 10_1101-2021_01_07_425675 204 9 a a DT 10_1101-2021_01_07_425675 204 10 ( ( -LRB- 10_1101-2021_01_07_425675 204 11 which which WDT 10_1101-2021_01_07_425675 204 12 was be VBD 10_1101-2021_01_07_425675 204 13 not not RB 10_1101-2021_01_07_425675 204 14 certified certify VBN 10_1101-2021_01_07_425675 204 15 by by IN 10_1101-2021_01_07_425675 204 16 peer peer NN 10_1101-2021_01_07_425675 204 17 review review NN 10_1101-2021_01_07_425675 204 18 ) ) -RRB- 10_1101-2021_01_07_425675 204 19 is be VBZ 10_1101-2021_01_07_425675 204 20 the the DT 10_1101-2021_01_07_425675 204 21 author author NN 10_1101-2021_01_07_425675 204 22 / / SYM 10_1101-2021_01_07_425675 204 23 funder funder NN 10_1101-2021_01_07_425675 204 24 , , , 10_1101-2021_01_07_425675 204 25 who who WP 10_1101-2021_01_07_425675 204 26 has have VBZ 10_1101-2021_01_07_425675 204 27 granted grant VBN 10_1101-2021_01_07_425675 204 28 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 204 29 a a DT 10_1101-2021_01_07_425675 204 30 license license NN 10_1101-2021_01_07_425675 204 31 to to TO 10_1101-2021_01_07_425675 204 32 display display VB 10_1101-2021_01_07_425675 204 33 the the DT 10_1101-2021_01_07_425675 204 34 preprint preprint NN 10_1101-2021_01_07_425675 204 35 in in IN 10_1101-2021_01_07_425675 204 36 perpetuity perpetuity NN 10_1101-2021_01_07_425675 204 37 . . . 10_1101-2021_01_07_425675 205 1 It -PRON- PRP 10_1101-2021_01_07_425675 205 2 is be VBZ 10_1101-2021_01_07_425675 205 3 made make VBN 10_1101-2021_01_07_425675 205 4 The the DT 10_1101-2021_01_07_425675 205 5 copyright copyright NN 10_1101-2021_01_07_425675 205 6 holder holder NN 10_1101-2021_01_07_425675 205 7 for for IN 10_1101-2021_01_07_425675 205 8 this this DT 10_1101-2021_01_07_425675 205 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 205 10 version version NN 10_1101-2021_01_07_425675 205 11 posted post VBD 10_1101-2021_01_07_425675 205 12 January January NNP 10_1101-2021_01_07_425675 205 13 8 8 CD 10_1101-2021_01_07_425675 205 14 , , , 10_1101-2021_01_07_425675 205 15 2021 2021 CD 10_1101-2021_01_07_425675 205 16 . . . 10_1101-2021_01_07_425675 205 17 ; ; : 10_1101-2021_01_07_425675 205 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 205 19 : : : 10_1101-2021_01_07_425675 205 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 205 21 preprint preprint NN 10_1101-2021_01_07_425675 205 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 205 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ NNP 10_1101-2021_01_07_425675 205 24 15 15 CD 10_1101-2021_01_07_425675 205 25 9 9 CD 10_1101-2021_01_07_425675 205 26 . . . 10_1101-2021_01_07_425675 206 1 Robinson Robinson NNP 10_1101-2021_01_07_425675 206 2 , , , 10_1101-2021_01_07_425675 206 3 W. W. NNP 10_1101-2021_01_07_425675 206 4 H. H. NNP 10_1101-2021_01_07_425675 206 5 , , , 10_1101-2021_01_07_425675 206 6 Sequencing sequence VBG 10_1101-2021_01_07_425675 206 7 the the DT 10_1101-2021_01_07_425675 206 8 functional functional JJ 10_1101-2021_01_07_425675 206 9 antibody antibody NN 10_1101-2021_01_07_425675 206 10 repertoire repertoire NN 10_1101-2021_01_07_425675 206 11 — — : 10_1101-2021_01_07_425675 206 12 diagnostic diagnostic JJ 10_1101-2021_01_07_425675 206 13 and and CC 10_1101-2021_01_07_425675 206 14 371 371 CD 10_1101-2021_01_07_425675 206 15 therapeutic therapeutic JJ 10_1101-2021_01_07_425675 206 16 discovery discovery NN 10_1101-2021_01_07_425675 206 17 . . . 10_1101-2021_01_07_425675 207 1 Nature Nature NNP 10_1101-2021_01_07_425675 207 2 Reviews Reviews NNPS 10_1101-2021_01_07_425675 207 3 Rheumatology Rheumatology NNP 10_1101-2021_01_07_425675 207 4 2015 2015 CD 10_1101-2021_01_07_425675 207 5 , , , 10_1101-2021_01_07_425675 207 6 11 11 CD 10_1101-2021_01_07_425675 207 7 ( ( -LRB- 10_1101-2021_01_07_425675 207 8 3 3 CD 10_1101-2021_01_07_425675 207 9 ) ) -RRB- 10_1101-2021_01_07_425675 207 10 , , , 10_1101-2021_01_07_425675 207 11 171 171 CD 10_1101-2021_01_07_425675 207 12 . . . 10_1101-2021_01_07_425675 208 1 372 372 CD 10_1101-2021_01_07_425675 208 2 10 10 CD 10_1101-2021_01_07_425675 208 3 . . . 10_1101-2021_01_07_425675 209 1 Boutz Boutz NNP 10_1101-2021_01_07_425675 209 2 , , , 10_1101-2021_01_07_425675 209 3 D. D. NNP 10_1101-2021_01_07_425675 209 4 R. R. NNP 10_1101-2021_01_07_425675 209 5 ; ; : 10_1101-2021_01_07_425675 209 6 Horton Horton NNP 10_1101-2021_01_07_425675 209 7 , , , 10_1101-2021_01_07_425675 209 8 A. A. NNP 10_1101-2021_01_07_425675 209 9 P. P. NNP 10_1101-2021_01_07_425675 209 10 ; ; : 10_1101-2021_01_07_425675 209 11 Wine Wine NNP 10_1101-2021_01_07_425675 209 12 , , , 10_1101-2021_01_07_425675 209 13 Y. Y. NNP 10_1101-2021_01_07_425675 209 14 ; ; : 10_1101-2021_01_07_425675 209 15 Lavinder Lavinder NNP 10_1101-2021_01_07_425675 209 16 , , , 10_1101-2021_01_07_425675 209 17 J. J. NNP 10_1101-2021_01_07_425675 209 18 J. J. NNP 10_1101-2021_01_07_425675 209 19 ; ; : 10_1101-2021_01_07_425675 209 20 Georgiou Georgiou NNP 10_1101-2021_01_07_425675 209 21 , , , 10_1101-2021_01_07_425675 209 22 G. G. NNP 10_1101-2021_01_07_425675 209 23 ; ; : 10_1101-2021_01_07_425675 209 24 Marcotte Marcotte NNP 10_1101-2021_01_07_425675 209 25 , , , 10_1101-2021_01_07_425675 209 26 E. E. NNP 10_1101-2021_01_07_425675 209 27 M. M. NNP 10_1101-2021_01_07_425675 209 28 , , , 10_1101-2021_01_07_425675 209 29 373 373 CD 10_1101-2021_01_07_425675 209 30 Proteomic proteomic JJ 10_1101-2021_01_07_425675 209 31 identification identification NN 10_1101-2021_01_07_425675 209 32 of of IN 10_1101-2021_01_07_425675 209 33 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 209 34 antibodies antibody NNS 10_1101-2021_01_07_425675 209 35 from from IN 10_1101-2021_01_07_425675 209 36 serum serum NNP 10_1101-2021_01_07_425675 209 37 . . . 10_1101-2021_01_07_425675 210 1 Analytical analytical JJ 10_1101-2021_01_07_425675 210 2 chemistry chemistry NN 10_1101-2021_01_07_425675 210 3 2014 2014 CD 10_1101-2021_01_07_425675 210 4 , , , 10_1101-2021_01_07_425675 210 5 86 86 CD 10_1101-2021_01_07_425675 210 6 374 374 CD 10_1101-2021_01_07_425675 210 7 ( ( -LRB- 10_1101-2021_01_07_425675 210 8 10 10 CD 10_1101-2021_01_07_425675 210 9 ) ) -RRB- 10_1101-2021_01_07_425675 210 10 , , , 10_1101-2021_01_07_425675 210 11 4758 4758 CD 10_1101-2021_01_07_425675 210 12 - - SYM 10_1101-2021_01_07_425675 210 13 4766 4766 CD 10_1101-2021_01_07_425675 210 14 . . . 10_1101-2021_01_07_425675 211 1 375 375 CD 10_1101-2021_01_07_425675 211 2 11 11 CD 10_1101-2021_01_07_425675 211 3 . . . 10_1101-2021_01_07_425675 212 1 Castellana Castellana NNP 10_1101-2021_01_07_425675 212 2 , , , 10_1101-2021_01_07_425675 212 3 N. N. NNP 10_1101-2021_01_07_425675 212 4 E. E. NNP 10_1101-2021_01_07_425675 212 5 ; ; : 10_1101-2021_01_07_425675 212 6 McCutcheon McCutcheon NNP 10_1101-2021_01_07_425675 212 7 , , , 10_1101-2021_01_07_425675 212 8 K. K. NNP 10_1101-2021_01_07_425675 212 9 ; ; : 10_1101-2021_01_07_425675 212 10 Pham Pham NNP 10_1101-2021_01_07_425675 212 11 , , , 10_1101-2021_01_07_425675 212 12 V. V. NNP 10_1101-2021_01_07_425675 212 13 C. C. NNP 10_1101-2021_01_07_425675 212 14 ; ; : 10_1101-2021_01_07_425675 212 15 Harden Harden NNP 10_1101-2021_01_07_425675 212 16 , , , 10_1101-2021_01_07_425675 212 17 K. K. NNP 10_1101-2021_01_07_425675 212 18 ; ; : 10_1101-2021_01_07_425675 212 19 Nguyen Nguyen NNP 10_1101-2021_01_07_425675 212 20 , , , 10_1101-2021_01_07_425675 212 21 A. a. NN 10_1101-2021_01_07_425675 212 22 ; ; : 10_1101-2021_01_07_425675 212 23 Young Young NNP 10_1101-2021_01_07_425675 212 24 , , , 10_1101-2021_01_07_425675 212 25 J. J. NNP 10_1101-2021_01_07_425675 212 26 ; ; : 10_1101-2021_01_07_425675 212 27 376 376 CD 10_1101-2021_01_07_425675 212 28 Adams Adams NNP 10_1101-2021_01_07_425675 212 29 , , , 10_1101-2021_01_07_425675 212 30 C. C. NNP 10_1101-2021_01_07_425675 212 31 ; ; : 10_1101-2021_01_07_425675 212 32 Schroeder Schroeder NNP 10_1101-2021_01_07_425675 212 33 , , , 10_1101-2021_01_07_425675 212 34 K. K. NNP 10_1101-2021_01_07_425675 212 35 ; ; : 10_1101-2021_01_07_425675 212 36 Arnott Arnott NNP 10_1101-2021_01_07_425675 212 37 , , , 10_1101-2021_01_07_425675 212 38 D. D. NNP 10_1101-2021_01_07_425675 212 39 ; ; : 10_1101-2021_01_07_425675 212 40 Bafna Bafna NNP 10_1101-2021_01_07_425675 212 41 , , , 10_1101-2021_01_07_425675 212 42 V. V. NNP 10_1101-2021_01_07_425675 212 43 , , , 10_1101-2021_01_07_425675 212 44 Resurrection Resurrection NNP 10_1101-2021_01_07_425675 212 45 of of IN 10_1101-2021_01_07_425675 212 46 a a DT 10_1101-2021_01_07_425675 212 47 clinical clinical JJ 10_1101-2021_01_07_425675 212 48 antibody antibody NN 10_1101-2021_01_07_425675 212 49 : : : 10_1101-2021_01_07_425675 212 50 Template template NN 10_1101-2021_01_07_425675 212 51 377 377 CD 10_1101-2021_01_07_425675 212 52 proteogenomic proteogenomic NN 10_1101-2021_01_07_425675 212 53 de de FW 10_1101-2021_01_07_425675 212 54 novo novo NNP 10_1101-2021_01_07_425675 212 55 proteomic proteomic NNP 10_1101-2021_01_07_425675 212 56 sequencing sequencing NNP 10_1101-2021_01_07_425675 212 57 and and CC 10_1101-2021_01_07_425675 212 58 reverse reverse VB 10_1101-2021_01_07_425675 212 59 engineering engineering NN 10_1101-2021_01_07_425675 212 60 of of IN 10_1101-2021_01_07_425675 212 61 an an DT 10_1101-2021_01_07_425675 212 62 anti anti JJ 10_1101-2021_01_07_425675 212 63 - - JJ 10_1101-2021_01_07_425675 212 64 lymphotoxin-378 lymphotoxin-378 JJ 10_1101-2021_01_07_425675 212 65 α α NNP 10_1101-2021_01_07_425675 212 66 antibody antibody NN 10_1101-2021_01_07_425675 212 67 . . . 10_1101-2021_01_07_425675 213 1 Proteomics proteomic NNS 10_1101-2021_01_07_425675 213 2 2011 2011 CD 10_1101-2021_01_07_425675 213 3 , , , 10_1101-2021_01_07_425675 213 4 11 11 CD 10_1101-2021_01_07_425675 213 5 ( ( -LRB- 10_1101-2021_01_07_425675 213 6 3 3 CD 10_1101-2021_01_07_425675 213 7 ) ) -RRB- 10_1101-2021_01_07_425675 213 8 , , , 10_1101-2021_01_07_425675 213 9 395 395 CD 10_1101-2021_01_07_425675 213 10 - - SYM 10_1101-2021_01_07_425675 213 11 405 405 CD 10_1101-2021_01_07_425675 213 12 . . . 10_1101-2021_01_07_425675 214 1 379 379 CD 10_1101-2021_01_07_425675 214 2 12 12 CD 10_1101-2021_01_07_425675 214 3 . . . 10_1101-2021_01_07_425675 215 1 Chen Chen NNP 10_1101-2021_01_07_425675 215 2 , , , 10_1101-2021_01_07_425675 215 3 J. J. NNP 10_1101-2021_01_07_425675 215 4 ; ; : 10_1101-2021_01_07_425675 215 5 Zheng Zheng NNP 10_1101-2021_01_07_425675 215 6 , , , 10_1101-2021_01_07_425675 215 7 Q. Q. NNP 10_1101-2021_01_07_425675 215 8 ; ; : 10_1101-2021_01_07_425675 215 9 Hammers Hammers NNP 10_1101-2021_01_07_425675 215 10 , , , 10_1101-2021_01_07_425675 215 11 C. C. NNP 10_1101-2021_01_07_425675 215 12 M. M. NNP 10_1101-2021_01_07_425675 215 13 ; ; : 10_1101-2021_01_07_425675 215 14 Ellebrecht Ellebrecht NNP 10_1101-2021_01_07_425675 215 15 , , , 10_1101-2021_01_07_425675 215 16 C. C. NNP 10_1101-2021_01_07_425675 215 17 T. T. NNP 10_1101-2021_01_07_425675 215 18 ; ; : 10_1101-2021_01_07_425675 215 19 Mukherjee Mukherjee NNP 10_1101-2021_01_07_425675 215 20 , , , 10_1101-2021_01_07_425675 215 21 E. E. NNP 10_1101-2021_01_07_425675 215 22 M. M. NNP 10_1101-2021_01_07_425675 215 23 ; ; : 10_1101-2021_01_07_425675 215 24 Tang Tang NNP 10_1101-2021_01_07_425675 215 25 , , , 10_1101-2021_01_07_425675 215 26 H.-Y. H.-Y. NNP 10_1101-2021_01_07_425675 216 1 ; ; : 10_1101-2021_01_07_425675 216 2 380 380 CD 10_1101-2021_01_07_425675 216 3 Lin Lin NNP 10_1101-2021_01_07_425675 216 4 , , , 10_1101-2021_01_07_425675 216 5 C. C. NNP 10_1101-2021_01_07_425675 216 6 ; ; : 10_1101-2021_01_07_425675 216 7 Yuan Yuan NNP 10_1101-2021_01_07_425675 216 8 , , , 10_1101-2021_01_07_425675 216 9 H. H. NNP 10_1101-2021_01_07_425675 216 10 ; ; : 10_1101-2021_01_07_425675 216 11 Pan Pan NNP 10_1101-2021_01_07_425675 216 12 , , , 10_1101-2021_01_07_425675 216 13 M. M. NNP 10_1101-2021_01_07_425675 216 14 ; ; : 10_1101-2021_01_07_425675 216 15 Langenhan Langenhan NNP 10_1101-2021_01_07_425675 216 16 , , , 10_1101-2021_01_07_425675 216 17 J. J. NNP 10_1101-2021_01_07_425675 216 18 , , , 10_1101-2021_01_07_425675 216 19 Proteomic proteomic JJ 10_1101-2021_01_07_425675 216 20 analysis analysis NN 10_1101-2021_01_07_425675 216 21 of of IN 10_1101-2021_01_07_425675 216 22 pemphigus pemphigus JJ 10_1101-2021_01_07_425675 216 23 autoantibodies autoantibody NNS 10_1101-2021_01_07_425675 216 24 381 381 CD 10_1101-2021_01_07_425675 216 25 indicates indicate VBZ 10_1101-2021_01_07_425675 216 26 a a DT 10_1101-2021_01_07_425675 216 27 larger large JJR 10_1101-2021_01_07_425675 216 28 , , , 10_1101-2021_01_07_425675 216 29 more more RBR 10_1101-2021_01_07_425675 216 30 diverse diverse JJ 10_1101-2021_01_07_425675 216 31 , , , 10_1101-2021_01_07_425675 216 32 and and CC 10_1101-2021_01_07_425675 216 33 more more RBR 10_1101-2021_01_07_425675 216 34 dynamic dynamic JJ 10_1101-2021_01_07_425675 216 35 repertoire repertoire NN 10_1101-2021_01_07_425675 216 36 than than IN 10_1101-2021_01_07_425675 216 37 determined determine VBN 10_1101-2021_01_07_425675 216 38 by by IN 10_1101-2021_01_07_425675 216 39 B b NN 10_1101-2021_01_07_425675 216 40 cell cell NN 10_1101-2021_01_07_425675 216 41 382 382 CD 10_1101-2021_01_07_425675 216 42 genetics genetic NNS 10_1101-2021_01_07_425675 216 43 . . . 10_1101-2021_01_07_425675 217 1 Cell cell NN 10_1101-2021_01_07_425675 217 2 reports report VBZ 10_1101-2021_01_07_425675 217 3 2017 2017 CD 10_1101-2021_01_07_425675 217 4 , , , 10_1101-2021_01_07_425675 217 5 18 18 CD 10_1101-2021_01_07_425675 217 6 ( ( -LRB- 10_1101-2021_01_07_425675 217 7 1 1 CD 10_1101-2021_01_07_425675 217 8 ) ) -RRB- 10_1101-2021_01_07_425675 217 9 , , , 10_1101-2021_01_07_425675 217 10 237 237 CD 10_1101-2021_01_07_425675 217 11 - - SYM 10_1101-2021_01_07_425675 217 12 247 247 CD 10_1101-2021_01_07_425675 217 13 . . . 10_1101-2021_01_07_425675 218 1 383 383 CD 10_1101-2021_01_07_425675 218 2 13 13 CD 10_1101-2021_01_07_425675 218 3 . . . 10_1101-2021_01_07_425675 219 1 Cheung Cheung NNP 10_1101-2021_01_07_425675 219 2 , , , 10_1101-2021_01_07_425675 219 3 W. W. NNP 10_1101-2021_01_07_425675 219 4 C. C. NNP 10_1101-2021_01_07_425675 219 5 ; ; : 10_1101-2021_01_07_425675 219 6 Beausoleil Beausoleil NNP 10_1101-2021_01_07_425675 219 7 , , , 10_1101-2021_01_07_425675 219 8 S. S. NNP 10_1101-2021_01_07_425675 219 9 A. A. NNP 10_1101-2021_01_07_425675 219 10 ; ; : 10_1101-2021_01_07_425675 219 11 Zhang Zhang NNP 10_1101-2021_01_07_425675 219 12 , , , 10_1101-2021_01_07_425675 219 13 X. X. NNP 10_1101-2021_01_07_425675 219 14 ; ; : 10_1101-2021_01_07_425675 219 15 Sato Sato NNP 10_1101-2021_01_07_425675 219 16 , , , 10_1101-2021_01_07_425675 219 17 S. S. NNP 10_1101-2021_01_07_425675 219 18 ; ; : 10_1101-2021_01_07_425675 219 19 Schieferl Schieferl NNP 10_1101-2021_01_07_425675 219 20 , , , 10_1101-2021_01_07_425675 219 21 S. S. NNP 10_1101-2021_01_07_425675 219 22 M. M. NNP 10_1101-2021_01_07_425675 219 23 ; ; : 10_1101-2021_01_07_425675 219 24 Wieler Wieler NNP 10_1101-2021_01_07_425675 219 25 , , , 10_1101-2021_01_07_425675 219 26 J. J. NNP 10_1101-2021_01_07_425675 219 27 S. S. NNP 10_1101-2021_01_07_425675 219 28 ; ; : 10_1101-2021_01_07_425675 219 29 384 384 CD 10_1101-2021_01_07_425675 219 30 Beaudet Beaudet NNP 10_1101-2021_01_07_425675 219 31 , , , 10_1101-2021_01_07_425675 219 32 J. J. NNP 10_1101-2021_01_07_425675 219 33 G. G. NNP 10_1101-2021_01_07_425675 219 34 ; ; : 10_1101-2021_01_07_425675 219 35 Ramenani Ramenani NNP 10_1101-2021_01_07_425675 219 36 , , , 10_1101-2021_01_07_425675 219 37 R. R. NNP 10_1101-2021_01_07_425675 219 38 K. K. NNP 10_1101-2021_01_07_425675 219 39 ; ; : 10_1101-2021_01_07_425675 219 40 Popova Popova NNP 10_1101-2021_01_07_425675 219 41 , , , 10_1101-2021_01_07_425675 219 42 L. L. NNP 10_1101-2021_01_07_425675 219 43 ; ; : 10_1101-2021_01_07_425675 219 44 Comb Comb NNP 10_1101-2021_01_07_425675 219 45 , , , 10_1101-2021_01_07_425675 219 46 M. M. NNP 10_1101-2021_01_07_425675 219 47 J. J. NNP 10_1101-2021_01_07_425675 219 48 , , , 10_1101-2021_01_07_425675 219 49 A a DT 10_1101-2021_01_07_425675 219 50 proteomics proteomic NNS 10_1101-2021_01_07_425675 219 51 approach approach NN 10_1101-2021_01_07_425675 219 52 for for IN 10_1101-2021_01_07_425675 219 53 the the DT 10_1101-2021_01_07_425675 219 54 385 385 CD 10_1101-2021_01_07_425675 219 55 identification identification NN 10_1101-2021_01_07_425675 219 56 and and CC 10_1101-2021_01_07_425675 219 57 cloning clone VBG 10_1101-2021_01_07_425675 219 58 of of IN 10_1101-2021_01_07_425675 219 59 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 219 60 antibodies antibody NNS 10_1101-2021_01_07_425675 219 61 from from IN 10_1101-2021_01_07_425675 219 62 serum serum NNP 10_1101-2021_01_07_425675 219 63 . . . 10_1101-2021_01_07_425675 220 1 Nature nature NN 10_1101-2021_01_07_425675 220 2 biotechnology biotechnology NN 10_1101-2021_01_07_425675 220 3 2012 2012 CD 10_1101-2021_01_07_425675 220 4 , , , 10_1101-2021_01_07_425675 220 5 30 30 CD 10_1101-2021_01_07_425675 220 6 386 386 CD 10_1101-2021_01_07_425675 220 7 ( ( -LRB- 10_1101-2021_01_07_425675 220 8 5 5 CD 10_1101-2021_01_07_425675 220 9 ) ) -RRB- 10_1101-2021_01_07_425675 220 10 , , , 10_1101-2021_01_07_425675 220 11 447 447 CD 10_1101-2021_01_07_425675 220 12 - - SYM 10_1101-2021_01_07_425675 220 13 452 452 CD 10_1101-2021_01_07_425675 220 14 . . . 10_1101-2021_01_07_425675 221 1 387 387 CD 10_1101-2021_01_07_425675 221 2 14 14 CD 10_1101-2021_01_07_425675 221 3 . . . 10_1101-2021_01_07_425675 222 1 Guthals guthal NNS 10_1101-2021_01_07_425675 222 2 , , , 10_1101-2021_01_07_425675 222 3 A. a. NN 10_1101-2021_01_07_425675 222 4 ; ; : 10_1101-2021_01_07_425675 222 5 Gan Gan NNP 10_1101-2021_01_07_425675 222 6 , , , 10_1101-2021_01_07_425675 222 7 Y. Y. NNP 10_1101-2021_01_07_425675 222 8 ; ; : 10_1101-2021_01_07_425675 222 9 Murray Murray NNP 10_1101-2021_01_07_425675 222 10 , , , 10_1101-2021_01_07_425675 222 11 L. L. NNP 10_1101-2021_01_07_425675 222 12 ; ; : 10_1101-2021_01_07_425675 222 13 Chen Chen NNP 10_1101-2021_01_07_425675 222 14 , , , 10_1101-2021_01_07_425675 222 15 Y. Y. NNP 10_1101-2021_01_07_425675 222 16 ; ; : 10_1101-2021_01_07_425675 222 17 Stinson Stinson NNP 10_1101-2021_01_07_425675 222 18 , , , 10_1101-2021_01_07_425675 222 19 J. J. NNP 10_1101-2021_01_07_425675 222 20 ; ; : 10_1101-2021_01_07_425675 222 21 Nakamura Nakamura NNP 10_1101-2021_01_07_425675 222 22 , , , 10_1101-2021_01_07_425675 222 23 G. G. NNP 10_1101-2021_01_07_425675 222 24 ; ; : 10_1101-2021_01_07_425675 222 25 Lill Lill NNP 10_1101-2021_01_07_425675 222 26 , , , 10_1101-2021_01_07_425675 222 27 J. J. NNP 10_1101-2021_01_07_425675 222 28 R. R. NNP 10_1101-2021_01_07_425675 222 29 ; ; : 10_1101-2021_01_07_425675 222 30 388 388 CD 10_1101-2021_01_07_425675 222 31 Sandoval Sandoval NNP 10_1101-2021_01_07_425675 222 32 , , , 10_1101-2021_01_07_425675 222 33 W. W. NNP 10_1101-2021_01_07_425675 222 34 ; ; : 10_1101-2021_01_07_425675 222 35 Bandeira Bandeira NNP 10_1101-2021_01_07_425675 222 36 , , , 10_1101-2021_01_07_425675 222 37 N. N. NNP 10_1101-2021_01_07_425675 222 38 , , , 10_1101-2021_01_07_425675 222 39 De De NNP 10_1101-2021_01_07_425675 222 40 novo novo NNP 10_1101-2021_01_07_425675 222 41 MS MS NNP 10_1101-2021_01_07_425675 222 42 / / SYM 10_1101-2021_01_07_425675 222 43 MS MS NNP 10_1101-2021_01_07_425675 222 44 sequencing sequencing NN 10_1101-2021_01_07_425675 222 45 of of IN 10_1101-2021_01_07_425675 222 46 native native JJ 10_1101-2021_01_07_425675 222 47 human human JJ 10_1101-2021_01_07_425675 222 48 antibodies antibody NNS 10_1101-2021_01_07_425675 222 49 . . . 10_1101-2021_01_07_425675 223 1 Journal Journal NNP 10_1101-2021_01_07_425675 223 2 of of IN 10_1101-2021_01_07_425675 223 3 389 389 CD 10_1101-2021_01_07_425675 223 4 proteome proteome NN 10_1101-2021_01_07_425675 223 5 research research NN 10_1101-2021_01_07_425675 223 6 2017 2017 CD 10_1101-2021_01_07_425675 223 7 , , , 10_1101-2021_01_07_425675 223 8 16 16 CD 10_1101-2021_01_07_425675 223 9 ( ( -LRB- 10_1101-2021_01_07_425675 223 10 1 1 CD 10_1101-2021_01_07_425675 223 11 ) ) -RRB- 10_1101-2021_01_07_425675 223 12 , , , 10_1101-2021_01_07_425675 223 13 45 45 CD 10_1101-2021_01_07_425675 223 14 - - SYM 10_1101-2021_01_07_425675 223 15 54 54 CD 10_1101-2021_01_07_425675 223 16 . . . 10_1101-2021_01_07_425675 224 1 390 390 CD 10_1101-2021_01_07_425675 224 2 15 15 CD 10_1101-2021_01_07_425675 224 3 . . . 10_1101-2021_01_07_425675 225 1 Lee Lee NNP 10_1101-2021_01_07_425675 225 2 , , , 10_1101-2021_01_07_425675 225 3 J. J. NNP 10_1101-2021_01_07_425675 225 4 ; ; : 10_1101-2021_01_07_425675 225 5 Boutz Boutz NNP 10_1101-2021_01_07_425675 225 6 , , , 10_1101-2021_01_07_425675 225 7 D. D. NNP 10_1101-2021_01_07_425675 225 8 R. R. NNP 10_1101-2021_01_07_425675 225 9 ; ; : 10_1101-2021_01_07_425675 225 10 Chromikova Chromikova NNP 10_1101-2021_01_07_425675 225 11 , , , 10_1101-2021_01_07_425675 225 12 V. V. NNP 10_1101-2021_01_07_425675 225 13 ; ; : 10_1101-2021_01_07_425675 225 14 Joyce Joyce NNP 10_1101-2021_01_07_425675 225 15 , , , 10_1101-2021_01_07_425675 225 16 M. M. NNP 10_1101-2021_01_07_425675 225 17 G. G. NNP 10_1101-2021_01_07_425675 225 18 ; ; : 10_1101-2021_01_07_425675 225 19 Vollmers Vollmers NNP 10_1101-2021_01_07_425675 225 20 , , , 10_1101-2021_01_07_425675 225 21 C. C. NNP 10_1101-2021_01_07_425675 225 22 ; ; : 10_1101-2021_01_07_425675 225 23 Leung Leung NNP 10_1101-2021_01_07_425675 225 24 , , , 10_1101-2021_01_07_425675 225 25 K. K. NNP 10_1101-2021_01_07_425675 225 26 ; ; : 10_1101-2021_01_07_425675 225 27 Horton Horton NNP 10_1101-2021_01_07_425675 225 28 , , , 10_1101-2021_01_07_425675 225 29 A. a. NN 10_1101-2021_01_07_425675 226 1 391 391 CD 10_1101-2021_01_07_425675 226 2 P. P. NNP 10_1101-2021_01_07_425675 226 3 ; ; : 10_1101-2021_01_07_425675 226 4 DeKosky DeKosky NNP 10_1101-2021_01_07_425675 226 5 , , , 10_1101-2021_01_07_425675 226 6 B. B. NNP 10_1101-2021_01_07_425675 226 7 J. J. NNP 10_1101-2021_01_07_425675 226 8 ; ; : 10_1101-2021_01_07_425675 226 9 Lee Lee NNP 10_1101-2021_01_07_425675 226 10 , , , 10_1101-2021_01_07_425675 226 11 C.-H. C.-H. NNP 10_1101-2021_01_07_425675 226 12 ; ; : 10_1101-2021_01_07_425675 226 13 Lavinder Lavinder NNP 10_1101-2021_01_07_425675 226 14 , , , 10_1101-2021_01_07_425675 226 15 J. J. NNP 10_1101-2021_01_07_425675 226 16 J. J. NNP 10_1101-2021_01_07_425675 226 17 , , , 10_1101-2021_01_07_425675 226 18 Molecular Molecular NNP 10_1101-2021_01_07_425675 226 19 - - HYPH 10_1101-2021_01_07_425675 226 20 level level NN 10_1101-2021_01_07_425675 226 21 analysis analysis NN 10_1101-2021_01_07_425675 226 22 of of IN 10_1101-2021_01_07_425675 226 23 the the DT 10_1101-2021_01_07_425675 226 24 serum serum NNP 10_1101-2021_01_07_425675 226 25 antibody antibody NN 10_1101-2021_01_07_425675 226 26 392 392 CD 10_1101-2021_01_07_425675 226 27 repertoire repertoire NN 10_1101-2021_01_07_425675 226 28 in in IN 10_1101-2021_01_07_425675 226 29 young young JJ 10_1101-2021_01_07_425675 226 30 adults adult NNS 10_1101-2021_01_07_425675 226 31 before before IN 10_1101-2021_01_07_425675 226 32 and and CC 10_1101-2021_01_07_425675 226 33 after after IN 10_1101-2021_01_07_425675 226 34 seasonal seasonal JJ 10_1101-2021_01_07_425675 226 35 influenza influenza NN 10_1101-2021_01_07_425675 226 36 vaccination vaccination NN 10_1101-2021_01_07_425675 226 37 . . . 10_1101-2021_01_07_425675 227 1 Nature nature NN 10_1101-2021_01_07_425675 227 2 medicine medicine NN 10_1101-2021_01_07_425675 227 3 393 393 CD 10_1101-2021_01_07_425675 227 4 2016 2016 CD 10_1101-2021_01_07_425675 227 5 , , , 10_1101-2021_01_07_425675 227 6 22 22 CD 10_1101-2021_01_07_425675 227 7 ( ( -LRB- 10_1101-2021_01_07_425675 227 8 12 12 CD 10_1101-2021_01_07_425675 227 9 ) ) -RRB- 10_1101-2021_01_07_425675 227 10 , , , 10_1101-2021_01_07_425675 227 11 1456 1456 CD 10_1101-2021_01_07_425675 227 12 - - SYM 10_1101-2021_01_07_425675 227 13 1464 1464 CD 10_1101-2021_01_07_425675 227 14 . . . 10_1101-2021_01_07_425675 228 1 394 394 CD 10_1101-2021_01_07_425675 228 2 16 16 CD 10_1101-2021_01_07_425675 228 3 . . . 10_1101-2021_01_07_425675 229 1 Lee Lee NNP 10_1101-2021_01_07_425675 229 2 , , , 10_1101-2021_01_07_425675 229 3 J. J. NNP 10_1101-2021_01_07_425675 229 4 ; ; : 10_1101-2021_01_07_425675 229 5 Paparoditis Paparoditis NNP 10_1101-2021_01_07_425675 229 6 , , , 10_1101-2021_01_07_425675 229 7 P. P. NNP 10_1101-2021_01_07_425675 229 8 ; ; : 10_1101-2021_01_07_425675 229 9 Horton Horton NNP 10_1101-2021_01_07_425675 229 10 , , , 10_1101-2021_01_07_425675 229 11 A. A. NNP 10_1101-2021_01_07_425675 229 12 P. P. NNP 10_1101-2021_01_07_425675 229 13 ; ; : 10_1101-2021_01_07_425675 229 14 Frühwirth Frühwirth NNP 10_1101-2021_01_07_425675 229 15 , , , 10_1101-2021_01_07_425675 229 16 A. A. NNP 10_1101-2021_01_07_425675 229 17 ; ; : 10_1101-2021_01_07_425675 229 18 McDaniel McDaniel NNP 10_1101-2021_01_07_425675 229 19 , , , 10_1101-2021_01_07_425675 229 20 J. J. NNP 10_1101-2021_01_07_425675 229 21 R. R. NNP 10_1101-2021_01_07_425675 229 22 ; ; : 10_1101-2021_01_07_425675 229 23 Jung Jung NNP 10_1101-2021_01_07_425675 229 24 , , , 10_1101-2021_01_07_425675 229 25 J. J. NNP 10_1101-2021_01_07_425675 229 26 ; ; : 10_1101-2021_01_07_425675 229 27 Boutz Boutz NNP 10_1101-2021_01_07_425675 229 28 , , , 10_1101-2021_01_07_425675 229 29 D. D. NNP 10_1101-2021_01_07_425675 229 30 395 395 CD 10_1101-2021_01_07_425675 229 31 R. R. NNP 10_1101-2021_01_07_425675 229 32 ; ; : 10_1101-2021_01_07_425675 229 33 Hussein Hussein NNP 10_1101-2021_01_07_425675 229 34 , , , 10_1101-2021_01_07_425675 229 35 D. D. NNP 10_1101-2021_01_07_425675 229 36 A. A. NNP 10_1101-2021_01_07_425675 229 37 ; ; : 10_1101-2021_01_07_425675 229 38 Tanno Tanno NNP 10_1101-2021_01_07_425675 229 39 , , , 10_1101-2021_01_07_425675 229 40 Y. Y. NNP 10_1101-2021_01_07_425675 229 41 ; ; : 10_1101-2021_01_07_425675 229 42 Pappas Pappas NNP 10_1101-2021_01_07_425675 229 43 , , , 10_1101-2021_01_07_425675 229 44 L. L. NNP 10_1101-2021_01_07_425675 229 45 , , , 10_1101-2021_01_07_425675 229 46 Persistent persistent JJ 10_1101-2021_01_07_425675 229 47 antibody antibody NN 10_1101-2021_01_07_425675 229 48 clonotypes clonotype NNS 10_1101-2021_01_07_425675 229 49 dominate dominate VBP 10_1101-2021_01_07_425675 229 50 the the DT 10_1101-2021_01_07_425675 229 51 serum serum NN 10_1101-2021_01_07_425675 229 52 396 396 CD 10_1101-2021_01_07_425675 229 53 response response NN 10_1101-2021_01_07_425675 229 54 to to TO 10_1101-2021_01_07_425675 229 55 influenza influenza VB 10_1101-2021_01_07_425675 229 56 over over IN 10_1101-2021_01_07_425675 229 57 multiple multiple JJ 10_1101-2021_01_07_425675 229 58 years year NNS 10_1101-2021_01_07_425675 229 59 and and CC 10_1101-2021_01_07_425675 229 60 repeated repeat VBN 10_1101-2021_01_07_425675 229 61 vaccinations vaccination NNS 10_1101-2021_01_07_425675 229 62 . . . 10_1101-2021_01_07_425675 230 1 Cell Cell NNP 10_1101-2021_01_07_425675 230 2 host host NN 10_1101-2021_01_07_425675 230 3 & & CC 10_1101-2021_01_07_425675 230 4 microbe microbe NNP 10_1101-2021_01_07_425675 230 5 2019 2019 CD 10_1101-2021_01_07_425675 230 6 , , , 10_1101-2021_01_07_425675 230 7 397 397 CD 10_1101-2021_01_07_425675 230 8 25 25 CD 10_1101-2021_01_07_425675 230 9 ( ( -LRB- 10_1101-2021_01_07_425675 230 10 3 3 CD 10_1101-2021_01_07_425675 230 11 ) ) -RRB- 10_1101-2021_01_07_425675 230 12 , , , 10_1101-2021_01_07_425675 230 13 367 367 CD 10_1101-2021_01_07_425675 230 14 - - SYM 10_1101-2021_01_07_425675 230 15 376 376 CD 10_1101-2021_01_07_425675 230 16 . . . 10_1101-2021_01_07_425675 230 17 e5 e5 NN 10_1101-2021_01_07_425675 230 18 . . . 10_1101-2021_01_07_425675 231 1 398 398 CD 10_1101-2021_01_07_425675 231 2 17 17 CD 10_1101-2021_01_07_425675 231 3 . . . 10_1101-2021_01_07_425675 232 1 Lindesmith Lindesmith NNP 10_1101-2021_01_07_425675 232 2 , , , 10_1101-2021_01_07_425675 232 3 L. L. NNP 10_1101-2021_01_07_425675 232 4 C. C. NNP 10_1101-2021_01_07_425675 232 5 ; ; : 10_1101-2021_01_07_425675 232 6 McDaniel McDaniel NNP 10_1101-2021_01_07_425675 232 7 , , , 10_1101-2021_01_07_425675 232 8 J. J. NNP 10_1101-2021_01_07_425675 232 9 R. R. NNP 10_1101-2021_01_07_425675 232 10 ; ; : 10_1101-2021_01_07_425675 232 11 Changela Changela NNP 10_1101-2021_01_07_425675 232 12 , , , 10_1101-2021_01_07_425675 232 13 A. A. NNP 10_1101-2021_01_07_425675 232 14 ; ; : 10_1101-2021_01_07_425675 232 15 Verardi Verardi NNP 10_1101-2021_01_07_425675 232 16 , , , 10_1101-2021_01_07_425675 232 17 R. R. NNP 10_1101-2021_01_07_425675 232 18 ; ; : 10_1101-2021_01_07_425675 232 19 Kerr Kerr NNP 10_1101-2021_01_07_425675 232 20 , , , 10_1101-2021_01_07_425675 232 21 S. S. NNP 10_1101-2021_01_07_425675 232 22 A. A. NNP 10_1101-2021_01_07_425675 232 23 ; ; : 10_1101-2021_01_07_425675 232 24 Costantini Costantini NNP 10_1101-2021_01_07_425675 232 25 , , , 10_1101-2021_01_07_425675 232 26 V. V. NNP 10_1101-2021_01_07_425675 232 27 ; ; : 10_1101-2021_01_07_425675 232 28 399 399 CD 10_1101-2021_01_07_425675 232 29 Brewer Brewer NNP 10_1101-2021_01_07_425675 232 30 - - HYPH 10_1101-2021_01_07_425675 232 31 Jensen Jensen NNP 10_1101-2021_01_07_425675 232 32 , , , 10_1101-2021_01_07_425675 232 33 P. P. NNP 10_1101-2021_01_07_425675 232 34 D. D. NNP 10_1101-2021_01_07_425675 232 35 ; ; : 10_1101-2021_01_07_425675 232 36 Mallory Mallory NNP 10_1101-2021_01_07_425675 232 37 , , , 10_1101-2021_01_07_425675 232 38 M. M. NNP 10_1101-2021_01_07_425675 232 39 L. L. NNP 10_1101-2021_01_07_425675 232 40 ; ; : 10_1101-2021_01_07_425675 232 41 Voss Voss NNP 10_1101-2021_01_07_425675 232 42 , , , 10_1101-2021_01_07_425675 232 43 W. W. NNP 10_1101-2021_01_07_425675 232 44 N. N. NNP 10_1101-2021_01_07_425675 232 45 ; ; : 10_1101-2021_01_07_425675 232 46 Boutz Boutz NNP 10_1101-2021_01_07_425675 232 47 , , , 10_1101-2021_01_07_425675 232 48 D. D. NNP 10_1101-2021_01_07_425675 232 49 R. R. NNP 10_1101-2021_01_07_425675 232 50 , , , 10_1101-2021_01_07_425675 232 51 Sera Sera NNP 10_1101-2021_01_07_425675 232 52 antibody antibody NN 10_1101-2021_01_07_425675 232 53 repertoire repertoire NN 10_1101-2021_01_07_425675 232 54 400 400 CD 10_1101-2021_01_07_425675 232 55 analyses analysis NNS 10_1101-2021_01_07_425675 232 56 reveal reveal VB 10_1101-2021_01_07_425675 232 57 mechanisms mechanism NNS 10_1101-2021_01_07_425675 232 58 of of IN 10_1101-2021_01_07_425675 232 59 broad broad JJ 10_1101-2021_01_07_425675 232 60 and and CC 10_1101-2021_01_07_425675 232 61 pandemic pandemic JJ 10_1101-2021_01_07_425675 232 62 strain strain NN 10_1101-2021_01_07_425675 232 63 neutralizing neutralize VBG 10_1101-2021_01_07_425675 232 64 responses response NNS 10_1101-2021_01_07_425675 232 65 after after IN 10_1101-2021_01_07_425675 232 66 human human JJ 10_1101-2021_01_07_425675 232 67 401 401 CD 10_1101-2021_01_07_425675 232 68 norovirus norovirus NNP 10_1101-2021_01_07_425675 232 69 vaccination vaccination NN 10_1101-2021_01_07_425675 232 70 . . . 10_1101-2021_01_07_425675 233 1 Immunity immunity NN 10_1101-2021_01_07_425675 233 2 2019 2019 CD 10_1101-2021_01_07_425675 233 3 , , , 10_1101-2021_01_07_425675 233 4 50 50 CD 10_1101-2021_01_07_425675 233 5 ( ( -LRB- 10_1101-2021_01_07_425675 233 6 6 6 CD 10_1101-2021_01_07_425675 233 7 ) ) -RRB- 10_1101-2021_01_07_425675 233 8 , , , 10_1101-2021_01_07_425675 233 9 1530 1530 CD 10_1101-2021_01_07_425675 233 10 - - SYM 10_1101-2021_01_07_425675 233 11 1541 1541 CD 10_1101-2021_01_07_425675 233 12 . . . 10_1101-2021_01_07_425675 233 13 e8 e8 NNS 10_1101-2021_01_07_425675 233 14 . . . 10_1101-2021_01_07_425675 234 1 402 402 CD 10_1101-2021_01_07_425675 234 2 18 18 CD 10_1101-2021_01_07_425675 234 3 . . . 10_1101-2021_01_07_425675 235 1 Bandeira Bandeira NNP 10_1101-2021_01_07_425675 235 2 , , , 10_1101-2021_01_07_425675 235 3 N. N. NNP 10_1101-2021_01_07_425675 235 4 ; ; : 10_1101-2021_01_07_425675 235 5 Pham Pham NNP 10_1101-2021_01_07_425675 235 6 , , , 10_1101-2021_01_07_425675 235 7 V. V. NNP 10_1101-2021_01_07_425675 235 8 ; ; : 10_1101-2021_01_07_425675 235 9 Pevzner Pevzner NNP 10_1101-2021_01_07_425675 235 10 , , , 10_1101-2021_01_07_425675 235 11 P. P. NNP 10_1101-2021_01_07_425675 235 12 ; ; : 10_1101-2021_01_07_425675 235 13 Arnott Arnott NNP 10_1101-2021_01_07_425675 235 14 , , , 10_1101-2021_01_07_425675 235 15 D. D. NNP 10_1101-2021_01_07_425675 235 16 ; ; : 10_1101-2021_01_07_425675 235 17 Lill Lill NNP 10_1101-2021_01_07_425675 235 18 , , , 10_1101-2021_01_07_425675 235 19 J. J. NNP 10_1101-2021_01_07_425675 235 20 R. R. NNP 10_1101-2021_01_07_425675 235 21 , , , 10_1101-2021_01_07_425675 235 22 Automated Automated NNP 10_1101-2021_01_07_425675 235 23 de de NNP 10_1101-2021_01_07_425675 235 24 novo novo NNP 10_1101-2021_01_07_425675 235 25 protein protein NN 10_1101-2021_01_07_425675 235 26 403 403 CD 10_1101-2021_01_07_425675 235 27 sequencing sequencing NN 10_1101-2021_01_07_425675 235 28 of of IN 10_1101-2021_01_07_425675 235 29 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 235 30 antibodies antibody NNS 10_1101-2021_01_07_425675 235 31 . . . 10_1101-2021_01_07_425675 236 1 Nature nature NN 10_1101-2021_01_07_425675 236 2 biotechnology biotechnology NN 10_1101-2021_01_07_425675 236 3 2008 2008 CD 10_1101-2021_01_07_425675 236 4 , , , 10_1101-2021_01_07_425675 236 5 26 26 CD 10_1101-2021_01_07_425675 236 6 ( ( -LRB- 10_1101-2021_01_07_425675 236 7 12 12 CD 10_1101-2021_01_07_425675 236 8 ) ) -RRB- 10_1101-2021_01_07_425675 236 9 , , , 10_1101-2021_01_07_425675 236 10 1336 1336 CD 10_1101-2021_01_07_425675 236 11 - - SYM 10_1101-2021_01_07_425675 236 12 1338 1338 CD 10_1101-2021_01_07_425675 236 13 . . . 10_1101-2021_01_07_425675 237 1 404 404 CD 10_1101-2021_01_07_425675 237 2 19 19 CD 10_1101-2021_01_07_425675 237 3 . . . 10_1101-2021_01_07_425675 238 1 Rickert Rickert NNP 10_1101-2021_01_07_425675 238 2 , , , 10_1101-2021_01_07_425675 238 3 K. K. NNP 10_1101-2021_01_07_425675 238 4 W. W. NNP 10_1101-2021_01_07_425675 238 5 ; ; : 10_1101-2021_01_07_425675 238 6 Grinberg Grinberg NNP 10_1101-2021_01_07_425675 238 7 , , , 10_1101-2021_01_07_425675 238 8 L. L. NNP 10_1101-2021_01_07_425675 238 9 ; ; : 10_1101-2021_01_07_425675 238 10 Woods Woods NNP 10_1101-2021_01_07_425675 238 11 , , , 10_1101-2021_01_07_425675 238 12 R. R. NNP 10_1101-2021_01_07_425675 238 13 M. M. NNP 10_1101-2021_01_07_425675 238 14 ; ; : 10_1101-2021_01_07_425675 238 15 Wilson Wilson NNP 10_1101-2021_01_07_425675 238 16 , , , 10_1101-2021_01_07_425675 238 17 S. S. NNP 10_1101-2021_01_07_425675 238 18 ; ; : 10_1101-2021_01_07_425675 238 19 Bowen Bowen NNP 10_1101-2021_01_07_425675 238 20 , , , 10_1101-2021_01_07_425675 238 21 M. M. NNP 10_1101-2021_01_07_425675 238 22 A. A. NNP 10_1101-2021_01_07_425675 238 23 ; ; : 10_1101-2021_01_07_425675 238 24 Baca Baca NNP 10_1101-2021_01_07_425675 238 25 , , , 10_1101-2021_01_07_425675 238 26 M. M. NNP 10_1101-2021_01_07_425675 238 27 In In NNP 10_1101-2021_01_07_425675 238 28 405 405 CD 10_1101-2021_01_07_425675 238 29 Combining combine VBG 10_1101-2021_01_07_425675 238 30 phage phage NN 10_1101-2021_01_07_425675 238 31 display display NN 10_1101-2021_01_07_425675 238 32 with with IN 10_1101-2021_01_07_425675 238 33 de de FW 10_1101-2021_01_07_425675 238 34 novo novo NNP 10_1101-2021_01_07_425675 238 35 protein protein NN 10_1101-2021_01_07_425675 238 36 sequencing sequence VBG 10_1101-2021_01_07_425675 238 37 for for IN 10_1101-2021_01_07_425675 238 38 reverse reverse JJ 10_1101-2021_01_07_425675 238 39 engineering engineering NN 10_1101-2021_01_07_425675 238 40 of of IN 10_1101-2021_01_07_425675 238 41 406 406 CD 10_1101-2021_01_07_425675 238 42 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 238 43 antibodies antibody NNS 10_1101-2021_01_07_425675 238 44 , , , 10_1101-2021_01_07_425675 238 45 MAbs MAbs NNP 10_1101-2021_01_07_425675 238 46 , , , 10_1101-2021_01_07_425675 238 47 Taylor Taylor NNP 10_1101-2021_01_07_425675 238 48 & & CC 10_1101-2021_01_07_425675 238 49 Francis Francis NNP 10_1101-2021_01_07_425675 238 50 : : : 10_1101-2021_01_07_425675 238 51 2016 2016 CD 10_1101-2021_01_07_425675 238 52 ; ; : 10_1101-2021_01_07_425675 238 53 pp pp NNP 10_1101-2021_01_07_425675 238 54 501 501 CD 10_1101-2021_01_07_425675 238 55 - - SYM 10_1101-2021_01_07_425675 238 56 512 512 CD 10_1101-2021_01_07_425675 238 57 . . . 10_1101-2021_01_07_425675 239 1 407 407 CD 10_1101-2021_01_07_425675 239 2 20 20 CD 10_1101-2021_01_07_425675 239 3 . . . 10_1101-2021_01_07_425675 240 1 Savidor savidor NN 10_1101-2021_01_07_425675 240 2 , , , 10_1101-2021_01_07_425675 240 3 A. a. NN 10_1101-2021_01_07_425675 240 4 ; ; : 10_1101-2021_01_07_425675 240 5 Barzilay Barzilay NNP 10_1101-2021_01_07_425675 240 6 , , , 10_1101-2021_01_07_425675 240 7 R. R. NNP 10_1101-2021_01_07_425675 240 8 ; ; : 10_1101-2021_01_07_425675 240 9 Elinger Elinger NNP 10_1101-2021_01_07_425675 240 10 , , , 10_1101-2021_01_07_425675 240 11 D. D. NNP 10_1101-2021_01_07_425675 240 12 ; ; : 10_1101-2021_01_07_425675 240 13 Yarden Yarden NNP 10_1101-2021_01_07_425675 240 14 , , , 10_1101-2021_01_07_425675 240 15 Y. Y. NNP 10_1101-2021_01_07_425675 240 16 ; ; : 10_1101-2021_01_07_425675 240 17 Lindzen Lindzen NNP 10_1101-2021_01_07_425675 240 18 , , , 10_1101-2021_01_07_425675 240 19 M. M. NNP 10_1101-2021_01_07_425675 240 20 ; ; : 10_1101-2021_01_07_425675 240 21 Gabashvili Gabashvili NNP 10_1101-2021_01_07_425675 240 22 , , , 10_1101-2021_01_07_425675 240 23 A. a. NN 10_1101-2021_01_07_425675 240 24 ; ; : 10_1101-2021_01_07_425675 240 25 Tal Tal NNP 10_1101-2021_01_07_425675 240 26 , , , 10_1101-2021_01_07_425675 240 27 O. O. NNP 10_1101-2021_01_07_425675 241 1 A. A. NNP 10_1101-2021_01_07_425675 241 2 ; ; : 10_1101-2021_01_07_425675 241 3 408 408 CD 10_1101-2021_01_07_425675 241 4 Levin Levin NNP 10_1101-2021_01_07_425675 241 5 , , , 10_1101-2021_01_07_425675 241 6 Y. Y. NNP 10_1101-2021_01_07_425675 241 7 , , , 10_1101-2021_01_07_425675 241 8 Database Database NNP 10_1101-2021_01_07_425675 241 9 - - HYPH 10_1101-2021_01_07_425675 241 10 Independent Independent NNP 10_1101-2021_01_07_425675 241 11 Protein Protein NNP 10_1101-2021_01_07_425675 241 12 Sequencing Sequencing NNP 10_1101-2021_01_07_425675 241 13 ( ( -LRB- 10_1101-2021_01_07_425675 241 14 DiPS dips NN 10_1101-2021_01_07_425675 241 15 ) ) -RRB- 10_1101-2021_01_07_425675 241 16 Enables enable VBZ 10_1101-2021_01_07_425675 241 17 Full full JJ 10_1101-2021_01_07_425675 241 18 - - HYPH 10_1101-2021_01_07_425675 241 19 Length length NN 10_1101-2021_01_07_425675 241 20 de de IN 10_1101-2021_01_07_425675 241 21 Novo Novo NNP 10_1101-2021_01_07_425675 241 22 409 409 CD 10_1101-2021_01_07_425675 241 23 Protein Protein NNP 10_1101-2021_01_07_425675 241 24 and and CC 10_1101-2021_01_07_425675 241 25 Antibody Antibody NNP 10_1101-2021_01_07_425675 241 26 Sequence Sequence NNP 10_1101-2021_01_07_425675 241 27 Determination Determination NNP 10_1101-2021_01_07_425675 241 28 . . . 10_1101-2021_01_07_425675 242 1 Molecular Molecular NNP 10_1101-2021_01_07_425675 242 2 & & CC 10_1101-2021_01_07_425675 242 3 Cellular Cellular NNP 10_1101-2021_01_07_425675 242 4 Proteomics Proteomics NNP 10_1101-2021_01_07_425675 242 5 2017 2017 CD 10_1101-2021_01_07_425675 242 6 , , , 10_1101-2021_01_07_425675 242 7 16 16 CD 10_1101-2021_01_07_425675 242 8 ( ( -LRB- 10_1101-2021_01_07_425675 242 9 6 6 CD 10_1101-2021_01_07_425675 242 10 ) ) -RRB- 10_1101-2021_01_07_425675 242 11 , , , 10_1101-2021_01_07_425675 242 12 410 410 CD 10_1101-2021_01_07_425675 242 13 1151 1151 CD 10_1101-2021_01_07_425675 242 14 - - SYM 10_1101-2021_01_07_425675 242 15 1161 1161 CD 10_1101-2021_01_07_425675 242 16 . . . 10_1101-2021_01_07_425675 243 1 411 411 CD 10_1101-2021_01_07_425675 243 2 .CC .CC : 10_1101-2021_01_07_425675 243 3 - - : 10_1101-2021_01_07_425675 243 4 BY by IN 10_1101-2021_01_07_425675 243 5 4.0 4.0 CD 10_1101-2021_01_07_425675 243 6 International International NNP 10_1101-2021_01_07_425675 243 7 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 243 8 under under IN 10_1101-2021_01_07_425675 243 9 a a DT 10_1101-2021_01_07_425675 243 10 ( ( -LRB- 10_1101-2021_01_07_425675 243 11 which which WDT 10_1101-2021_01_07_425675 243 12 was be VBD 10_1101-2021_01_07_425675 243 13 not not RB 10_1101-2021_01_07_425675 243 14 certified certify VBN 10_1101-2021_01_07_425675 243 15 by by IN 10_1101-2021_01_07_425675 243 16 peer peer NN 10_1101-2021_01_07_425675 243 17 review review NN 10_1101-2021_01_07_425675 243 18 ) ) -RRB- 10_1101-2021_01_07_425675 243 19 is be VBZ 10_1101-2021_01_07_425675 243 20 the the DT 10_1101-2021_01_07_425675 243 21 author author NN 10_1101-2021_01_07_425675 243 22 / / SYM 10_1101-2021_01_07_425675 243 23 funder funder NN 10_1101-2021_01_07_425675 243 24 , , , 10_1101-2021_01_07_425675 243 25 who who WP 10_1101-2021_01_07_425675 243 26 has have VBZ 10_1101-2021_01_07_425675 243 27 granted grant VBN 10_1101-2021_01_07_425675 243 28 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 243 29 a a DT 10_1101-2021_01_07_425675 243 30 license license NN 10_1101-2021_01_07_425675 243 31 to to TO 10_1101-2021_01_07_425675 243 32 display display VB 10_1101-2021_01_07_425675 243 33 the the DT 10_1101-2021_01_07_425675 243 34 preprint preprint NN 10_1101-2021_01_07_425675 243 35 in in IN 10_1101-2021_01_07_425675 243 36 perpetuity perpetuity NN 10_1101-2021_01_07_425675 243 37 . . . 10_1101-2021_01_07_425675 244 1 It -PRON- PRP 10_1101-2021_01_07_425675 244 2 is be VBZ 10_1101-2021_01_07_425675 244 3 made make VBN 10_1101-2021_01_07_425675 244 4 The the DT 10_1101-2021_01_07_425675 244 5 copyright copyright NN 10_1101-2021_01_07_425675 244 6 holder holder NN 10_1101-2021_01_07_425675 244 7 for for IN 10_1101-2021_01_07_425675 244 8 this this DT 10_1101-2021_01_07_425675 244 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 244 10 version version NN 10_1101-2021_01_07_425675 244 11 posted post VBD 10_1101-2021_01_07_425675 244 12 January January NNP 10_1101-2021_01_07_425675 244 13 8 8 CD 10_1101-2021_01_07_425675 244 14 , , , 10_1101-2021_01_07_425675 244 15 2021 2021 CD 10_1101-2021_01_07_425675 244 16 . . . 10_1101-2021_01_07_425675 244 17 ; ; : 10_1101-2021_01_07_425675 244 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 244 19 : : : 10_1101-2021_01_07_425675 244 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 244 21 preprint preprint NN 10_1101-2021_01_07_425675 244 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 244 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ NNP 10_1101-2021_01_07_425675 244 24 16 16 CD 10_1101-2021_01_07_425675 244 25 21 21 CD 10_1101-2021_01_07_425675 244 26 . . . 10_1101-2021_01_07_425675 245 1 Sen Sen NNP 10_1101-2021_01_07_425675 245 2 , , , 10_1101-2021_01_07_425675 245 3 K. K. NNP 10_1101-2021_01_07_425675 245 4 I. I. NNP 10_1101-2021_01_07_425675 245 5 ; ; : 10_1101-2021_01_07_425675 245 6 Tang Tang NNP 10_1101-2021_01_07_425675 245 7 , , , 10_1101-2021_01_07_425675 245 8 W. W. NNP 10_1101-2021_01_07_425675 245 9 H. H. NNP 10_1101-2021_01_07_425675 245 10 ; ; : 10_1101-2021_01_07_425675 245 11 Nayak Nayak NNP 10_1101-2021_01_07_425675 245 12 , , , 10_1101-2021_01_07_425675 245 13 S. S. NNP 10_1101-2021_01_07_425675 245 14 ; ; : 10_1101-2021_01_07_425675 245 15 Kil Kil NNP 10_1101-2021_01_07_425675 245 16 , , , 10_1101-2021_01_07_425675 245 17 Y. Y. NNP 10_1101-2021_01_07_425675 245 18 J. J. NNP 10_1101-2021_01_07_425675 245 19 ; ; : 10_1101-2021_01_07_425675 245 20 Bern Bern NNP 10_1101-2021_01_07_425675 245 21 , , , 10_1101-2021_01_07_425675 245 22 M. M. NNP 10_1101-2021_01_07_425675 245 23 ; ; : 10_1101-2021_01_07_425675 245 24 Ozoglu Ozoglu NNP 10_1101-2021_01_07_425675 245 25 , , , 10_1101-2021_01_07_425675 245 26 B. B. NNP 10_1101-2021_01_07_425675 245 27 ; ; : 10_1101-2021_01_07_425675 245 28 Ueberheide Ueberheide NNP 10_1101-2021_01_07_425675 245 29 , , , 10_1101-2021_01_07_425675 245 30 B. B. NNP 10_1101-2021_01_07_425675 245 31 ; ; : 10_1101-2021_01_07_425675 245 32 Davis Davis NNP 10_1101-2021_01_07_425675 245 33 , , , 10_1101-2021_01_07_425675 245 34 412 412 CD 10_1101-2021_01_07_425675 245 35 D. D. NNP 10_1101-2021_01_07_425675 245 36 ; ; : 10_1101-2021_01_07_425675 245 37 Becker Becker NNP 10_1101-2021_01_07_425675 245 38 , , , 10_1101-2021_01_07_425675 245 39 C. C. NNP 10_1101-2021_01_07_425675 245 40 , , , 10_1101-2021_01_07_425675 245 41 Automated Automated NNP 10_1101-2021_01_07_425675 245 42 antibody antibody NN 10_1101-2021_01_07_425675 245 43 de de NNP 10_1101-2021_01_07_425675 245 44 novo novo NNP 10_1101-2021_01_07_425675 245 45 sequencing sequencing NNP 10_1101-2021_01_07_425675 245 46 and and CC 10_1101-2021_01_07_425675 245 47 its -PRON- PRP$ 10_1101-2021_01_07_425675 245 48 utility utility NN 10_1101-2021_01_07_425675 245 49 in in IN 10_1101-2021_01_07_425675 245 50 biopharmaceutical biopharmaceutical JJ 10_1101-2021_01_07_425675 245 51 413 413 CD 10_1101-2021_01_07_425675 245 52 discovery discovery NN 10_1101-2021_01_07_425675 245 53 . . . 10_1101-2021_01_07_425675 246 1 Journal Journal NNP 10_1101-2021_01_07_425675 246 2 of of IN 10_1101-2021_01_07_425675 246 3 The the DT 10_1101-2021_01_07_425675 246 4 American American NNP 10_1101-2021_01_07_425675 246 5 Society Society NNP 10_1101-2021_01_07_425675 246 6 for for IN 10_1101-2021_01_07_425675 246 7 Mass Mass NNP 10_1101-2021_01_07_425675 246 8 Spectrometry Spectrometry NNP 10_1101-2021_01_07_425675 246 9 2017 2017 CD 10_1101-2021_01_07_425675 246 10 , , , 10_1101-2021_01_07_425675 246 11 28 28 CD 10_1101-2021_01_07_425675 246 12 ( ( -LRB- 10_1101-2021_01_07_425675 246 13 5 5 CD 10_1101-2021_01_07_425675 246 14 ) ) -RRB- 10_1101-2021_01_07_425675 246 15 , , , 10_1101-2021_01_07_425675 246 16 803 803 CD 10_1101-2021_01_07_425675 246 17 - - SYM 10_1101-2021_01_07_425675 246 18 810 810 CD 10_1101-2021_01_07_425675 246 19 . . . 10_1101-2021_01_07_425675 247 1 414 414 CD 10_1101-2021_01_07_425675 247 2 22 22 CD 10_1101-2021_01_07_425675 247 3 . . . 10_1101-2021_01_07_425675 248 1 Sousa Sousa NNP 10_1101-2021_01_07_425675 248 2 , , , 10_1101-2021_01_07_425675 248 3 E. E. NNP 10_1101-2021_01_07_425675 248 4 ; ; : 10_1101-2021_01_07_425675 248 5 Olland Olland NNP 10_1101-2021_01_07_425675 248 6 , , , 10_1101-2021_01_07_425675 248 7 S. S. NNP 10_1101-2021_01_07_425675 248 8 ; ; : 10_1101-2021_01_07_425675 248 9 Shih Shih NNP 10_1101-2021_01_07_425675 248 10 , , , 10_1101-2021_01_07_425675 248 11 H. H. NNP 10_1101-2021_01_07_425675 248 12 H. H. NNP 10_1101-2021_01_07_425675 248 13 ; ; : 10_1101-2021_01_07_425675 248 14 Marquette Marquette NNP 10_1101-2021_01_07_425675 248 15 , , , 10_1101-2021_01_07_425675 248 16 K. K. NNP 10_1101-2021_01_07_425675 248 17 ; ; : 10_1101-2021_01_07_425675 248 18 Martone Martone NNP 10_1101-2021_01_07_425675 248 19 , , , 10_1101-2021_01_07_425675 248 20 R. R. NNP 10_1101-2021_01_07_425675 248 21 ; ; : 10_1101-2021_01_07_425675 248 22 Lu Lu NNP 10_1101-2021_01_07_425675 248 23 , , , 10_1101-2021_01_07_425675 248 24 Z. Z. NNP 10_1101-2021_01_07_425675 248 25 ; ; : 10_1101-2021_01_07_425675 248 26 Paulsen Paulsen NNP 10_1101-2021_01_07_425675 248 27 , , , 10_1101-2021_01_07_425675 248 28 J. J. NNP 10_1101-2021_01_07_425675 248 29 ; ; : 10_1101-2021_01_07_425675 248 30 Gill Gill NNP 10_1101-2021_01_07_425675 248 31 , , , 10_1101-2021_01_07_425675 248 32 415 415 CD 10_1101-2021_01_07_425675 248 33 D. D. NNP 10_1101-2021_01_07_425675 248 34 ; ; : 10_1101-2021_01_07_425675 248 35 He -PRON- PRP 10_1101-2021_01_07_425675 248 36 , , , 10_1101-2021_01_07_425675 248 37 T. t. NN 10_1101-2021_01_07_425675 248 38 , , , 10_1101-2021_01_07_425675 248 39 Primary primary JJ 10_1101-2021_01_07_425675 248 40 sequence sequence NN 10_1101-2021_01_07_425675 248 41 determination determination NN 10_1101-2021_01_07_425675 248 42 of of IN 10_1101-2021_01_07_425675 248 43 a a DT 10_1101-2021_01_07_425675 248 44 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 248 45 antibody antibody NN 10_1101-2021_01_07_425675 248 46 against against IN 10_1101-2021_01_07_425675 248 47 α α NNP 10_1101-2021_01_07_425675 248 48 - - HYPH 10_1101-2021_01_07_425675 248 49 synuclein synuclein NNP 10_1101-2021_01_07_425675 248 50 using use VBG 10_1101-2021_01_07_425675 248 51 416 416 CD 10_1101-2021_01_07_425675 248 52 a a DT 10_1101-2021_01_07_425675 248 53 novel novel JJ 10_1101-2021_01_07_425675 248 54 mass mass NN 10_1101-2021_01_07_425675 248 55 spectrometry spectrometry NN 10_1101-2021_01_07_425675 248 56 - - HYPH 10_1101-2021_01_07_425675 248 57 based base VBN 10_1101-2021_01_07_425675 248 58 approach approach NN 10_1101-2021_01_07_425675 248 59 . . . 10_1101-2021_01_07_425675 249 1 International International NNP 10_1101-2021_01_07_425675 249 2 Journal Journal NNP 10_1101-2021_01_07_425675 249 3 of of IN 10_1101-2021_01_07_425675 249 4 Mass Mass NNP 10_1101-2021_01_07_425675 249 5 Spectrometry Spectrometry NNP 10_1101-2021_01_07_425675 249 6 2012 2012 CD 10_1101-2021_01_07_425675 249 7 , , , 10_1101-2021_01_07_425675 249 8 417 417 CD 10_1101-2021_01_07_425675 249 9 312 312 CD 10_1101-2021_01_07_425675 249 10 , , , 10_1101-2021_01_07_425675 249 11 61 61 CD 10_1101-2021_01_07_425675 249 12 - - SYM 10_1101-2021_01_07_425675 249 13 69 69 CD 10_1101-2021_01_07_425675 249 14 . . . 10_1101-2021_01_07_425675 250 1 418 418 CD 10_1101-2021_01_07_425675 250 2 23 23 CD 10_1101-2021_01_07_425675 250 3 . . . 10_1101-2021_01_07_425675 251 1 Tran Tran NNP 10_1101-2021_01_07_425675 251 2 , , , 10_1101-2021_01_07_425675 251 3 N. N. NNP 10_1101-2021_01_07_425675 251 4 H. H. NNP 10_1101-2021_01_07_425675 251 5 ; ; : 10_1101-2021_01_07_425675 251 6 Rahman Rahman NNP 10_1101-2021_01_07_425675 251 7 , , , 10_1101-2021_01_07_425675 251 8 M. M. NNP 10_1101-2021_01_07_425675 251 9 Z. Z. NNP 10_1101-2021_01_07_425675 251 10 ; ; : 10_1101-2021_01_07_425675 251 11 He -PRON- PRP 10_1101-2021_01_07_425675 251 12 , , , 10_1101-2021_01_07_425675 251 13 L. L. NNP 10_1101-2021_01_07_425675 251 14 ; ; : 10_1101-2021_01_07_425675 251 15 Xin Xin NNP 10_1101-2021_01_07_425675 251 16 , , , 10_1101-2021_01_07_425675 251 17 L. L. NNP 10_1101-2021_01_07_425675 251 18 ; ; : 10_1101-2021_01_07_425675 251 19 Shan Shan NNP 10_1101-2021_01_07_425675 251 20 , , , 10_1101-2021_01_07_425675 251 21 B. B. NNP 10_1101-2021_01_07_425675 251 22 ; ; : 10_1101-2021_01_07_425675 251 23 Li Li NNP 10_1101-2021_01_07_425675 251 24 , , , 10_1101-2021_01_07_425675 251 25 M. M. NNP 10_1101-2021_01_07_425675 251 26 , , , 10_1101-2021_01_07_425675 251 27 Complete Complete NNP 10_1101-2021_01_07_425675 251 28 de de NNP 10_1101-2021_01_07_425675 251 29 novo novo NNP 10_1101-2021_01_07_425675 251 30 assembly assembly NN 10_1101-2021_01_07_425675 251 31 419 419 CD 10_1101-2021_01_07_425675 251 32 of of IN 10_1101-2021_01_07_425675 251 33 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 251 34 antibody antibody NN 10_1101-2021_01_07_425675 251 35 sequences sequence NNS 10_1101-2021_01_07_425675 251 36 . . . 10_1101-2021_01_07_425675 252 1 Scientific scientific JJ 10_1101-2021_01_07_425675 252 2 reports report NNS 10_1101-2021_01_07_425675 252 3 2016 2016 CD 10_1101-2021_01_07_425675 252 4 , , , 10_1101-2021_01_07_425675 252 5 6 6 CD 10_1101-2021_01_07_425675 252 6 ( ( -LRB- 10_1101-2021_01_07_425675 252 7 1 1 CD 10_1101-2021_01_07_425675 252 8 ) ) -RRB- 10_1101-2021_01_07_425675 252 9 , , , 10_1101-2021_01_07_425675 252 10 1 1 CD 10_1101-2021_01_07_425675 252 11 - - SYM 10_1101-2021_01_07_425675 252 12 10 10 CD 10_1101-2021_01_07_425675 252 13 . . . 10_1101-2021_01_07_425675 253 1 420 420 CD 10_1101-2021_01_07_425675 253 2 24 24 CD 10_1101-2021_01_07_425675 253 3 . . . 10_1101-2021_01_07_425675 254 1 Brizzard Brizzard NNP 10_1101-2021_01_07_425675 254 2 , , , 10_1101-2021_01_07_425675 254 3 B. B. NNP 10_1101-2021_01_07_425675 254 4 L. L. NNP 10_1101-2021_01_07_425675 254 5 ; ; : 10_1101-2021_01_07_425675 254 6 Chubet Chubet NNP 10_1101-2021_01_07_425675 254 7 , , , 10_1101-2021_01_07_425675 254 8 R. R. NNP 10_1101-2021_01_07_425675 254 9 G. G. NNP 10_1101-2021_01_07_425675 254 10 ; ; : 10_1101-2021_01_07_425675 254 11 Vizard Vizard NNP 10_1101-2021_01_07_425675 254 12 , , , 10_1101-2021_01_07_425675 254 13 D. D. NNP 10_1101-2021_01_07_425675 254 14 , , , 10_1101-2021_01_07_425675 254 15 Immunoaffinity Immunoaffinity NNP 10_1101-2021_01_07_425675 254 16 purification purification NN 10_1101-2021_01_07_425675 254 17 of of IN 10_1101-2021_01_07_425675 254 18 FLAG FLAG NNP 10_1101-2021_01_07_425675 254 19 epitope-421 epitope-421 XX 10_1101-2021_01_07_425675 254 20 tagged tag VBN 10_1101-2021_01_07_425675 254 21 bacterial bacterial JJ 10_1101-2021_01_07_425675 254 22 alkaline alkaline NN 10_1101-2021_01_07_425675 254 23 phosphatase phosphatase NN 10_1101-2021_01_07_425675 254 24 using use VBG 10_1101-2021_01_07_425675 254 25 a a DT 10_1101-2021_01_07_425675 254 26 novel novel JJ 10_1101-2021_01_07_425675 254 27 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 254 28 antibody antibody NN 10_1101-2021_01_07_425675 254 29 and and CC 10_1101-2021_01_07_425675 254 30 peptide peptide JJ 10_1101-2021_01_07_425675 254 31 elution elution NN 10_1101-2021_01_07_425675 254 32 . . . 10_1101-2021_01_07_425675 255 1 422 422 CD 10_1101-2021_01_07_425675 255 2 Biotechniques biotechnique NNS 10_1101-2021_01_07_425675 255 3 1994 1994 CD 10_1101-2021_01_07_425675 255 4 , , , 10_1101-2021_01_07_425675 255 5 16 16 CD 10_1101-2021_01_07_425675 255 6 ( ( -LRB- 10_1101-2021_01_07_425675 255 7 4 4 CD 10_1101-2021_01_07_425675 255 8 ) ) -RRB- 10_1101-2021_01_07_425675 255 9 , , , 10_1101-2021_01_07_425675 255 10 730 730 CD 10_1101-2021_01_07_425675 255 11 - - SYM 10_1101-2021_01_07_425675 255 12 735 735 CD 10_1101-2021_01_07_425675 255 13 . . . 10_1101-2021_01_07_425675 256 1 423 423 CD 10_1101-2021_01_07_425675 256 2 25 25 CD 10_1101-2021_01_07_425675 256 3 . . . 10_1101-2021_01_07_425675 257 1 Sigma Sigma NNP 10_1101-2021_01_07_425675 257 2 - - HYPH 10_1101-2021_01_07_425675 257 3 Aldrich Aldrich NNP 10_1101-2021_01_07_425675 257 4 anti anti JJ 10_1101-2021_01_07_425675 257 5 - - JJ 10_1101-2021_01_07_425675 257 6 FLAG FLAG NNP 10_1101-2021_01_07_425675 257 7 - - HYPH 10_1101-2021_01_07_425675 257 8 M2 M2 NNP 10_1101-2021_01_07_425675 257 9 F1804 f1804 NN 10_1101-2021_01_07_425675 257 10 product product NN 10_1101-2021_01_07_425675 257 11 page page NN 10_1101-2021_01_07_425675 257 12 . . . 10_1101-2021_01_07_425675 258 1 424 424 CD 10_1101-2021_01_07_425675 258 2 https://www.sigmaaldrich.com/catalog/product/sigma/f1804?lang=en®ion=NL https://www.sigmaaldrich.com/catalog/product/sigma/f1804?lang=en®ion=nl RB 10_1101-2021_01_07_425675 258 3 ( ( -LRB- 10_1101-2021_01_07_425675 258 4 accessed access VBN 10_1101-2021_01_07_425675 258 5 05 05 CD 10_1101-2021_01_07_425675 258 6 - - SYM 10_1101-2021_01_07_425675 258 7 425 425 CD 10_1101-2021_01_07_425675 258 8 01 01 CD 10_1101-2021_01_07_425675 258 9 - - SYM 10_1101-2021_01_07_425675 258 10 2021 2021 CD 10_1101-2021_01_07_425675 258 11 ) ) -RRB- 10_1101-2021_01_07_425675 258 12 . . . 10_1101-2021_01_07_425675 259 1 426 426 CD 10_1101-2021_01_07_425675 259 2 26 26 CD 10_1101-2021_01_07_425675 259 3 . . . 10_1101-2021_01_07_425675 260 1 Paizs Paizs NNP 10_1101-2021_01_07_425675 260 2 , , , 10_1101-2021_01_07_425675 260 3 B. B. NNP 10_1101-2021_01_07_425675 260 4 ; ; : 10_1101-2021_01_07_425675 260 5 Suhai Suhai NNP 10_1101-2021_01_07_425675 260 6 , , , 10_1101-2021_01_07_425675 260 7 S. S. NNP 10_1101-2021_01_07_425675 260 8 , , , 10_1101-2021_01_07_425675 260 9 Fragmentation Fragmentation NNP 10_1101-2021_01_07_425675 260 10 pathways pathway NNS 10_1101-2021_01_07_425675 260 11 of of IN 10_1101-2021_01_07_425675 260 12 protonated protonate VBN 10_1101-2021_01_07_425675 260 13 peptides peptide NNS 10_1101-2021_01_07_425675 260 14 . . . 10_1101-2021_01_07_425675 261 1 Mass Mass NNP 10_1101-2021_01_07_425675 261 2 427 427 CD 10_1101-2021_01_07_425675 261 3 spectrometry spectrometry NN 10_1101-2021_01_07_425675 261 4 reviews review NNS 10_1101-2021_01_07_425675 261 5 2005 2005 CD 10_1101-2021_01_07_425675 261 6 , , , 10_1101-2021_01_07_425675 261 7 24 24 CD 10_1101-2021_01_07_425675 261 8 ( ( -LRB- 10_1101-2021_01_07_425675 261 9 4 4 CD 10_1101-2021_01_07_425675 261 10 ) ) -RRB- 10_1101-2021_01_07_425675 261 11 , , , 10_1101-2021_01_07_425675 261 12 508 508 CD 10_1101-2021_01_07_425675 261 13 - - SYM 10_1101-2021_01_07_425675 261 14 548 548 CD 10_1101-2021_01_07_425675 261 15 . . . 10_1101-2021_01_07_425675 262 1 428 428 CD 10_1101-2021_01_07_425675 262 2 27 27 CD 10_1101-2021_01_07_425675 262 3 . . . 10_1101-2021_01_07_425675 263 1 Diedrich Diedrich NNP 10_1101-2021_01_07_425675 263 2 , , , 10_1101-2021_01_07_425675 263 3 J. J. NNP 10_1101-2021_01_07_425675 263 4 K. K. NNP 10_1101-2021_01_07_425675 263 5 ; ; : 10_1101-2021_01_07_425675 263 6 Pinto Pinto NNP 10_1101-2021_01_07_425675 263 7 , , , 10_1101-2021_01_07_425675 263 8 A. a. NN 10_1101-2021_01_07_425675 263 9 F. F. NNP 10_1101-2021_01_07_425675 263 10 ; ; : 10_1101-2021_01_07_425675 263 11 Yates Yates NNP 10_1101-2021_01_07_425675 263 12 III III NNP 10_1101-2021_01_07_425675 263 13 , , , 10_1101-2021_01_07_425675 263 14 J. J. NNP 10_1101-2021_01_07_425675 263 15 R. R. NNP 10_1101-2021_01_07_425675 263 16 , , , 10_1101-2021_01_07_425675 263 17 Energy Energy NNP 10_1101-2021_01_07_425675 263 18 dependence dependence NN 10_1101-2021_01_07_425675 263 19 of of IN 10_1101-2021_01_07_425675 263 20 HCD HCD NNP 10_1101-2021_01_07_425675 263 21 on on IN 10_1101-2021_01_07_425675 263 22 peptide peptide NN 10_1101-2021_01_07_425675 263 23 429 429 CD 10_1101-2021_01_07_425675 263 24 fragmentation fragmentation NN 10_1101-2021_01_07_425675 263 25 : : : 10_1101-2021_01_07_425675 263 26 stepped step VBN 10_1101-2021_01_07_425675 263 27 collisional collisional JJ 10_1101-2021_01_07_425675 263 28 energy energy NN 10_1101-2021_01_07_425675 263 29 finds find VBZ 10_1101-2021_01_07_425675 263 30 the the DT 10_1101-2021_01_07_425675 263 31 sweet sweet JJ 10_1101-2021_01_07_425675 263 32 spot spot NN 10_1101-2021_01_07_425675 263 33 . . . 10_1101-2021_01_07_425675 264 1 Journal Journal NNP 10_1101-2021_01_07_425675 264 2 of of IN 10_1101-2021_01_07_425675 264 3 the the DT 10_1101-2021_01_07_425675 264 4 American American NNP 10_1101-2021_01_07_425675 264 5 Society Society NNP 10_1101-2021_01_07_425675 264 6 430 430 CD 10_1101-2021_01_07_425675 264 7 for for IN 10_1101-2021_01_07_425675 264 8 Mass Mass NNP 10_1101-2021_01_07_425675 264 9 Spectrometry Spectrometry NNP 10_1101-2021_01_07_425675 264 10 2013 2013 CD 10_1101-2021_01_07_425675 264 11 , , , 10_1101-2021_01_07_425675 264 12 24 24 CD 10_1101-2021_01_07_425675 264 13 ( ( -LRB- 10_1101-2021_01_07_425675 264 14 11 11 CD 10_1101-2021_01_07_425675 264 15 ) ) -RRB- 10_1101-2021_01_07_425675 264 16 , , , 10_1101-2021_01_07_425675 264 17 1690 1690 CD 10_1101-2021_01_07_425675 264 18 - - SYM 10_1101-2021_01_07_425675 264 19 1699 1699 CD 10_1101-2021_01_07_425675 264 20 . . . 10_1101-2021_01_07_425675 265 1 431 431 CD 10_1101-2021_01_07_425675 265 2 28 28 CD 10_1101-2021_01_07_425675 265 3 . . . 10_1101-2021_01_07_425675 266 1 Frese Frese NNP 10_1101-2021_01_07_425675 266 2 , , , 10_1101-2021_01_07_425675 266 3 C. C. NNP 10_1101-2021_01_07_425675 266 4 K. K. NNP 10_1101-2021_01_07_425675 266 5 ; ; : 10_1101-2021_01_07_425675 266 6 Altelaar Altelaar NNP 10_1101-2021_01_07_425675 266 7 , , , 10_1101-2021_01_07_425675 266 8 A. A. NNP 10_1101-2021_01_07_425675 266 9 M. M. NNP 10_1101-2021_01_07_425675 266 10 ; ; : 10_1101-2021_01_07_425675 266 11 van van NNP 10_1101-2021_01_07_425675 266 12 den den NNP 10_1101-2021_01_07_425675 266 13 Toorn Toorn NNP 10_1101-2021_01_07_425675 266 14 , , , 10_1101-2021_01_07_425675 266 15 H. H. NNP 10_1101-2021_01_07_425675 266 16 ; ; : 10_1101-2021_01_07_425675 266 17 Nolting Nolting NNP 10_1101-2021_01_07_425675 266 18 , , , 10_1101-2021_01_07_425675 266 19 D. D. NNP 10_1101-2021_01_07_425675 266 20 ; ; : 10_1101-2021_01_07_425675 266 21 Griep Griep NNP 10_1101-2021_01_07_425675 266 22 - - HYPH 10_1101-2021_01_07_425675 266 23 Raming Raming NNP 10_1101-2021_01_07_425675 266 24 , , , 10_1101-2021_01_07_425675 266 25 J. J. NNP 10_1101-2021_01_07_425675 266 26 ; ; : 10_1101-2021_01_07_425675 266 27 Heck Heck NNP 10_1101-2021_01_07_425675 266 28 , , , 10_1101-2021_01_07_425675 266 29 A. a. NN 10_1101-2021_01_07_425675 267 1 432 432 CD 10_1101-2021_01_07_425675 267 2 J. J. NNP 10_1101-2021_01_07_425675 267 3 ; ; : 10_1101-2021_01_07_425675 267 4 Mohammed Mohammed NNP 10_1101-2021_01_07_425675 267 5 , , , 10_1101-2021_01_07_425675 267 6 S. S. NNP 10_1101-2021_01_07_425675 267 7 , , , 10_1101-2021_01_07_425675 267 8 Toward toward IN 10_1101-2021_01_07_425675 267 9 full full JJ 10_1101-2021_01_07_425675 267 10 peptide peptide NN 10_1101-2021_01_07_425675 267 11 sequence sequence NN 10_1101-2021_01_07_425675 267 12 coverage coverage NN 10_1101-2021_01_07_425675 267 13 by by IN 10_1101-2021_01_07_425675 267 14 dual dual JJ 10_1101-2021_01_07_425675 267 15 fragmentation fragmentation NN 10_1101-2021_01_07_425675 267 16 combining combine VBG 10_1101-2021_01_07_425675 267 17 433 433 CD 10_1101-2021_01_07_425675 267 18 electron electron NN 10_1101-2021_01_07_425675 267 19 - - HYPH 10_1101-2021_01_07_425675 267 20 transfer transfer NN 10_1101-2021_01_07_425675 267 21 and and CC 10_1101-2021_01_07_425675 267 22 higher high JJR 10_1101-2021_01_07_425675 267 23 - - HYPH 10_1101-2021_01_07_425675 267 24 energy energy NN 10_1101-2021_01_07_425675 267 25 collision collision NN 10_1101-2021_01_07_425675 267 26 dissociation dissociation NN 10_1101-2021_01_07_425675 267 27 tandem tandem NNP 10_1101-2021_01_07_425675 267 28 mass mass NNP 10_1101-2021_01_07_425675 267 29 spectrometry spectrometry NNP 10_1101-2021_01_07_425675 267 30 . . . 10_1101-2021_01_07_425675 268 1 Analytical analytical JJ 10_1101-2021_01_07_425675 268 2 434 434 CD 10_1101-2021_01_07_425675 268 3 chemistry chemistry NN 10_1101-2021_01_07_425675 268 4 2012 2012 CD 10_1101-2021_01_07_425675 268 5 , , , 10_1101-2021_01_07_425675 268 6 84 84 CD 10_1101-2021_01_07_425675 268 7 ( ( -LRB- 10_1101-2021_01_07_425675 268 8 22 22 CD 10_1101-2021_01_07_425675 268 9 ) ) -RRB- 10_1101-2021_01_07_425675 268 10 , , , 10_1101-2021_01_07_425675 268 11 9668 9668 CD 10_1101-2021_01_07_425675 268 12 - - SYM 10_1101-2021_01_07_425675 268 13 9673 9673 CD 10_1101-2021_01_07_425675 268 14 . . . 10_1101-2021_01_07_425675 269 1 435 435 CD 10_1101-2021_01_07_425675 269 2 29 29 CD 10_1101-2021_01_07_425675 269 3 . . . 10_1101-2021_01_07_425675 270 1 Frese Frese NNP 10_1101-2021_01_07_425675 270 2 , , , 10_1101-2021_01_07_425675 270 3 C. C. NNP 10_1101-2021_01_07_425675 270 4 K. K. NNP 10_1101-2021_01_07_425675 270 5 ; ; : 10_1101-2021_01_07_425675 270 6 Zhou Zhou NNP 10_1101-2021_01_07_425675 270 7 , , , 10_1101-2021_01_07_425675 270 8 H. H. NNP 10_1101-2021_01_07_425675 270 9 ; ; : 10_1101-2021_01_07_425675 270 10 Taus Taus NNP 10_1101-2021_01_07_425675 270 11 , , , 10_1101-2021_01_07_425675 270 12 T. t. NN 10_1101-2021_01_07_425675 270 13 ; ; : 10_1101-2021_01_07_425675 270 14 Altelaar Altelaar NNP 10_1101-2021_01_07_425675 270 15 , , , 10_1101-2021_01_07_425675 270 16 A. a. NN 10_1101-2021_01_07_425675 270 17 M. M. NNP 10_1101-2021_01_07_425675 270 18 ; ; : 10_1101-2021_01_07_425675 270 19 Mechtler Mechtler NNP 10_1101-2021_01_07_425675 270 20 , , , 10_1101-2021_01_07_425675 270 21 K. K. NNP 10_1101-2021_01_07_425675 270 22 ; ; : 10_1101-2021_01_07_425675 270 23 Heck heck UH 10_1101-2021_01_07_425675 270 24 , , , 10_1101-2021_01_07_425675 270 25 A. A. NNP 10_1101-2021_01_07_425675 270 26 J. J. NNP 10_1101-2021_01_07_425675 270 27 ; ; : 10_1101-2021_01_07_425675 270 28 Mohammed Mohammed NNP 10_1101-2021_01_07_425675 270 29 , , , 10_1101-2021_01_07_425675 270 30 436 436 CD 10_1101-2021_01_07_425675 270 31 S. S. NNP 10_1101-2021_01_07_425675 270 32 , , , 10_1101-2021_01_07_425675 270 33 Unambiguous unambiguous JJ 10_1101-2021_01_07_425675 270 34 phosphosite phosphosite NN 10_1101-2021_01_07_425675 270 35 localization localization NN 10_1101-2021_01_07_425675 270 36 using use VBG 10_1101-2021_01_07_425675 270 37 electron electron NN 10_1101-2021_01_07_425675 270 38 - - HYPH 10_1101-2021_01_07_425675 270 39 transfer transfer NN 10_1101-2021_01_07_425675 270 40 / / SYM 10_1101-2021_01_07_425675 270 41 higher high JJR 10_1101-2021_01_07_425675 270 42 - - HYPH 10_1101-2021_01_07_425675 270 43 energy energy NN 10_1101-2021_01_07_425675 270 44 collision collision NN 10_1101-2021_01_07_425675 270 45 437 437 CD 10_1101-2021_01_07_425675 270 46 dissociation dissociation NN 10_1101-2021_01_07_425675 270 47 ( ( -LRB- 10_1101-2021_01_07_425675 270 48 EThcD EThcD NNP 10_1101-2021_01_07_425675 270 49 ) ) -RRB- 10_1101-2021_01_07_425675 270 50 . . . 10_1101-2021_01_07_425675 271 1 Journal Journal NNP 10_1101-2021_01_07_425675 271 2 of of IN 10_1101-2021_01_07_425675 271 3 proteome proteome NNP 10_1101-2021_01_07_425675 271 4 research research NN 10_1101-2021_01_07_425675 271 5 2013 2013 CD 10_1101-2021_01_07_425675 271 6 , , , 10_1101-2021_01_07_425675 271 7 12 12 CD 10_1101-2021_01_07_425675 271 8 ( ( -LRB- 10_1101-2021_01_07_425675 271 9 3 3 CD 10_1101-2021_01_07_425675 271 10 ) ) -RRB- 10_1101-2021_01_07_425675 271 11 , , , 10_1101-2021_01_07_425675 271 12 1520 1520 CD 10_1101-2021_01_07_425675 271 13 - - SYM 10_1101-2021_01_07_425675 271 14 1525 1525 CD 10_1101-2021_01_07_425675 271 15 . . . 10_1101-2021_01_07_425675 272 1 438 438 CD 10_1101-2021_01_07_425675 272 2 30 30 CD 10_1101-2021_01_07_425675 272 3 . . . 10_1101-2021_01_07_425675 273 1 Carter Carter NNP 10_1101-2021_01_07_425675 273 2 , , , 10_1101-2021_01_07_425675 273 3 P. P. NNP 10_1101-2021_01_07_425675 273 4 ; ; : 10_1101-2021_01_07_425675 273 5 Presta Presta NNP 10_1101-2021_01_07_425675 273 6 , , , 10_1101-2021_01_07_425675 273 7 L. L. NNP 10_1101-2021_01_07_425675 273 8 ; ; : 10_1101-2021_01_07_425675 273 9 Gorman Gorman NNP 10_1101-2021_01_07_425675 273 10 , , , 10_1101-2021_01_07_425675 273 11 C. C. NNP 10_1101-2021_01_07_425675 273 12 M. M. NNP 10_1101-2021_01_07_425675 273 13 ; ; : 10_1101-2021_01_07_425675 273 14 Ridgway Ridgway NNP 10_1101-2021_01_07_425675 273 15 , , , 10_1101-2021_01_07_425675 273 16 J. J. NNP 10_1101-2021_01_07_425675 273 17 ; ; : 10_1101-2021_01_07_425675 273 18 Henner Henner NNP 10_1101-2021_01_07_425675 273 19 , , , 10_1101-2021_01_07_425675 273 20 D. D. NNP 10_1101-2021_01_07_425675 273 21 ; ; : 10_1101-2021_01_07_425675 273 22 Wong Wong NNP 10_1101-2021_01_07_425675 273 23 , , , 10_1101-2021_01_07_425675 273 24 W. W. NNP 10_1101-2021_01_07_425675 273 25 ; ; : 10_1101-2021_01_07_425675 273 26 Rowland Rowland NNP 10_1101-2021_01_07_425675 273 27 , , , 10_1101-2021_01_07_425675 273 28 A. a. NN 10_1101-2021_01_07_425675 274 1 439 439 CD 10_1101-2021_01_07_425675 274 2 M. M. NNP 10_1101-2021_01_07_425675 274 3 ; ; : 10_1101-2021_01_07_425675 274 4 Kotts Kotts NNP 10_1101-2021_01_07_425675 274 5 , , , 10_1101-2021_01_07_425675 274 6 C. C. NNP 10_1101-2021_01_07_425675 274 7 ; ; : 10_1101-2021_01_07_425675 274 8 Carver Carver NNP 10_1101-2021_01_07_425675 274 9 , , , 10_1101-2021_01_07_425675 274 10 M. M. NNP 10_1101-2021_01_07_425675 274 11 E. E. NNP 10_1101-2021_01_07_425675 274 12 ; ; : 10_1101-2021_01_07_425675 274 13 Shepard Shepard NNP 10_1101-2021_01_07_425675 274 14 , , , 10_1101-2021_01_07_425675 274 15 H. H. NNP 10_1101-2021_01_07_425675 274 16 M. M. NNP 10_1101-2021_01_07_425675 274 17 , , , 10_1101-2021_01_07_425675 274 18 Humanization Humanization NNP 10_1101-2021_01_07_425675 274 19 of of IN 10_1101-2021_01_07_425675 274 20 an an DT 10_1101-2021_01_07_425675 274 21 anti anti NN 10_1101-2021_01_07_425675 274 22 - - JJ 10_1101-2021_01_07_425675 274 23 p185HER2 p185her2 JJ 10_1101-2021_01_07_425675 274 24 antibody antibody NN 10_1101-2021_01_07_425675 274 25 for for IN 10_1101-2021_01_07_425675 274 26 440 440 CD 10_1101-2021_01_07_425675 274 27 human human JJ 10_1101-2021_01_07_425675 274 28 cancer cancer NN 10_1101-2021_01_07_425675 274 29 therapy therapy NN 10_1101-2021_01_07_425675 274 30 . . . 10_1101-2021_01_07_425675 275 1 Proceedings proceeding NNS 10_1101-2021_01_07_425675 275 2 of of IN 10_1101-2021_01_07_425675 275 3 the the DT 10_1101-2021_01_07_425675 275 4 National National NNP 10_1101-2021_01_07_425675 275 5 Academy Academy NNP 10_1101-2021_01_07_425675 275 6 of of IN 10_1101-2021_01_07_425675 275 7 Sciences Sciences NNPS 10_1101-2021_01_07_425675 275 8 1992 1992 CD 10_1101-2021_01_07_425675 275 9 , , , 10_1101-2021_01_07_425675 275 10 89 89 CD 10_1101-2021_01_07_425675 275 11 ( ( -LRB- 10_1101-2021_01_07_425675 275 12 10 10 CD 10_1101-2021_01_07_425675 275 13 ) ) -RRB- 10_1101-2021_01_07_425675 275 14 , , , 10_1101-2021_01_07_425675 275 15 4285 4285 CD 10_1101-2021_01_07_425675 275 16 - - SYM 10_1101-2021_01_07_425675 275 17 441 441 CD 10_1101-2021_01_07_425675 275 18 4289 4289 CD 10_1101-2021_01_07_425675 275 19 . . . 10_1101-2021_01_07_425675 276 1 442 442 CD 10_1101-2021_01_07_425675 276 2 31 31 CD 10_1101-2021_01_07_425675 276 3 . . . 10_1101-2021_01_07_425675 277 1 Slamon Slamon NNP 10_1101-2021_01_07_425675 277 2 , , , 10_1101-2021_01_07_425675 277 3 D. D. NNP 10_1101-2021_01_07_425675 277 4 J. J. NNP 10_1101-2021_01_07_425675 277 5 ; ; : 10_1101-2021_01_07_425675 277 6 Leyland Leyland NNP 10_1101-2021_01_07_425675 277 7 - - HYPH 10_1101-2021_01_07_425675 277 8 Jones Jones NNP 10_1101-2021_01_07_425675 277 9 , , , 10_1101-2021_01_07_425675 277 10 B. B. NNP 10_1101-2021_01_07_425675 277 11 ; ; : 10_1101-2021_01_07_425675 277 12 Shak Shak NNP 10_1101-2021_01_07_425675 277 13 , , , 10_1101-2021_01_07_425675 277 14 S. S. NNP 10_1101-2021_01_07_425675 277 15 ; ; : 10_1101-2021_01_07_425675 277 16 Fuchs Fuchs NNP 10_1101-2021_01_07_425675 277 17 , , , 10_1101-2021_01_07_425675 277 18 H. H. NNP 10_1101-2021_01_07_425675 277 19 ; ; : 10_1101-2021_01_07_425675 277 20 Paton Paton NNP 10_1101-2021_01_07_425675 277 21 , , , 10_1101-2021_01_07_425675 277 22 V. V. NNP 10_1101-2021_01_07_425675 277 23 ; ; : 10_1101-2021_01_07_425675 277 24 Bajamonde Bajamonde NNP 10_1101-2021_01_07_425675 277 25 , , , 10_1101-2021_01_07_425675 277 26 A. a. NN 10_1101-2021_01_07_425675 277 27 ; ; : 10_1101-2021_01_07_425675 277 28 443 443 CD 10_1101-2021_01_07_425675 277 29 Fleming Fleming NNP 10_1101-2021_01_07_425675 277 30 , , , 10_1101-2021_01_07_425675 277 31 T. T. NNP 10_1101-2021_01_07_425675 277 32 ; ; : 10_1101-2021_01_07_425675 277 33 Eiermann Eiermann NNP 10_1101-2021_01_07_425675 277 34 , , , 10_1101-2021_01_07_425675 277 35 W. W. NNP 10_1101-2021_01_07_425675 277 36 ; ; : 10_1101-2021_01_07_425675 277 37 Wolter Wolter NNP 10_1101-2021_01_07_425675 277 38 , , , 10_1101-2021_01_07_425675 277 39 J. J. NNP 10_1101-2021_01_07_425675 277 40 ; ; : 10_1101-2021_01_07_425675 277 41 Pegram Pegram NNP 10_1101-2021_01_07_425675 277 42 , , , 10_1101-2021_01_07_425675 277 43 M. M. NNP 10_1101-2021_01_07_425675 277 44 , , , 10_1101-2021_01_07_425675 277 45 Use Use NNP 10_1101-2021_01_07_425675 277 46 of of IN 10_1101-2021_01_07_425675 277 47 chemotherapy chemotherapy NN 10_1101-2021_01_07_425675 277 48 plus plus CC 10_1101-2021_01_07_425675 277 49 a a DT 10_1101-2021_01_07_425675 277 50 monoclonal monoclonal JJ 10_1101-2021_01_07_425675 277 51 444 444 CD 10_1101-2021_01_07_425675 277 52 antibody antibody NN 10_1101-2021_01_07_425675 277 53 against against IN 10_1101-2021_01_07_425675 277 54 HER2 HER2 NNP 10_1101-2021_01_07_425675 277 55 for for IN 10_1101-2021_01_07_425675 277 56 metastatic metastatic JJ 10_1101-2021_01_07_425675 277 57 breast breast NN 10_1101-2021_01_07_425675 277 58 cancer cancer NN 10_1101-2021_01_07_425675 277 59 that that WDT 10_1101-2021_01_07_425675 277 60 overexpresses overexpresse VBZ 10_1101-2021_01_07_425675 277 61 HER2 HER2 NNP 10_1101-2021_01_07_425675 277 62 . . . 10_1101-2021_01_07_425675 278 1 New New NNP 10_1101-2021_01_07_425675 278 2 England England NNP 10_1101-2021_01_07_425675 278 3 445 445 CD 10_1101-2021_01_07_425675 278 4 journal journal NN 10_1101-2021_01_07_425675 278 5 of of IN 10_1101-2021_01_07_425675 278 6 medicine medicine NNP 10_1101-2021_01_07_425675 278 7 2001 2001 CD 10_1101-2021_01_07_425675 278 8 , , , 10_1101-2021_01_07_425675 278 9 344 344 CD 10_1101-2021_01_07_425675 278 10 ( ( -LRB- 10_1101-2021_01_07_425675 278 11 11 11 CD 10_1101-2021_01_07_425675 278 12 ) ) -RRB- 10_1101-2021_01_07_425675 278 13 , , , 10_1101-2021_01_07_425675 278 14 783 783 CD 10_1101-2021_01_07_425675 278 15 - - SYM 10_1101-2021_01_07_425675 278 16 792 792 CD 10_1101-2021_01_07_425675 278 17 . . . 10_1101-2021_01_07_425675 279 1 446 446 CD 10_1101-2021_01_07_425675 279 2 32 32 CD 10_1101-2021_01_07_425675 279 3 . . . 10_1101-2021_01_07_425675 280 1 Einhauer einhauer VB 10_1101-2021_01_07_425675 280 2 , , , 10_1101-2021_01_07_425675 280 3 A. a. NN 10_1101-2021_01_07_425675 280 4 ; ; : 10_1101-2021_01_07_425675 280 5 Jungbauer Jungbauer NNP 10_1101-2021_01_07_425675 280 6 , , , 10_1101-2021_01_07_425675 280 7 A. a. NN 10_1101-2021_01_07_425675 280 8 , , , 10_1101-2021_01_07_425675 280 9 The the DT 10_1101-2021_01_07_425675 280 10 FLAG FLAG NNP 10_1101-2021_01_07_425675 280 11 ™ ™ CD 10_1101-2021_01_07_425675 280 12 peptide peptide NN 10_1101-2021_01_07_425675 280 13 , , , 10_1101-2021_01_07_425675 280 14 a a DT 10_1101-2021_01_07_425675 280 15 versatile versatile JJ 10_1101-2021_01_07_425675 280 16 fusion fusion NN 10_1101-2021_01_07_425675 280 17 tag tag NN 10_1101-2021_01_07_425675 280 18 for for IN 10_1101-2021_01_07_425675 280 19 the the DT 10_1101-2021_01_07_425675 280 20 447 447 CD 10_1101-2021_01_07_425675 280 21 purification purification NN 10_1101-2021_01_07_425675 280 22 of of IN 10_1101-2021_01_07_425675 280 23 recombinant recombinant JJ 10_1101-2021_01_07_425675 280 24 proteins protein NNS 10_1101-2021_01_07_425675 280 25 . . . 10_1101-2021_01_07_425675 281 1 Journal Journal NNP 10_1101-2021_01_07_425675 281 2 of of IN 10_1101-2021_01_07_425675 281 3 biochemical biochemical JJ 10_1101-2021_01_07_425675 281 4 and and CC 10_1101-2021_01_07_425675 281 5 biophysical biophysical JJ 10_1101-2021_01_07_425675 281 6 methods method NNS 10_1101-2021_01_07_425675 281 7 2001 2001 CD 10_1101-2021_01_07_425675 281 8 , , , 10_1101-2021_01_07_425675 281 9 49 49 CD 10_1101-2021_01_07_425675 281 10 448 448 CD 10_1101-2021_01_07_425675 281 11 ( ( -LRB- 10_1101-2021_01_07_425675 281 12 1 1 CD 10_1101-2021_01_07_425675 281 13 - - SYM 10_1101-2021_01_07_425675 281 14 3 3 CD 10_1101-2021_01_07_425675 281 15 ) ) -RRB- 10_1101-2021_01_07_425675 281 16 , , , 10_1101-2021_01_07_425675 281 17 455 455 CD 10_1101-2021_01_07_425675 281 18 - - SYM 10_1101-2021_01_07_425675 281 19 465 465 CD 10_1101-2021_01_07_425675 281 20 . . . 10_1101-2021_01_07_425675 282 1 449 449 CD 10_1101-2021_01_07_425675 282 2 .CC .CC NFP 10_1101-2021_01_07_425675 282 3 - - : 10_1101-2021_01_07_425675 282 4 BY by IN 10_1101-2021_01_07_425675 282 5 4.0 4.0 CD 10_1101-2021_01_07_425675 282 6 International International NNP 10_1101-2021_01_07_425675 282 7 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 282 8 under under IN 10_1101-2021_01_07_425675 282 9 a a DT 10_1101-2021_01_07_425675 282 10 ( ( -LRB- 10_1101-2021_01_07_425675 282 11 which which WDT 10_1101-2021_01_07_425675 282 12 was be VBD 10_1101-2021_01_07_425675 282 13 not not RB 10_1101-2021_01_07_425675 282 14 certified certify VBN 10_1101-2021_01_07_425675 282 15 by by IN 10_1101-2021_01_07_425675 282 16 peer peer NN 10_1101-2021_01_07_425675 282 17 review review NN 10_1101-2021_01_07_425675 282 18 ) ) -RRB- 10_1101-2021_01_07_425675 282 19 is be VBZ 10_1101-2021_01_07_425675 282 20 the the DT 10_1101-2021_01_07_425675 282 21 author author NN 10_1101-2021_01_07_425675 282 22 / / SYM 10_1101-2021_01_07_425675 282 23 funder funder NN 10_1101-2021_01_07_425675 282 24 , , , 10_1101-2021_01_07_425675 282 25 who who WP 10_1101-2021_01_07_425675 282 26 has have VBZ 10_1101-2021_01_07_425675 282 27 granted grant VBN 10_1101-2021_01_07_425675 282 28 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 282 29 a a DT 10_1101-2021_01_07_425675 282 30 license license NN 10_1101-2021_01_07_425675 282 31 to to TO 10_1101-2021_01_07_425675 282 32 display display VB 10_1101-2021_01_07_425675 282 33 the the DT 10_1101-2021_01_07_425675 282 34 preprint preprint NN 10_1101-2021_01_07_425675 282 35 in in IN 10_1101-2021_01_07_425675 282 36 perpetuity perpetuity NN 10_1101-2021_01_07_425675 282 37 . . . 10_1101-2021_01_07_425675 283 1 It -PRON- PRP 10_1101-2021_01_07_425675 283 2 is be VBZ 10_1101-2021_01_07_425675 283 3 made make VBN 10_1101-2021_01_07_425675 283 4 The the DT 10_1101-2021_01_07_425675 283 5 copyright copyright NN 10_1101-2021_01_07_425675 283 6 holder holder NN 10_1101-2021_01_07_425675 283 7 for for IN 10_1101-2021_01_07_425675 283 8 this this DT 10_1101-2021_01_07_425675 283 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 283 10 version version NN 10_1101-2021_01_07_425675 283 11 posted post VBD 10_1101-2021_01_07_425675 283 12 January January NNP 10_1101-2021_01_07_425675 283 13 8 8 CD 10_1101-2021_01_07_425675 283 14 , , , 10_1101-2021_01_07_425675 283 15 2021 2021 CD 10_1101-2021_01_07_425675 283 16 . . . 10_1101-2021_01_07_425675 283 17 ; ; : 10_1101-2021_01_07_425675 283 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 283 19 : : : 10_1101-2021_01_07_425675 283 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 283 21 preprint preprint NN 10_1101-2021_01_07_425675 283 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NNP 10_1101-2021_01_07_425675 283 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD 10_1101-2021_01_07_425675 283 24 17 17 CD 10_1101-2021_01_07_425675 283 25 33 33 CD 10_1101-2021_01_07_425675 283 26 . . . 10_1101-2021_01_07_425675 284 1 Roosild roosild VB 10_1101-2021_01_07_425675 284 2 , , , 10_1101-2021_01_07_425675 284 3 T. T. NNP 10_1101-2021_01_07_425675 284 4 P. P. NNP 10_1101-2021_01_07_425675 284 5 ; ; : 10_1101-2021_01_07_425675 284 6 Castronovo Castronovo NNP 10_1101-2021_01_07_425675 284 7 , , , 10_1101-2021_01_07_425675 284 8 S. S. NNP 10_1101-2021_01_07_425675 284 9 ; ; : 10_1101-2021_01_07_425675 284 10 Choe Choe NNP 10_1101-2021_01_07_425675 284 11 , , , 10_1101-2021_01_07_425675 284 12 S. S. NNP 10_1101-2021_01_07_425675 284 13 , , , 10_1101-2021_01_07_425675 284 14 Structure Structure NNP 10_1101-2021_01_07_425675 284 15 of of IN 10_1101-2021_01_07_425675 284 16 anti anti JJ 10_1101-2021_01_07_425675 284 17 - - JJ 10_1101-2021_01_07_425675 284 18 FLAG FLAG NNP 10_1101-2021_01_07_425675 284 19 M2 M2 NNP 10_1101-2021_01_07_425675 284 20 Fab Fab NNP 10_1101-2021_01_07_425675 284 21 domain domain NN 10_1101-2021_01_07_425675 284 22 and and CC 10_1101-2021_01_07_425675 284 23 its -PRON- PRP$ 10_1101-2021_01_07_425675 284 24 450 450 CD 10_1101-2021_01_07_425675 284 25 use use NN 10_1101-2021_01_07_425675 284 26 in in IN 10_1101-2021_01_07_425675 284 27 the the DT 10_1101-2021_01_07_425675 284 28 stabilization stabilization NN 10_1101-2021_01_07_425675 284 29 of of IN 10_1101-2021_01_07_425675 284 30 engineered engineer VBN 10_1101-2021_01_07_425675 284 31 membrane membrane NN 10_1101-2021_01_07_425675 284 32 proteins protein NNS 10_1101-2021_01_07_425675 284 33 . . . 10_1101-2021_01_07_425675 285 1 Acta Acta NNP 10_1101-2021_01_07_425675 285 2 Crystallographica Crystallographica NNP 10_1101-2021_01_07_425675 285 3 Section Section NNP 10_1101-2021_01_07_425675 285 4 F F NNP 10_1101-2021_01_07_425675 285 5 : : : 10_1101-2021_01_07_425675 285 6 451 451 CD 10_1101-2021_01_07_425675 285 7 Structural Structural NNP 10_1101-2021_01_07_425675 285 8 Biology Biology NNP 10_1101-2021_01_07_425675 285 9 and and CC 10_1101-2021_01_07_425675 285 10 Crystallization Crystallization NNP 10_1101-2021_01_07_425675 285 11 Communications Communications NNP 10_1101-2021_01_07_425675 285 12 2006 2006 CD 10_1101-2021_01_07_425675 285 13 , , , 10_1101-2021_01_07_425675 285 14 62 62 CD 10_1101-2021_01_07_425675 285 15 ( ( -LRB- 10_1101-2021_01_07_425675 285 16 9 9 CD 10_1101-2021_01_07_425675 285 17 ) ) -RRB- 10_1101-2021_01_07_425675 285 18 , , , 10_1101-2021_01_07_425675 285 19 835 835 CD 10_1101-2021_01_07_425675 285 20 - - SYM 10_1101-2021_01_07_425675 285 21 839 839 CD 10_1101-2021_01_07_425675 285 22 . . . 10_1101-2021_01_07_425675 286 1 452 452 CD 10_1101-2021_01_07_425675 286 2 34 34 CD 10_1101-2021_01_07_425675 286 3 . . . 10_1101-2021_01_07_425675 287 1 Entzminger Entzminger NNP 10_1101-2021_01_07_425675 287 2 , , , 10_1101-2021_01_07_425675 287 3 K. K. NNP 10_1101-2021_01_07_425675 287 4 C. C. NNP 10_1101-2021_01_07_425675 287 5 ; ; : 10_1101-2021_01_07_425675 287 6 Hyun Hyun NNP 10_1101-2021_01_07_425675 287 7 , , , 10_1101-2021_01_07_425675 287 8 J.-m J.-m NNP 10_1101-2021_01_07_425675 287 9 . . . 10_1101-2021_01_07_425675 287 10 ; ; : 10_1101-2021_01_07_425675 287 11 Pantazes Pantazes NNP 10_1101-2021_01_07_425675 287 12 , , , 10_1101-2021_01_07_425675 287 13 R. R. NNP 10_1101-2021_01_07_425675 287 14 J. J. NNP 10_1101-2021_01_07_425675 287 15 ; ; : 10_1101-2021_01_07_425675 287 16 Patterson Patterson NNP 10_1101-2021_01_07_425675 287 17 - - HYPH 10_1101-2021_01_07_425675 287 18 Orazem Orazem NNP 10_1101-2021_01_07_425675 287 19 , , , 10_1101-2021_01_07_425675 287 20 A. A. NNP 10_1101-2021_01_07_425675 287 21 C. C. NNP 10_1101-2021_01_07_425675 287 22 ; ; : 10_1101-2021_01_07_425675 287 23 Qerqez Qerqez NNP 10_1101-2021_01_07_425675 287 24 , , , 10_1101-2021_01_07_425675 287 25 A. a. NN 10_1101-2021_01_07_425675 287 26 N. n. NN 10_1101-2021_01_07_425675 287 27 ; ; : 10_1101-2021_01_07_425675 287 28 453 453 CD 10_1101-2021_01_07_425675 287 29 Frye Frye NNP 10_1101-2021_01_07_425675 287 30 , , , 10_1101-2021_01_07_425675 287 31 Z. Z. NNP 10_1101-2021_01_07_425675 287 32 P. P. NNP 10_1101-2021_01_07_425675 287 33 ; ; : 10_1101-2021_01_07_425675 287 34 Hughes Hughes NNP 10_1101-2021_01_07_425675 287 35 , , , 10_1101-2021_01_07_425675 287 36 R. R. NNP 10_1101-2021_01_07_425675 287 37 A. a. NN 10_1101-2021_01_07_425675 287 38 ; ; : 10_1101-2021_01_07_425675 287 39 Ellington Ellington NNP 10_1101-2021_01_07_425675 287 40 , , , 10_1101-2021_01_07_425675 287 41 A. A. NNP 10_1101-2021_01_07_425675 287 42 D. D. NNP 10_1101-2021_01_07_425675 287 43 ; ; : 10_1101-2021_01_07_425675 287 44 Lieberman Lieberman NNP 10_1101-2021_01_07_425675 287 45 , , , 10_1101-2021_01_07_425675 287 46 R. R. NNP 10_1101-2021_01_07_425675 287 47 L. L. NNP 10_1101-2021_01_07_425675 287 48 ; ; : 10_1101-2021_01_07_425675 287 49 Maranas Maranas NNP 10_1101-2021_01_07_425675 287 50 , , , 10_1101-2021_01_07_425675 287 51 C. C. NNP 10_1101-2021_01_07_425675 287 52 D. D. NNP 10_1101-2021_01_07_425675 287 53 , , , 10_1101-2021_01_07_425675 287 54 De De NNP 10_1101-2021_01_07_425675 287 55 novo novo NNP 10_1101-2021_01_07_425675 287 56 design design NN 10_1101-2021_01_07_425675 287 57 of of IN 10_1101-2021_01_07_425675 287 58 454 454 CD 10_1101-2021_01_07_425675 287 59 antibody antibody NN 10_1101-2021_01_07_425675 287 60 complementarity complementarity NN 10_1101-2021_01_07_425675 287 61 determining determine VBG 10_1101-2021_01_07_425675 287 62 regions region NNS 10_1101-2021_01_07_425675 287 63 binding bind VBG 10_1101-2021_01_07_425675 287 64 a a DT 10_1101-2021_01_07_425675 287 65 FLAG FLAG NNP 10_1101-2021_01_07_425675 287 66 tetra tetra JJ 10_1101-2021_01_07_425675 287 67 - - HYPH 10_1101-2021_01_07_425675 287 68 peptide peptide JJ 10_1101-2021_01_07_425675 287 69 . . . 10_1101-2021_01_07_425675 288 1 Scientific scientific JJ 10_1101-2021_01_07_425675 288 2 reports report NNS 10_1101-2021_01_07_425675 288 3 455 455 CD 10_1101-2021_01_07_425675 288 4 2017 2017 CD 10_1101-2021_01_07_425675 288 5 , , , 10_1101-2021_01_07_425675 288 6 7 7 CD 10_1101-2021_01_07_425675 288 7 ( ( -LRB- 10_1101-2021_01_07_425675 288 8 1 1 CD 10_1101-2021_01_07_425675 288 9 ) ) -RRB- 10_1101-2021_01_07_425675 288 10 , , , 10_1101-2021_01_07_425675 288 11 1 1 CD 10_1101-2021_01_07_425675 288 12 - - SYM 10_1101-2021_01_07_425675 288 13 11 11 CD 10_1101-2021_01_07_425675 288 14 . . . 10_1101-2021_01_07_425675 289 1 456 456 CD 10_1101-2021_01_07_425675 289 2 35 35 CD 10_1101-2021_01_07_425675 289 3 . . . 10_1101-2021_01_07_425675 290 1 Ikeda ikeda NN 10_1101-2021_01_07_425675 290 2 , , , 10_1101-2021_01_07_425675 290 3 K. K. NNP 10_1101-2021_01_07_425675 290 4 ; ; : 10_1101-2021_01_07_425675 290 5 Koga Koga NNP 10_1101-2021_01_07_425675 290 6 , , , 10_1101-2021_01_07_425675 290 7 T. t. NN 10_1101-2021_01_07_425675 290 8 ; ; : 10_1101-2021_01_07_425675 290 9 Sasaki Sasaki NNP 10_1101-2021_01_07_425675 290 10 , , , 10_1101-2021_01_07_425675 290 11 F. F. NNP 10_1101-2021_01_07_425675 290 12 ; ; : 10_1101-2021_01_07_425675 290 13 Ueno Ueno NNP 10_1101-2021_01_07_425675 290 14 , , , 10_1101-2021_01_07_425675 290 15 A. a. NN 10_1101-2021_01_07_425675 290 16 ; ; : 10_1101-2021_01_07_425675 290 17 Saeki Saeki NNP 10_1101-2021_01_07_425675 290 18 , , , 10_1101-2021_01_07_425675 290 19 K. K. NNP 10_1101-2021_01_07_425675 290 20 ; ; : 10_1101-2021_01_07_425675 290 21 Okuno Okuno NNP 10_1101-2021_01_07_425675 290 22 , , , 10_1101-2021_01_07_425675 290 23 T. T. NNP 10_1101-2021_01_07_425675 290 24 ; ; : 10_1101-2021_01_07_425675 290 25 Yokomizo Yokomizo NNP 10_1101-2021_01_07_425675 290 26 , , , 10_1101-2021_01_07_425675 290 27 T. T. NNP 10_1101-2021_01_07_425675 290 28 , , , 10_1101-2021_01_07_425675 290 29 Generation Generation NNP 10_1101-2021_01_07_425675 290 30 457 457 CD 10_1101-2021_01_07_425675 290 31 and and CC 10_1101-2021_01_07_425675 290 32 characterization characterization NN 10_1101-2021_01_07_425675 290 33 of of IN 10_1101-2021_01_07_425675 290 34 a a DT 10_1101-2021_01_07_425675 290 35 human human JJ 10_1101-2021_01_07_425675 290 36 - - HYPH 10_1101-2021_01_07_425675 290 37 mouse mouse NN 10_1101-2021_01_07_425675 290 38 chimeric chimeric JJ 10_1101-2021_01_07_425675 290 39 high high JJ 10_1101-2021_01_07_425675 290 40 - - HYPH 10_1101-2021_01_07_425675 290 41 affinity affinity NN 10_1101-2021_01_07_425675 290 42 antibody antibody NN 10_1101-2021_01_07_425675 290 43 that that WDT 10_1101-2021_01_07_425675 290 44 detects detect VBZ 10_1101-2021_01_07_425675 290 45 the the DT 10_1101-2021_01_07_425675 290 46 458 458 CD 10_1101-2021_01_07_425675 290 47 DYKDDDDK DYKDDDDK NNP 10_1101-2021_01_07_425675 290 48 FLAG FLAG NNP 10_1101-2021_01_07_425675 290 49 peptide peptide NN 10_1101-2021_01_07_425675 290 50 . . . 10_1101-2021_01_07_425675 291 1 Biochemical Biochemical NNP 10_1101-2021_01_07_425675 291 2 and and CC 10_1101-2021_01_07_425675 291 3 Biophysical Biophysical NNP 10_1101-2021_01_07_425675 291 4 Research Research NNP 10_1101-2021_01_07_425675 291 5 Communications Communications NNP 10_1101-2021_01_07_425675 291 6 2017 2017 CD 10_1101-2021_01_07_425675 291 7 , , , 10_1101-2021_01_07_425675 291 8 486 486 CD 10_1101-2021_01_07_425675 291 9 459 459 CD 10_1101-2021_01_07_425675 291 10 ( ( -LRB- 10_1101-2021_01_07_425675 291 11 4 4 CD 10_1101-2021_01_07_425675 291 12 ) ) -RRB- 10_1101-2021_01_07_425675 291 13 , , , 10_1101-2021_01_07_425675 291 14 1077 1077 CD 10_1101-2021_01_07_425675 291 15 - - SYM 10_1101-2021_01_07_425675 291 16 1082 1082 CD 10_1101-2021_01_07_425675 291 17 . . . 10_1101-2021_01_07_425675 292 1 460 460 CD 10_1101-2021_01_07_425675 292 2 36 36 CD 10_1101-2021_01_07_425675 292 3 . . . 10_1101-2021_01_07_425675 293 1 Lima Lima NNP 10_1101-2021_01_07_425675 293 2 , , , 10_1101-2021_01_07_425675 293 3 W. W. NNP 10_1101-2021_01_07_425675 293 4 C. C. NNP 10_1101-2021_01_07_425675 293 5 ; ; : 10_1101-2021_01_07_425675 293 6 Gasteiger Gasteiger NNP 10_1101-2021_01_07_425675 293 7 , , , 10_1101-2021_01_07_425675 293 8 E. E. NNP 10_1101-2021_01_07_425675 293 9 ; ; : 10_1101-2021_01_07_425675 293 10 Marcatili Marcatili NNP 10_1101-2021_01_07_425675 293 11 , , , 10_1101-2021_01_07_425675 293 12 P. P. NNP 10_1101-2021_01_07_425675 293 13 ; ; : 10_1101-2021_01_07_425675 293 14 Duek Duek NNP 10_1101-2021_01_07_425675 293 15 , , , 10_1101-2021_01_07_425675 293 16 P. P. NNP 10_1101-2021_01_07_425675 293 17 ; ; : 10_1101-2021_01_07_425675 293 18 Bairoch Bairoch NNP 10_1101-2021_01_07_425675 293 19 , , , 10_1101-2021_01_07_425675 293 20 A. a. NN 10_1101-2021_01_07_425675 293 21 ; ; : 10_1101-2021_01_07_425675 293 22 Cosson Cosson NNP 10_1101-2021_01_07_425675 293 23 , , , 10_1101-2021_01_07_425675 293 24 P. P. NNP 10_1101-2021_01_07_425675 293 25 , , , 10_1101-2021_01_07_425675 293 26 The the DT 10_1101-2021_01_07_425675 293 27 ABCD ABCD NNP 10_1101-2021_01_07_425675 293 28 461 461 CD 10_1101-2021_01_07_425675 293 29 database database NN 10_1101-2021_01_07_425675 293 30 : : : 10_1101-2021_01_07_425675 293 31 a a DT 10_1101-2021_01_07_425675 293 32 repository repository NN 10_1101-2021_01_07_425675 293 33 for for IN 10_1101-2021_01_07_425675 293 34 chemically chemically RB 10_1101-2021_01_07_425675 293 35 defined define VBN 10_1101-2021_01_07_425675 293 36 antibodies antibody NNS 10_1101-2021_01_07_425675 293 37 . . . 10_1101-2021_01_07_425675 294 1 Nucleic Nucleic NNP 10_1101-2021_01_07_425675 294 2 acids acid NNS 10_1101-2021_01_07_425675 294 3 research research NN 10_1101-2021_01_07_425675 294 4 2020 2020 CD 10_1101-2021_01_07_425675 294 5 , , , 10_1101-2021_01_07_425675 294 6 48 48 CD 10_1101-2021_01_07_425675 294 7 ( ( -LRB- 10_1101-2021_01_07_425675 294 8 D1 d1 NN 10_1101-2021_01_07_425675 294 9 ) ) -RRB- 10_1101-2021_01_07_425675 294 10 , , , 10_1101-2021_01_07_425675 294 11 462 462 CD 10_1101-2021_01_07_425675 294 12 D261-D264 D261-D264 NNP 10_1101-2021_01_07_425675 294 13 . . . 10_1101-2021_01_07_425675 295 1 463 463 CD 10_1101-2021_01_07_425675 295 2 37 37 CD 10_1101-2021_01_07_425675 295 3 . . . 10_1101-2021_01_07_425675 296 1 Bondt Bondt NNP 10_1101-2021_01_07_425675 296 2 , , , 10_1101-2021_01_07_425675 296 3 A. a. NN 10_1101-2021_01_07_425675 296 4 ; ; : 10_1101-2021_01_07_425675 296 5 Hoek Hoek NNP 10_1101-2021_01_07_425675 296 6 , , , 10_1101-2021_01_07_425675 296 7 M. M. NNP 10_1101-2021_01_07_425675 296 8 ; ; : 10_1101-2021_01_07_425675 296 9 Tamara Tamara NNP 10_1101-2021_01_07_425675 296 10 , , , 10_1101-2021_01_07_425675 296 11 S. S. NNP 10_1101-2021_01_07_425675 296 12 ; ; : 10_1101-2021_01_07_425675 296 13 de de NNP 10_1101-2021_01_07_425675 296 14 Graaf Graaf NNP 10_1101-2021_01_07_425675 296 15 , , , 10_1101-2021_01_07_425675 296 16 B. B. NNP 10_1101-2021_01_07_425675 296 17 ; ; : 10_1101-2021_01_07_425675 296 18 Peng Peng NNP 10_1101-2021_01_07_425675 296 19 , , , 10_1101-2021_01_07_425675 296 20 W. W. NNP 10_1101-2021_01_07_425675 296 21 ; ; : 10_1101-2021_01_07_425675 296 22 Schulte Schulte NNP 10_1101-2021_01_07_425675 296 23 , , , 10_1101-2021_01_07_425675 296 24 D. D. NNP 10_1101-2021_01_07_425675 296 25 ; ; : 10_1101-2021_01_07_425675 296 26 den den NNP 10_1101-2021_01_07_425675 296 27 Boer Boer NNP 10_1101-2021_01_07_425675 296 28 , , , 10_1101-2021_01_07_425675 296 29 M. M. NNP 10_1101-2021_01_07_425675 296 30 A. A. NNP 10_1101-2021_01_07_425675 296 31 ; ; : 10_1101-2021_01_07_425675 296 32 464 464 CD 10_1101-2021_01_07_425675 296 33 Greisch Greisch NNP 10_1101-2021_01_07_425675 296 34 , , , 10_1101-2021_01_07_425675 296 35 J.-F. J.-F. NNP 10_1101-2021_01_07_425675 296 36 ; ; : 10_1101-2021_01_07_425675 296 37 Varkila Varkila NNP 10_1101-2021_01_07_425675 296 38 , , , 10_1101-2021_01_07_425675 296 39 M. M. NNP 10_1101-2021_01_07_425675 296 40 R. R. NNP 10_1101-2021_01_07_425675 296 41 ; ; : 10_1101-2021_01_07_425675 296 42 Snijder Snijder NNP 10_1101-2021_01_07_425675 296 43 , , , 10_1101-2021_01_07_425675 296 44 J. J. NNP 10_1101-2021_01_07_425675 296 45 , , , 10_1101-2021_01_07_425675 296 46 Human Human NNP 10_1101-2021_01_07_425675 296 47 Plasma Plasma NNP 10_1101-2021_01_07_425675 296 48 IgG1 igg1 NN 10_1101-2021_01_07_425675 296 49 Repertoires repertoire NNS 10_1101-2021_01_07_425675 296 50 are be VBP 10_1101-2021_01_07_425675 296 51 Simple simple JJ 10_1101-2021_01_07_425675 296 52 , , , 10_1101-2021_01_07_425675 296 53 Unique Unique NNP 10_1101-2021_01_07_425675 296 54 , , , 10_1101-2021_01_07_425675 296 55 465 465 CD 10_1101-2021_01_07_425675 296 56 and and CC 10_1101-2021_01_07_425675 296 57 Dynamic dynamic JJ 10_1101-2021_01_07_425675 296 58 . . . 10_1101-2021_01_07_425675 297 1 SSRN SSRN NNP 10_1101-2021_01_07_425675 297 2 2020 2020 CD 10_1101-2021_01_07_425675 297 3 . . . 10_1101-2021_01_07_425675 298 1 466 466 CD 10_1101-2021_01_07_425675 298 2 38 38 CD 10_1101-2021_01_07_425675 298 3 . . . 10_1101-2021_01_07_425675 299 1 Ehrenmann Ehrenmann NNP 10_1101-2021_01_07_425675 299 2 , , , 10_1101-2021_01_07_425675 299 3 F. F. NNP 10_1101-2021_01_07_425675 299 4 ; ; : 10_1101-2021_01_07_425675 299 5 Kaas Kaas NNP 10_1101-2021_01_07_425675 299 6 , , , 10_1101-2021_01_07_425675 299 7 Q. Q. NNP 10_1101-2021_01_07_425675 299 8 ; ; : 10_1101-2021_01_07_425675 299 9 Lefranc Lefranc NNP 10_1101-2021_01_07_425675 299 10 , , , 10_1101-2021_01_07_425675 299 11 M.-P. M.-P. NNP 10_1101-2021_01_07_425675 299 12 , , , 10_1101-2021_01_07_425675 299 13 IMGT/3Dstructure IMGT/3Dstructure NNP 10_1101-2021_01_07_425675 299 14 - - HYPH 10_1101-2021_01_07_425675 299 15 DB DB NNP 10_1101-2021_01_07_425675 299 16 and and CC 10_1101-2021_01_07_425675 299 17 467 467 CD 10_1101-2021_01_07_425675 299 18 IMGT IMGT NNS 10_1101-2021_01_07_425675 299 19 / / SYM 10_1101-2021_01_07_425675 299 20 DomainGapAlign domaingapalign NN 10_1101-2021_01_07_425675 299 21 : : : 10_1101-2021_01_07_425675 299 22 a a DT 10_1101-2021_01_07_425675 299 23 database database NN 10_1101-2021_01_07_425675 299 24 and and CC 10_1101-2021_01_07_425675 299 25 a a DT 10_1101-2021_01_07_425675 299 26 tool tool NN 10_1101-2021_01_07_425675 299 27 for for IN 10_1101-2021_01_07_425675 299 28 immunoglobulins immunoglobulin NNS 10_1101-2021_01_07_425675 299 29 or or CC 10_1101-2021_01_07_425675 299 30 antibodies antibody NNS 10_1101-2021_01_07_425675 299 31 , , , 10_1101-2021_01_07_425675 299 32 T T NNP 10_1101-2021_01_07_425675 299 33 cell cell NN 10_1101-2021_01_07_425675 299 34 468 468 CD 10_1101-2021_01_07_425675 299 35 receptors receptor NNS 10_1101-2021_01_07_425675 299 36 , , , 10_1101-2021_01_07_425675 299 37 MHC MHC NNP 10_1101-2021_01_07_425675 299 38 , , , 10_1101-2021_01_07_425675 299 39 IgSF IgSF NNP 10_1101-2021_01_07_425675 299 40 and and CC 10_1101-2021_01_07_425675 299 41 MhcSF MhcSF NNP 10_1101-2021_01_07_425675 299 42 . . . 10_1101-2021_01_07_425675 300 1 Nucleic Nucleic NNP 10_1101-2021_01_07_425675 300 2 acids acid NNS 10_1101-2021_01_07_425675 300 3 research research NN 10_1101-2021_01_07_425675 300 4 2010 2010 CD 10_1101-2021_01_07_425675 300 5 , , , 10_1101-2021_01_07_425675 300 6 38 38 CD 10_1101-2021_01_07_425675 300 7 ( ( -LRB- 10_1101-2021_01_07_425675 300 8 suppl_1 suppl_1 NN 10_1101-2021_01_07_425675 300 9 ) ) -RRB- 10_1101-2021_01_07_425675 300 10 , , , 10_1101-2021_01_07_425675 300 11 D301-D307 D301-D307 NNP 10_1101-2021_01_07_425675 300 12 . . . 10_1101-2021_01_07_425675 301 1 469 469 CD 10_1101-2021_01_07_425675 301 2 39 39 CD 10_1101-2021_01_07_425675 301 3 . . . 10_1101-2021_01_07_425675 302 1 Ehrenmann Ehrenmann NNP 10_1101-2021_01_07_425675 302 2 , , , 10_1101-2021_01_07_425675 302 3 F. F. NNP 10_1101-2021_01_07_425675 302 4 ; ; : 10_1101-2021_01_07_425675 302 5 Lefranc Lefranc NNP 10_1101-2021_01_07_425675 302 6 , , , 10_1101-2021_01_07_425675 302 7 M.-P. M.-P. NNP 10_1101-2021_01_07_425675 302 8 , , , 10_1101-2021_01_07_425675 302 9 IMGT IMGT NNP 10_1101-2021_01_07_425675 302 10 / / SYM 10_1101-2021_01_07_425675 302 11 DomainGapAlign domaingapalign NN 10_1101-2021_01_07_425675 302 12 : : : 10_1101-2021_01_07_425675 302 13 IMGT IMGT NNP 10_1101-2021_01_07_425675 302 14 standardized standardized JJ 10_1101-2021_01_07_425675 302 15 analysis analysis NN 10_1101-2021_01_07_425675 302 16 of of IN 10_1101-2021_01_07_425675 302 17 470 470 CD 10_1101-2021_01_07_425675 302 18 amino amino NN 10_1101-2021_01_07_425675 302 19 acid acid NN 10_1101-2021_01_07_425675 302 20 sequences sequence NNS 10_1101-2021_01_07_425675 302 21 of of IN 10_1101-2021_01_07_425675 302 22 variable variable JJ 10_1101-2021_01_07_425675 302 23 , , , 10_1101-2021_01_07_425675 302 24 constant constant JJ 10_1101-2021_01_07_425675 302 25 , , , 10_1101-2021_01_07_425675 302 26 and and CC 10_1101-2021_01_07_425675 302 27 groove groove NN 10_1101-2021_01_07_425675 302 28 domains domain NNS 10_1101-2021_01_07_425675 302 29 ( ( -LRB- 10_1101-2021_01_07_425675 302 30 IG IG NNP 10_1101-2021_01_07_425675 302 31 , , , 10_1101-2021_01_07_425675 302 32 TR TR NNP 10_1101-2021_01_07_425675 302 33 , , , 10_1101-2021_01_07_425675 302 34 MH MH NNP 10_1101-2021_01_07_425675 302 35 , , , 10_1101-2021_01_07_425675 302 36 IgSF IgSF NNP 10_1101-2021_01_07_425675 302 37 , , , 10_1101-2021_01_07_425675 302 38 MhSF MhSF NNP 10_1101-2021_01_07_425675 302 39 ) ) -RRB- 10_1101-2021_01_07_425675 302 40 . . . 10_1101-2021_01_07_425675 303 1 471 471 CD 10_1101-2021_01_07_425675 303 2 Cold Cold NNP 10_1101-2021_01_07_425675 303 3 Spring Spring NNP 10_1101-2021_01_07_425675 303 4 Harbor Harbor NNP 10_1101-2021_01_07_425675 303 5 Protocols Protocols NNP 10_1101-2021_01_07_425675 303 6 2011 2011 CD 10_1101-2021_01_07_425675 303 7 , , , 10_1101-2021_01_07_425675 303 8 2011 2011 CD 10_1101-2021_01_07_425675 303 9 ( ( -LRB- 10_1101-2021_01_07_425675 303 10 6 6 CD 10_1101-2021_01_07_425675 303 11 ) ) -RRB- 10_1101-2021_01_07_425675 303 12 , , , 10_1101-2021_01_07_425675 303 13 pdb pdb NN 10_1101-2021_01_07_425675 303 14 . . . 10_1101-2021_01_07_425675 304 1 prot5636 prot5636 LS 10_1101-2021_01_07_425675 304 2 . . . 10_1101-2021_01_07_425675 305 1 472 472 CD 10_1101-2021_01_07_425675 305 2 40 40 CD 10_1101-2021_01_07_425675 305 3 . . . 10_1101-2021_01_07_425675 306 1 Emsley Emsley NNP 10_1101-2021_01_07_425675 306 2 , , , 10_1101-2021_01_07_425675 306 3 P. P. NNP 10_1101-2021_01_07_425675 306 4 ; ; : 10_1101-2021_01_07_425675 306 5 Cowtan Cowtan NNP 10_1101-2021_01_07_425675 306 6 , , , 10_1101-2021_01_07_425675 306 7 K. K. NNP 10_1101-2021_01_07_425675 306 8 , , , 10_1101-2021_01_07_425675 306 9 Coot Coot NNP 10_1101-2021_01_07_425675 306 10 : : : 10_1101-2021_01_07_425675 306 11 model model NN 10_1101-2021_01_07_425675 306 12 - - HYPH 10_1101-2021_01_07_425675 306 13 building building NN 10_1101-2021_01_07_425675 306 14 tools tool NNS 10_1101-2021_01_07_425675 306 15 for for IN 10_1101-2021_01_07_425675 306 16 molecular molecular JJ 10_1101-2021_01_07_425675 306 17 graphics graphic NNS 10_1101-2021_01_07_425675 306 18 . . . 10_1101-2021_01_07_425675 307 1 Acta Acta NNP 10_1101-2021_01_07_425675 307 2 473 473 CD 10_1101-2021_01_07_425675 307 3 Crystallographica Crystallographica NNP 10_1101-2021_01_07_425675 307 4 Section Section NNP 10_1101-2021_01_07_425675 307 5 D D NNP 10_1101-2021_01_07_425675 307 6 : : : 10_1101-2021_01_07_425675 307 7 Biological biological JJ 10_1101-2021_01_07_425675 307 8 Crystallography Crystallography NNP 10_1101-2021_01_07_425675 307 9 2004 2004 CD 10_1101-2021_01_07_425675 307 10 , , , 10_1101-2021_01_07_425675 307 11 60 60 CD 10_1101-2021_01_07_425675 307 12 ( ( -LRB- 10_1101-2021_01_07_425675 307 13 12 12 CD 10_1101-2021_01_07_425675 307 14 ) ) -RRB- 10_1101-2021_01_07_425675 307 15 , , , 10_1101-2021_01_07_425675 307 16 2126 2126 CD 10_1101-2021_01_07_425675 307 17 - - SYM 10_1101-2021_01_07_425675 307 18 2132 2132 CD 10_1101-2021_01_07_425675 307 19 . . . 10_1101-2021_01_07_425675 308 1 474 474 CD 10_1101-2021_01_07_425675 308 2 41 41 CD 10_1101-2021_01_07_425675 308 3 . . . 10_1101-2021_01_07_425675 309 1 Afonine Afonine NNP 10_1101-2021_01_07_425675 309 2 , , , 10_1101-2021_01_07_425675 309 3 P. P. NNP 10_1101-2021_01_07_425675 309 4 V. V. NNP 10_1101-2021_01_07_425675 309 5 ; ; : 10_1101-2021_01_07_425675 309 6 Grosse Grosse NNP 10_1101-2021_01_07_425675 309 7 - - HYPH 10_1101-2021_01_07_425675 309 8 Kunstleve Kunstleve NNP 10_1101-2021_01_07_425675 309 9 , , , 10_1101-2021_01_07_425675 309 10 R. R. NNP 10_1101-2021_01_07_425675 309 11 W. W. NNP 10_1101-2021_01_07_425675 309 12 ; ; : 10_1101-2021_01_07_425675 309 13 Echols Echols NNP 10_1101-2021_01_07_425675 309 14 , , , 10_1101-2021_01_07_425675 309 15 N. N. NNP 10_1101-2021_01_07_425675 309 16 ; ; : 10_1101-2021_01_07_425675 309 17 Headd Headd NNP 10_1101-2021_01_07_425675 309 18 , , , 10_1101-2021_01_07_425675 309 19 J. J. NNP 10_1101-2021_01_07_425675 309 20 J. J. NNP 10_1101-2021_01_07_425675 309 21 ; ; : 10_1101-2021_01_07_425675 309 22 Moriarty Moriarty NNP 10_1101-2021_01_07_425675 309 23 , , , 10_1101-2021_01_07_425675 309 24 N. N. NNP 10_1101-2021_01_07_425675 309 25 W. W. NNP 10_1101-2021_01_07_425675 309 26 ; ; : 10_1101-2021_01_07_425675 309 27 475 475 CD 10_1101-2021_01_07_425675 309 28 Mustyakimov Mustyakimov NNP 10_1101-2021_01_07_425675 309 29 , , , 10_1101-2021_01_07_425675 309 30 M. M. NNP 10_1101-2021_01_07_425675 309 31 ; ; : 10_1101-2021_01_07_425675 309 32 Terwilliger Terwilliger NNP 10_1101-2021_01_07_425675 309 33 , , , 10_1101-2021_01_07_425675 309 34 T. T. NNP 10_1101-2021_01_07_425675 309 35 C. C. NNP 10_1101-2021_01_07_425675 309 36 ; ; : 10_1101-2021_01_07_425675 309 37 Urzhumtsev Urzhumtsev NNP 10_1101-2021_01_07_425675 309 38 , , , 10_1101-2021_01_07_425675 309 39 A. a. NN 10_1101-2021_01_07_425675 309 40 ; ; : 10_1101-2021_01_07_425675 309 41 Zwart Zwart NNP 10_1101-2021_01_07_425675 309 42 , , , 10_1101-2021_01_07_425675 309 43 P. P. NNP 10_1101-2021_01_07_425675 309 44 H. H. NNP 10_1101-2021_01_07_425675 309 45 ; ; : 10_1101-2021_01_07_425675 309 46 Adams Adams NNP 10_1101-2021_01_07_425675 309 47 , , , 10_1101-2021_01_07_425675 309 48 P. P. NNP 10_1101-2021_01_07_425675 309 49 D. D. NNP 10_1101-2021_01_07_425675 309 50 , , , 10_1101-2021_01_07_425675 309 51 Towards towards IN 10_1101-2021_01_07_425675 309 52 476 476 CD 10_1101-2021_01_07_425675 309 53 automated automate VBN 10_1101-2021_01_07_425675 309 54 crystallographic crystallographic JJ 10_1101-2021_01_07_425675 309 55 structure structure NN 10_1101-2021_01_07_425675 309 56 refinement refinement NN 10_1101-2021_01_07_425675 309 57 with with IN 10_1101-2021_01_07_425675 309 58 phenix phenix NNP 10_1101-2021_01_07_425675 309 59 . . . 10_1101-2021_01_07_425675 310 1 refine refine VB 10_1101-2021_01_07_425675 310 2 . . . 10_1101-2021_01_07_425675 311 1 Acta Acta NNP 10_1101-2021_01_07_425675 311 2 Crystallographica Crystallographica NNP 10_1101-2021_01_07_425675 311 3 477 477 CD 10_1101-2021_01_07_425675 311 4 Section section NN 10_1101-2021_01_07_425675 311 5 D d NN 10_1101-2021_01_07_425675 311 6 : : : 10_1101-2021_01_07_425675 311 7 Biological Biological NNP 10_1101-2021_01_07_425675 311 8 Crystallography Crystallography NNP 10_1101-2021_01_07_425675 311 9 2012 2012 CD 10_1101-2021_01_07_425675 311 10 , , , 10_1101-2021_01_07_425675 311 11 68 68 CD 10_1101-2021_01_07_425675 311 12 ( ( -LRB- 10_1101-2021_01_07_425675 311 13 4 4 CD 10_1101-2021_01_07_425675 311 14 ) ) -RRB- 10_1101-2021_01_07_425675 311 15 , , , 10_1101-2021_01_07_425675 311 16 352 352 CD 10_1101-2021_01_07_425675 311 17 - - SYM 10_1101-2021_01_07_425675 311 18 367 367 CD 10_1101-2021_01_07_425675 311 19 . . . 10_1101-2021_01_07_425675 312 1 478 478 CD 10_1101-2021_01_07_425675 312 2 42 42 CD 10_1101-2021_01_07_425675 312 3 . . . 10_1101-2021_01_07_425675 313 1 Chen Chen NNP 10_1101-2021_01_07_425675 313 2 , , , 10_1101-2021_01_07_425675 313 3 V. V. NNP 10_1101-2021_01_07_425675 313 4 B. B. NNP 10_1101-2021_01_07_425675 313 5 ; ; : 10_1101-2021_01_07_425675 313 6 Arendall Arendall NNP 10_1101-2021_01_07_425675 313 7 , , , 10_1101-2021_01_07_425675 313 8 W. W. NNP 10_1101-2021_01_07_425675 313 9 B. B. NNP 10_1101-2021_01_07_425675 313 10 ; ; : 10_1101-2021_01_07_425675 313 11 Headd Headd NNP 10_1101-2021_01_07_425675 313 12 , , , 10_1101-2021_01_07_425675 313 13 J. J. NNP 10_1101-2021_01_07_425675 313 14 J. J. NNP 10_1101-2021_01_07_425675 313 15 ; ; : 10_1101-2021_01_07_425675 313 16 Keedy Keedy NNP 10_1101-2021_01_07_425675 313 17 , , , 10_1101-2021_01_07_425675 313 18 D. D. NNP 10_1101-2021_01_07_425675 313 19 A. a. NN 10_1101-2021_01_07_425675 313 20 ; ; : 10_1101-2021_01_07_425675 313 21 Immormino Immormino NNP 10_1101-2021_01_07_425675 313 22 , , , 10_1101-2021_01_07_425675 313 23 R. R. NNP 10_1101-2021_01_07_425675 313 24 M. M. NNP 10_1101-2021_01_07_425675 313 25 ; ; : 10_1101-2021_01_07_425675 313 26 Kapral Kapral NNP 10_1101-2021_01_07_425675 313 27 , , , 10_1101-2021_01_07_425675 313 28 G. G. NNP 10_1101-2021_01_07_425675 313 29 479 479 CD 10_1101-2021_01_07_425675 313 30 J. J. NNP 10_1101-2021_01_07_425675 313 31 ; ; : 10_1101-2021_01_07_425675 313 32 Murray Murray NNP 10_1101-2021_01_07_425675 313 33 , , , 10_1101-2021_01_07_425675 313 34 L. L. NNP 10_1101-2021_01_07_425675 313 35 W. W. NNP 10_1101-2021_01_07_425675 313 36 ; ; : 10_1101-2021_01_07_425675 313 37 Richardson Richardson NNP 10_1101-2021_01_07_425675 313 38 , , , 10_1101-2021_01_07_425675 313 39 J. J. NNP 10_1101-2021_01_07_425675 313 40 S. S. NNP 10_1101-2021_01_07_425675 313 41 ; ; : 10_1101-2021_01_07_425675 313 42 Richardson Richardson NNP 10_1101-2021_01_07_425675 313 43 , , , 10_1101-2021_01_07_425675 313 44 D. D. NNP 10_1101-2021_01_07_425675 313 45 C. C. NNP 10_1101-2021_01_07_425675 313 46 , , , 10_1101-2021_01_07_425675 313 47 MolProbity MolProbity NNP 10_1101-2021_01_07_425675 313 48 : : : 10_1101-2021_01_07_425675 313 49 all all DT 10_1101-2021_01_07_425675 313 50 - - HYPH 10_1101-2021_01_07_425675 313 51 atom atom NN 10_1101-2021_01_07_425675 313 52 structure structure NN 10_1101-2021_01_07_425675 313 53 validation validation NN 10_1101-2021_01_07_425675 313 54 480 480 CD 10_1101-2021_01_07_425675 313 55 for for IN 10_1101-2021_01_07_425675 313 56 macromolecular macromolecular NN 10_1101-2021_01_07_425675 313 57 crystallography crystallography NN 10_1101-2021_01_07_425675 313 58 . . . 10_1101-2021_01_07_425675 314 1 Acta Acta NNP 10_1101-2021_01_07_425675 314 2 Crystallographica Crystallographica NNP 10_1101-2021_01_07_425675 314 3 Section Section NNP 10_1101-2021_01_07_425675 314 4 D D NNP 10_1101-2021_01_07_425675 314 5 : : : 10_1101-2021_01_07_425675 314 6 Biological Biological NNP 10_1101-2021_01_07_425675 314 7 481 481 CD 10_1101-2021_01_07_425675 314 8 Crystallography Crystallography NNP 10_1101-2021_01_07_425675 314 9 2010 2010 CD 10_1101-2021_01_07_425675 314 10 , , , 10_1101-2021_01_07_425675 314 11 66 66 CD 10_1101-2021_01_07_425675 314 12 ( ( -LRB- 10_1101-2021_01_07_425675 314 13 1 1 CD 10_1101-2021_01_07_425675 314 14 ) ) -RRB- 10_1101-2021_01_07_425675 314 15 , , , 10_1101-2021_01_07_425675 314 16 12 12 CD 10_1101-2021_01_07_425675 314 17 - - SYM 10_1101-2021_01_07_425675 314 18 21 21 CD 10_1101-2021_01_07_425675 314 19 . . . 10_1101-2021_01_07_425675 315 1 482 482 CD 10_1101-2021_01_07_425675 315 2 43 43 CD 10_1101-2021_01_07_425675 315 3 . . . 10_1101-2021_01_07_425675 316 1 Fuglsang Fuglsang NNP 10_1101-2021_01_07_425675 316 2 , , , 10_1101-2021_01_07_425675 316 3 A. A. NNP 10_1101-2021_01_07_425675 316 4 , , , 10_1101-2021_01_07_425675 316 5 Codon Codon NNP 10_1101-2021_01_07_425675 316 6 optimizer optimizer NN 10_1101-2021_01_07_425675 316 7 : : : 10_1101-2021_01_07_425675 316 8 a a DT 10_1101-2021_01_07_425675 316 9 freeware freeware JJ 10_1101-2021_01_07_425675 316 10 tool tool NN 10_1101-2021_01_07_425675 316 11 for for IN 10_1101-2021_01_07_425675 316 12 codon codon NNP 10_1101-2021_01_07_425675 316 13 optimization optimization NN 10_1101-2021_01_07_425675 316 14 . . . 10_1101-2021_01_07_425675 317 1 Protein protein NN 10_1101-2021_01_07_425675 317 2 483 483 CD 10_1101-2021_01_07_425675 317 3 expression expression NN 10_1101-2021_01_07_425675 317 4 and and CC 10_1101-2021_01_07_425675 317 5 purification purification NN 10_1101-2021_01_07_425675 317 6 2003 2003 CD 10_1101-2021_01_07_425675 317 7 , , , 10_1101-2021_01_07_425675 317 8 31 31 CD 10_1101-2021_01_07_425675 317 9 ( ( -LRB- 10_1101-2021_01_07_425675 317 10 2 2 CD 10_1101-2021_01_07_425675 317 11 ) ) -RRB- 10_1101-2021_01_07_425675 317 12 , , , 10_1101-2021_01_07_425675 317 13 247 247 CD 10_1101-2021_01_07_425675 317 14 - - SYM 10_1101-2021_01_07_425675 317 15 249 249 CD 10_1101-2021_01_07_425675 317 16 . . . 10_1101-2021_01_07_425675 318 1 484 484 CD 10_1101-2021_01_07_425675 318 2 44 44 CD 10_1101-2021_01_07_425675 318 3 . . . 10_1101-2021_01_07_425675 319 1 García García NNP 10_1101-2021_01_07_425675 319 2 - - HYPH 10_1101-2021_01_07_425675 319 3 Nafría Nafría NNP 10_1101-2021_01_07_425675 319 4 , , , 10_1101-2021_01_07_425675 319 5 J. J. NNP 10_1101-2021_01_07_425675 319 6 ; ; : 10_1101-2021_01_07_425675 319 7 Watson Watson NNP 10_1101-2021_01_07_425675 319 8 , , , 10_1101-2021_01_07_425675 319 9 J. J. NNP 10_1101-2021_01_07_425675 319 10 F. F. NNP 10_1101-2021_01_07_425675 319 11 ; ; : 10_1101-2021_01_07_425675 319 12 Greger Greger NNP 10_1101-2021_01_07_425675 319 13 , , , 10_1101-2021_01_07_425675 319 14 I. I. NNP 10_1101-2021_01_07_425675 319 15 H. H. NNP 10_1101-2021_01_07_425675 319 16 , , , 10_1101-2021_01_07_425675 319 17 IVA IVA NNP 10_1101-2021_01_07_425675 319 18 cloning clone VBG 10_1101-2021_01_07_425675 319 19 : : : 10_1101-2021_01_07_425675 319 20 a a DT 10_1101-2021_01_07_425675 319 21 single single JJ 10_1101-2021_01_07_425675 319 22 - - HYPH 10_1101-2021_01_07_425675 319 23 tube tube NN 10_1101-2021_01_07_425675 319 24 universal universal NNP 10_1101-2021_01_07_425675 319 25 485 485 CD 10_1101-2021_01_07_425675 319 26 cloning clone VBG 10_1101-2021_01_07_425675 319 27 system system NN 10_1101-2021_01_07_425675 319 28 exploiting exploit VBG 10_1101-2021_01_07_425675 319 29 bacterial bacterial JJ 10_1101-2021_01_07_425675 319 30 in in IN 10_1101-2021_01_07_425675 319 31 vivo vivo NNP 10_1101-2021_01_07_425675 319 32 assembly assembly NNP 10_1101-2021_01_07_425675 319 33 . . . 10_1101-2021_01_07_425675 320 1 Scientific scientific JJ 10_1101-2021_01_07_425675 320 2 reports report NNS 10_1101-2021_01_07_425675 320 3 2016 2016 CD 10_1101-2021_01_07_425675 320 4 , , , 10_1101-2021_01_07_425675 320 5 6 6 CD 10_1101-2021_01_07_425675 320 6 , , , 10_1101-2021_01_07_425675 320 7 27459 27459 CD 10_1101-2021_01_07_425675 320 8 . . . 10_1101-2021_01_07_425675 321 1 486 486 CD 10_1101-2021_01_07_425675 321 2 487 487 CD 10_1101-2021_01_07_425675 321 3 488 488 CD 10_1101-2021_01_07_425675 321 4 .CC .CC : 10_1101-2021_01_07_425675 321 5 - - : 10_1101-2021_01_07_425675 321 6 BY by IN 10_1101-2021_01_07_425675 321 7 4.0 4.0 CD 10_1101-2021_01_07_425675 321 8 International International NNP 10_1101-2021_01_07_425675 321 9 licenseavailable licenseavailable NN 10_1101-2021_01_07_425675 321 10 under under IN 10_1101-2021_01_07_425675 321 11 a a DT 10_1101-2021_01_07_425675 321 12 ( ( -LRB- 10_1101-2021_01_07_425675 321 13 which which WDT 10_1101-2021_01_07_425675 321 14 was be VBD 10_1101-2021_01_07_425675 321 15 not not RB 10_1101-2021_01_07_425675 321 16 certified certify VBN 10_1101-2021_01_07_425675 321 17 by by IN 10_1101-2021_01_07_425675 321 18 peer peer NN 10_1101-2021_01_07_425675 321 19 review review NN 10_1101-2021_01_07_425675 321 20 ) ) -RRB- 10_1101-2021_01_07_425675 321 21 is be VBZ 10_1101-2021_01_07_425675 321 22 the the DT 10_1101-2021_01_07_425675 321 23 author author NN 10_1101-2021_01_07_425675 321 24 / / SYM 10_1101-2021_01_07_425675 321 25 funder funder NN 10_1101-2021_01_07_425675 321 26 , , , 10_1101-2021_01_07_425675 321 27 who who WP 10_1101-2021_01_07_425675 321 28 has have VBZ 10_1101-2021_01_07_425675 321 29 granted grant VBN 10_1101-2021_01_07_425675 321 30 bioRxiv biorxiv IN 10_1101-2021_01_07_425675 321 31 a a DT 10_1101-2021_01_07_425675 321 32 license license NN 10_1101-2021_01_07_425675 321 33 to to TO 10_1101-2021_01_07_425675 321 34 display display VB 10_1101-2021_01_07_425675 321 35 the the DT 10_1101-2021_01_07_425675 321 36 preprint preprint NN 10_1101-2021_01_07_425675 321 37 in in IN 10_1101-2021_01_07_425675 321 38 perpetuity perpetuity NN 10_1101-2021_01_07_425675 321 39 . . . 10_1101-2021_01_07_425675 322 1 It -PRON- PRP 10_1101-2021_01_07_425675 322 2 is be VBZ 10_1101-2021_01_07_425675 322 3 made make VBN 10_1101-2021_01_07_425675 322 4 The the DT 10_1101-2021_01_07_425675 322 5 copyright copyright NN 10_1101-2021_01_07_425675 322 6 holder holder NN 10_1101-2021_01_07_425675 322 7 for for IN 10_1101-2021_01_07_425675 322 8 this this DT 10_1101-2021_01_07_425675 322 9 preprintthis preprintthis NN 10_1101-2021_01_07_425675 322 10 version version NN 10_1101-2021_01_07_425675 322 11 posted post VBD 10_1101-2021_01_07_425675 322 12 January January NNP 10_1101-2021_01_07_425675 322 13 8 8 CD 10_1101-2021_01_07_425675 322 14 , , , 10_1101-2021_01_07_425675 322 15 2021 2021 CD 10_1101-2021_01_07_425675 322 16 . . . 10_1101-2021_01_07_425675 322 17 ; ; : 10_1101-2021_01_07_425675 322 18 https://doi.org/10.1101/2021.01.07.425675doi https://doi.org/10.1101/2021.01.07.425675doi NN 10_1101-2021_01_07_425675 322 19 : : : 10_1101-2021_01_07_425675 322 20 bioRxiv biorxiv VB 10_1101-2021_01_07_425675 322 21 preprint preprint NN 10_1101-2021_01_07_425675 322 22 https://doi.org/10.1101/2021.01.07.425675 https://doi.org/10.1101/2021.01.07.425675 NN 10_1101-2021_01_07_425675 322 23 http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/ ADD