# pos

id: cord-316033-xg8eb2nm
pos: NNP
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lemma:
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# ent

id: cord-000556-uu1oz2ei
type: DNA
entity:
  FMN riboswitches gcvB glycine intron_gpII lysine alpha_RBS LR PK1 isrK MOCORNA RNaseP_bact_a tmRNA and 6S sRNAs


id: cord-000556-uu1oz2ei
type: PROTEIN
entity:
  phospholipid synthesis protein ribosomal protein S2 aconitate hydratase 2 peptide chain release factor 2


id: cord-000012-p56v8wi1
type: CHEMICAL
entity:
  N R Project in Bioinformatics Modulome the Ministère de l Education Nationale de YB is the leader of


id: cord-018804-wj35q88f
type: DISEASE
entity:
  influenza in birds or hantavirus in rodents The same happens in the laboratory where viruses are usually cultivated during years in the same cellular type In


id: cord-018437-yjvwa1ot
type: PROTEIN
entity:
  glycoprotein S membrane glycoprotein M nucleocapsid phosphoprotein N hemagglutinin esterase glycoprotein HE and envelope protein E


id: cord-018437-yjvwa1ot
type: GGP
entity:
  proteins spike glycoprotein S membrane glycoprotein M nucleocapsid phosphoprotein N hemagglutinin esterase glycoprotein HE and envelope protein E


id: cord-014461-2ubh9u8r
type: DNA
entity:
  78 Aerococcus viridans LL1 sequence accession AJTG00000000 79 Bacillus anthracis H9401 sequence accession


id: cord-014461-2ubh9u8r
type: DNA
entity:
  CP002093 1 plasmid pXO2 80 Bacillus atrophaeus C89 sequence accession AJRJ00000000 81 Bacillus cereus NC7401 sequence accession AP007209 chromosome


id: cord-014461-2ubh9u8r
type: PROTEIN
entity:
  CAJL01000030 107 Staphylococcus hominis ZBW5 sequence accession AKGC00000000 108 Staphylococcus saprophyticus subsp saprophyticus M1 1 sequence accession AHKB00000000 109 Streptococcus mutans GS 5 sequence accession CP003686 110 Streptococcus pyogenes M1 476 sequence accession AP012491 111 Streptococcus salivarius PS4 sequence accession AJFW00000000 112 Streptococcus thermophilus Strain MN ZLW 002 sequence


id: cord-014461-2ubh9u8r
type: DNA
entity:
  Smilax china sequence accession NC_015104 206 Elodea canadensis sequence accession JQ310743 207 Ogura type mitochondrial genome sequence


id: cord-014461-2ubh9u8r
type: DNA
entity:
  AJMJ00000000 210 Animal genomes Helicoverpa armigera sequence accession HQ613271 211 Plasmids plasmidIncN plasmid pRSB201 sequence accession JN102341 212 plasmidIncN plasmid pRSB203 sequence accession JN102342 212 plasmidIncN plasmid pRSB205 sequence accession JN102343 212 plasmidIncN plasmid pRSB206 sequence accession JN102344 212 Complete Genome Sequence


id: cord-014461-2ubh9u8r
type: DNA
entity:
  Hyperthermophilic Cellulolytic Crenarchaeon Thermogladius cellulolyticus 1633 Complete Genome Sequence


id: cord-265329-bsypo08l
type: DNA
entity:
  sixth 1899 1923 and seventh El Tor cholera pandemic 1961 1962 1963 1964 1965 1966 1967 1968 1969 1970 1971 1972 1973 1974 1975


id: cord-017932-vmtjc8ct
type: GGP
entity:
  Borrelia Clostridium Escherichia coli Salmonella Streptococcus pneumonia Ureaplasma Coccidioides Penicillium


id: cord-304607-td0776wj
type: CHEMICAL
entity:
  Saccharomyces cerevisiae Goffeau et al 1996 and Caenorhabditis elegans the C elegans Sequencing Consortium 1998


id: cord-016798-tv2ntug6
type: TAXON
entity:
  syncytial virus bovine adenovirus bovine rhinovirus bovine coronavirus bovine reovirus bovine enterovirus


id: cord-003316-r5te5xob
type: DNA
entity:
  core genome accessory genome housekeeping genes MLST genotypic markers plasmid sequence virulence factors


id: cord-277687-u3q36o3e
type: DISEASE
entity:
  human immunodeficiency virus human parainfluenza virus 1 4 human metapneumovirus human coronaviruses 229E OC43 NL63 HKU1 SARS MERS


id: cord-348515-bqqyly23
type: PROTEIN
entity:
  AB330088_Gomen_1952_7p JN860679_JPN_Takeuchi_317_1958 AF065067_USA_55142_vaccine_1962_7a AY594256_USA_vaccine_1962


id: cord-348515-bqqyly23
type: GGP
entity:
  AF065067_USA_55142_vaccine_1962_7a AY594256_USA_vaccine_1962 AF515814_CHN_Beijing AY495969_CHN_vaccine JN860676_AR_87 922_1987_7h AF053086_JPN_383_1992_7d AF053087_JPN_bal_1995_7d2 AY769945_KR_95 81_1995_7d


id: cord-320005-i30t7cvr
type: LAW
entity:
  Article 1 of this universal declaration on the human genome and human rights states The human genome


id: cord-302047-vv5gpldi
type: DNA
entity:
  2019 11 14 journal Virus Evol DOI 10 1093 ve vez045 sha f6e985e472df7bba7a7ef1568336c0443b919639 doc_id 302047 cord_uid vv5gpldi Viruses


id: cord-302047-vv5gpldi
type: DNA
entity:
  Human Adenovirus Type 5 Recombinant Rabies Glycoprotein Vaccine ONRAB Vaccine Reverse Genetics System Demonstrates That Rotavirus Nonstructural Protein NSP6


id: cord-302047-vv5gpldi
type: DNA
entity:
  Refactored Phage Genome Chimpanzee Adenovirus Vaccine Generates Acute and Durable Protective Immunity Against Ebolavirus Challenge Novel Defective Interfering DNAs


id: cord-302047-vv5gpldi
type: ORG
entity:
  a Nonprogressing Mother and Child Poxviral Promoters for Improving the Immunogenicity of MVA Delivered Vaccines


id: cord-302047-vv5gpldi
type: WORK_OF_ART
entity:
  Genome Specific Targeting to CD4þ Cells of Recombinant Vesicular Stomatitis Viruses Encoding Human Immunodeficiency Virus Envelope Proteins BSMV Genome Mediated Expression of a Foreign Gene in Dicot and


id: cord-302047-vv5gpldi
type: LOC
entity:
  Trans acting Genes or Elements Instability and Reiteration of DNA Sequences Within the Vaccinia Virus Genome


id: cord-302047-vv5gpldi
type: ORG
entity:
  the HIV 1 Group M Subtypes Deletion and Recombination Events Between the DNA A and DNA B Components of Indian Cassava infecting Geminiviruses Generate Defective Molecules


id: cord-302047-vv5gpldi
type: WORK_OF_ART
entity:
  RNA Genome of Vesicular Stomatitis Virus Positional Effects on Stability of Expression Predicting the Stability of Homologous Gene Duplications


id: cord-302047-vv5gpldi
type: WORK_OF_ART
entity:
  the Bacteriophage X174 Advancement and Applications of Peptide Phage Display Technology in Biomedical Science Construction


id: cord-015850-ef6svn8f
type: DNA
entity:
  rRNA 4 Genome size kb Animals Homo sapiens human 16 5 Takifugu rubripes Torafugu fi sh 16 representative animal species mitochondrial DNA genomes


id: cord-015850-ef6svn8f
type: CELL_LINE
entity:
  diploid DD cultivated species T durum and tetraploid AABB wild species Aegilops tauschii 75 A genome duplication


id: cord-346335-el45v0a5
type: ORG
entity:
  National Center for Biotechnology Information A Maximum Entropy Principle for the Distribution of Local Complexity in Naturally Occurring Nucleotide Sequences Fractals


id: cord-022128-r8el8nqm
type: CHEBI
entity:
  amino acid substitution 2 6 Evolutionary origins evolvability and consequences of high mutation rates fidelity mutants 2 7 Hypermutagenesis and its application to generating a variation APOBEC and ADAR


id: cord-022128-r8el8nqm
type: DISEASE
entity:
  influenza A H1N1 pandemic virus The Phylogenetic Handbook A Practical Approach to DNA and Protein Phylogeny The role of the APOBEC3 family


id: cord-304498-ty41xob0
type: DISEASE
entity:
  coronavirus transcription Coronavirus transcription subgenomic mouse hepatitis virus replicative intermediates function


id: cord-318392-r9bbomvk
type: DNA
entity:
  ORF1a n 28 ORF1b n 19 32 kDa non structural protein NSP gene n 6 hemagglutinin esterase HE gene n 2 S gene n 18 4 9 kDa NSP gene n 2 4 8 kDa NSP gene


id: cord-318392-r9bbomvk
type: ORG
entity:
  the International Committee on Taxonomy of Viruses International Union of Microbiological Societies Virology Division Comparative


id: cord-334394-qgyzk7th
type: DNA
entity:
  Deltaviruses PmacDV SRR7910143 MmonDV SRR2136906 OvirDV SRR4256033 TgutDV SRR5001850 and IchiDV SRR8954566


id: cord-016293-pyb00pt5
type: GGP
entity:
  Alzheimer s disease Parkinson s disease heart disease and kidney failure Likewise scientists regard these


id: cord-022262-ck2lhojz
type: GGP
entity:
  CD155 5 Coxsackieviruses 1 11 13 15 17 18 19 20 21 22 24 Common cold infantile diarrhea ICAM lt The following


# url

id: cord-316033-xg8eb2nm
domain: s3.amazonaws.com
url:
  http://s3.amazonaws.com/proj-bip-prod-publicread/hisomics/ALv5/Genome_Assembly/Genome_assemblies.tar.gz


id: cord-316033-xg8eb2nm
domain: s3.amazonaws.com
url:
  http://s3.amazonaws.com/projbip-prod-publicread/his-omics/ALv5/Genome_Assembly/AL-version2-genome-assembly.fasta.gz


id: cord-316033-xg8eb2nm
domain: s3.amazonaws.com
url:
  http://s3.amazonaws.com/proj-bip-prod-publicread/his-omics/ALv5/Genome_Assembly/AL-ver-sion3-genome-assembly.fasta.gz


id: cord-316033-xg8eb2nm
domain: s3.amazonaws.com
url:
  http://s3.amazonaws.com/proj-bip-prod-publicread/hisomics/ALv5/Genome_Assembly/AL-version4-genome-assembly.fasta.gz


id: cord-316033-xg8eb2nm
domain: s3.amazonaws.com
url:
  http://s3.amazonaws.com/proj-bip-prod-publicread/his-omics/ALv5/Genome_Assembly/AL-version5-genomeassembly.fasta.gz


# bib

id: cord-000012-p56v8wi1
title: Molecular evidence for the evolution of ichnoviruses from ascoviruses by symbiogenesis
author: Bigot, Yves
date: 2008-09-18
txt: ./txt/cord-000012-p56v8wi1.txt
cache: ./cache/cord-000012-p56v8wi1.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567993/
doi: 10.1186/1471-2148-8-253
summary:
  CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. With respect to both species number and mechanisms that lead to successful parasitism, endoparasitic wasps are known to inject secretions at oviposition, but only a few lineages use viruses or virus-like particles (VLPs) to evade or to suppress host defences. Extending our investigations to proteins encoded by open reading frames of certain ascoviruses and bracoviruses, hosts and bacteria, in the light of recent analyses about the involvement of the replication machinery of virus groups related to ascoviruses in lateral gene transfer [29] , we discuss the robustness and the limits of the molecular evidence supporting an ascovirus origin for ichnovirus lineages.

abstract:
  BACKGROUND: Female endoparasitic ichneumonid wasps inject virus-like particles into their caterpillar hosts to suppress immunity. These particles are classified as ichnovirus virions and resemble ascovirus virions, which are also transmitted by parasitic wasps and attack caterpillars. Ascoviruses replicate DNA and produce virions. Polydnavirus DNA consists of wasp DNA replicated by the wasp from its genome, which also directs particle synthesis. Structural similarities between ascovirus and ichnovirus particles and the biology of their transmission suggest that ichnoviruses evolved from ascoviruses, although molecular evidence for this hypothesis is lacking. RESULTS: Here we show that a family of unique pox-D5 NTPase proteins in the Glypta fumiferanae ichnovirus are related to three Diadromus pulchellus ascovirus proteins encoded by ORFs 90, 91 and 93. A new alignment technique also shows that two proteins from a related ichnovirus are orthologs of other ascovirus virion proteins. CONCLUSION: Our results provide molecular evidence supporting the origin of ichnoviruses from ascoviruses by lateral transfer of ascoviral genes into ichneumonid wasp genomes, perhaps the first example of symbiogenesis between large DNA viruses and eukaryotic organisms. We also discuss the limits of this evidence through complementary studies, which revealed that passive lateral transfer of viral genes among polydnaviral, bacterial, and wasp genomes may have occurred repeatedly through an intimate coupling of both recombination and replication of viral genomes during evolution. The impact of passive lateral transfers on evolutionary relationships between polydnaviruses and viruses with large double-stranded genomes is considered in the context of the theory of symbiogenesis.


id: cord-000556-uu1oz2ei
title: RNA-Seq Based Transcriptional Map of Bovine Respiratory Disease Pathogen “Histophilus somni 2336”
author: Kumar, Ranjit
date: 2012-01-20
txt: ./txt/cord-000556-uu1oz2ei.txt
cache: ./cache/cord-000556-uu1oz2ei.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3262788/
doi: 10.1371/journal.pone.0029435
summary:
  Whole genome transcriptome analysis is a complementary method to identify "novel" genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. Therefore, genome structural annotation or the identification and demarcation of boundaries of functional elements in a genome (e.g., genes, non-coding RNAs, proteins, and regulatory elements) are critical elements in infectious disease systems biology. Whole genome transcriptome studies (such as whole genome tiling arrays [13, 14, 15] and high throughput sequencing [16, 17] ) are complementary experimental approaches for bacterial genome annotation and can identify ''''novel'''' genes, gene boundaries, regulatory regions, intergenic regions, and operon structures. We compared the RNA-Seq based transcriptome map with the available genome annotation to identify expressed, novel, and intergenic regions in the genome. The single nucleotide resolution map helped uncover the structure and complexity of this pathogen''s transcriptome and led to the identification of novel, small RNAs and protein coding genes as well as gene co-expression.

abstract:
  Genome structural annotation, i.e., identification and demarcation of the boundaries for all the functional elements in a genome (e.g., genes, non-coding RNAs, proteins and regulatory elements), is a prerequisite for systems level analysis. Current genome annotation programs do not identify all of the functional elements of the genome, especially small non-coding RNAs (sRNAs). Whole genome transcriptome analysis is a complementary method to identify “novel” genes, small RNAs, regulatory regions, and operon structures, thus improving the structural annotation in bacteria. In particular, the identification of non-coding RNAs has revealed their widespread occurrence and functional importance in gene regulation, stress and virulence. However, very little is known about non-coding transcripts in Histophilus somni, one of the causative agents of Bovine Respiratory Disease (BRD) as well as bovine infertility, abortion, septicemia, arthritis, myocarditis, and thrombotic meningoencephalitis. In this study, we report a single nucleotide resolution transcriptome map of H. somni strain 2336 using RNA-Seq method. The RNA-Seq based transcriptome map identified 94 sRNAs in the H. somni genome of which 82 sRNAs were never predicted or reported in earlier studies. We also identified 38 novel potential protein coding open reading frames that were absent in the current genome annotation. The transcriptome map allowed the identification of 278 operon (total 730 genes) structures in the genome. When compared with the genome sequence of a non-virulent strain 129Pt, a disproportionate number of sRNAs (∼30%) were located in genomic region unique to strain 2336 (∼18% of the total genome). This observation suggests that a number of the newly identified sRNAs in strain 2336 may be involved in strain-specific adaptations.


id: cord-000902-ew8orn0z
title: Coevolution between simple sequence repeats (SSRs) and virus genome size
author: Zhao, Xiangyan
date: 2012-08-30
txt: ./txt/cord-000902-ew8orn0z.txt
cache: ./cache/cord-000902-ew8orn0z.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3585866/
doi: 10.1186/1471-2164-13-435
summary:
  The results showed that simple sequence repeats (SSRs) is strongly, positively and significantly correlated with genome size. While, relative abundance and relative density were examined to make the SSRs comparison parallel among differently sized species genomes; principal component analysis (PCA) was designed to investigate which repeat class(es) made a greater contribution to the variance among virus species as well as the relationships between repeat classes. Therefore, the 257 genome sequences were selected as samples for the analysis of relationship between SSRs distribution and genome size in the level of the whole virus. We surveyed the distribution of different SSR classes in virus genomes to investigate the relationship between repeat classes (mono-, di-, tri-, tetra-, penta-and hexa-) and genome sequence length. Coevolution between simple sequence repeats (SSRs) and virus genome size

abstract:
  BACKGROUND: Relationship between the level of repetitiveness in genomic sequence and genome size has been investigated by making use of complete prokaryotic and eukaryotic genomes, but relevant studies have been rarely made in virus genomes. RESULTS: In this study, a total of 257 viruses were examined, which cover 90% of genera. The results showed that simple sequence repeats (SSRs) is strongly, positively and significantly correlated with genome size. Certain repeat class is distributed in a certain range of genome sequence length. Mono-, di- and tri- repeats are widely distributed in all virus genomes, tetra- SSRs as a common component consist in genomes which more than 100 kb in size; in the range of genome < 100 kb, genomes containing penta- and hexa- SSRs are not more than 50%. Principal components analysis (PCA) indicated that dinucleotide repeat affects the differences of SSRs most strongly among virus genomes. Results showed that SSRs tend to accumulate in larger virus genomes; and the longer genome sequence, the longer repeat units. CONCLUSIONS: We conducted this research standing on the height of the whole virus. We concluded that genome size is an important factor in affecting the occurrence of SSRs; hosts are also responsible for the variances of SSRs content to a certain degree.


id: cord-001340-kqcx7lrq
title: Standards for Sequencing Viral Genomes in the Era of High-Throughput Sequencing
author: Ladner, Jason T.
date: 2014-06-17
txt: ./txt/cord-001340-kqcx7lrq.txt
cache: ./cache/cord-001340-kqcx7lrq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068259/
doi: 10.1128/mbio.01360-14
summary:
  Genome sequences play a critical role in our understanding of viral evolution, disease epidemiology, surveillance, diagnosis, and countermeasure development and thus represent valuable resources which must be properly documented and curated to ensure future utility. Here, we outline a set of viral genome quality standards, similar in concept to those proposed for large DNA genomes (4) but focused on the particular challenges of and needs for research on small RNA/ DNA viruses, including characterization of the genomic diversity inherent in all viral samples/populations. Therefore, we have used technology-agnostic criteria to define five standard categories designed to encompass the levels of completeness most often encountered in viral sequencing projects. There is a trend toward requiring a complete genome sequence when a description of a novel virus is being published, and we agree that this is a good goal; however, the amount of time and resources required to complete the last 1 to 2% of a viral genome is often cost and time prohibitive for projects sequencing a large number of samples, and in most cases the very ends of the segments are not essential for proper identification and characterization.

abstract:
  Thanks to high-throughput sequencing technologies, genome sequencing has become a common component in nearly all aspects of viral research; thus, we are experiencing an explosion in both the number of available genome sequences and the number of institutions producing such data. However, there are currently no common standards used to convey the quality, and therefore utility, of these various genome sequences. Here, we propose five “standard” categories that encompass all stages of viral genome finishing, and we define them using simple criteria that are agnostic to the technology used for sequencing. We also provide genome finishing recommendations for various downstream applications, keeping in mind the cost-benefit trade-offs associated with different levels of finishing. Our goal is to define a common vocabulary that will allow comparison of genome quality across different research groups, sequencing platforms, and assembly techniques.


id: cord-003316-r5te5xob
title: From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic
author: Balloux, Francois
date: 2018-12-17
txt: ./txt/cord-003316-r5te5xob.txt
cache: ./cache/cord-003316-r5te5xob.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249990/
doi: 10.1016/j.tim.2018.08.004
summary:
  WGS-based strain identification gives a far superior resolution In principle, WGS can provide highly relevant information for clinical microbiology in near-real-time, from phenotype testing to tracking outbreaks. As an example, genome assembly might appear to be a bottleneck for real-time WGS diagnostics, but is probably rarely required; sufficient characterization of an isolate can be made by analysis of the k-mers in the raw sequence data, which is orders of magnitude faster. These include, among others: the current costs of WGS, which remain far from negligible despite a common belief that sequencing costs have plummeted; a lack of training in, and possible cultural resistance to, bioinformatics among clinical microbiologists; a lack of the necessary computational infrastructure in most hospitals; the inadequacy of existing reference microbial genomics databases necessary for reliable AMR and virulence profiling; and the difficulty of setting up effective, standardized, and accredited bioinformatics protocols.

abstract:
  Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions.


id: cord-004123-1s8kuno2
author: Jaiswal, Arun Kumar
date: 2020-01-10
txt: ./txt/cord-004123-1s8kuno2.txt
cache: ./cache/cord-004123-1s8kuno2.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953169/
doi: 10.1186/s12864-019-6430-6
summary:
  title: The pan-genome of Treponema pallidum reveals differences in genome plasticity between subspecies related to venereal and non-venereal syphilis pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy. pertenue, we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study. In this work, we perform a pan-genome approach to better understand the differences of Treponema pallidum infections in the broad spectrum and how genome plasticity is related to the symptom patterns. Finally, we provide insights into the specific subsets (singletons and the panand core genomes) of 53 genomes of T pallidum strains and correlate these subsets with the plasticity of pathogenicity islands and virulence genes. The subspecies responsible for non-venereal syphilis is Treponema pallidum subsp. Genes which are present in pallidum subspecies pathogenicity islands (PAIs) or genomic islands (GIs) are absent in the subspecies endemicum and pertenue.

title:
  The pan-genome of Treponema pallidum reveals differences in genome plasticity between subspecies related to venereal and non-venereal syphilis

abstract:
  BACKGROUND: Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses. Pathogenic treponemes is a Gram-negative, motile, spirochete pathogen that causes syphilis in human. Treponema pallidum subsp. endemicum (TEN) causes endemic syphilis (bejel); T. pallidum subsp. pallidum (TPA) causes venereal syphilis; T. pallidum subsp. pertenue (TPE) causes yaws; and T. pallidum subsp. Ccarateum causes pinta. Out of these four high morbidity diseases, venereal syphilis is mediated by sexual contact; the other three diseases are transmitted by close personal contact. The global distribution of syphilis is alarming and there is an increasing need of proper treatment and preventive measures. Unfortunately, effective measures are limited. RESULTS: Here, the genome sequences of 53 T. pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy. Phylogenomic, pan-genomic, core genomic and singleton analysis disclosed the close connection among all strains of the pathogen T. pallidum, its clonal behaviour and showed increases in the sizes of the pan-genome. Based on the genome plasticity analysis of the subsets containing the subspecies T pallidum subsp. pallidum, T. pallidum subsp. endemicum and T. pallidum subsp. pertenue, we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study. CONCLUSIONS: In summary, we identified four pathogenicity islands (PAIs), eight genomic islands (GIs) in subsp. pallidum, whereas subsp. endemicum has three PAIs and seven GIs and subsp. pertenue harbours three PAIs and eight GIs. Concerning the presence of genes in PAIs and GIs, we found some genes related to lipid and amino acid biosynthesis that were only present in the subsp. of T. pallidum, compared to T. pallidum subsp. endemicum and T. pallidum subsp. pertenue.


id: cord-005281-wy0zk9p8
title: Viral component of the human genome
author: Blinov, V. M.
date: 2017-05-09
txt: ./txt/cord-005281-wy0zk9p8.txt
cache: ./cache/cord-005281-wy0zk9p8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089383/
doi: 10.1134/s0026893317020066
summary:
  In the human genome, this capacity is determined by the portion of chromosomal DNA, which does not contain species-specific protein-encoding sequences and, thus, can basically make a place for novel information that will be modified to reach a new balance. In fact, the scope of the described phenomena is not limited to retroviruses as such, since the ubiquity of retroviral elements in animal genomes, their activity in germline cells [31] , along with the fact that viral replication depends significantly on RNA expression, allow retroviruses to contribute in different ways to the insertion of nonretroviral genes into animal germline cells. Finally, the ability to incorporate parts of the viral genome into the chromosomal DNA of host germline cells can vary strongly among different taxonomic groups of viruses, i.e., orders, families, genera, and even species If insertions of viral sequences remain functionally active in the host cell genome, they can give rise to either proteins that function in a new environment or untranslated RNAs of different sizes.

abstract:
  Relationships between viruses and their human host are traditionally described from the point of view taking into consideration hosts as victims of viral aggression, which results in infectious diseases. However, these relations are in fact two-sided and involve modifications of both the virus and host genomes. Mutations that accumulate in the populations of viruses and hosts may provide them advantages such as the ability to overcome defense barriers of host cells or to create more efficient barriers to deal with the attack of the viral agent. One of the most common ways of reinforcing anti-viral barriers is the horizontal transfer of viral genes into the host genome. Within the host genome, these genes may be modified and extensively expressed to compete with viral copies and inhibit the synthesis of their products or modulate their functions in other ways. This review summarizes the available data on the horizontal gene transfer between viral and human genomes and discusses related problems.


id: cord-007923-j3jpqd7k
title: Cats
author: O''Brien, Stephen J.
date: 2004-12-14
txt: ./txt/cord-007923-j3jpqd7k.txt
cache: ./cache/cord-007923-j3jpqd7k.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7127084/
doi: 10.1016/j.cub.2004.11.017
abstract: nan
summary:
  Wild cats dominate their habitat but require vast expanses to survive, which explains the tragic depredation such that every species of Felidae, except the domestic cat, is considered either endangered or threatened in the wild today by CITES, IUCN Red Book and other monitors of the world''s most endangered species. Domestic cats and dogs enjoy more medical scrutiny than any species except humans. The cat offers the promise of a second carnivore species (in addition to the dog, which shares a common ancestor with cats dating back to approximately 60 million years ago) to improve human genome annotation, as well as to complement the biomedical and genomic discoveries that make the feline genome attractive. The conserved genome of the cat is retained in the other 36 Felidae species, as well as most of the 246 species of the Carnivora order, the only reshuffled exceptions occuring in the dog and bear families.


id: cord-012473-p66of6kq
title: Unlocking the secrets of the genome
author: Celniker, Susan E.
date: 2009-06-17
txt: ./txt/cord-012473-p66of6kq.txt
cache: ./cache/cord-012473-p66of6kq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843545/
doi: 10.1038/459927a
summary:
  T he primary objective of the Human Genome Project was to produce highquality sequences not just for the human genome but also for those of the chief model organisms: Escherichia coli, yeast (Saccharomyces cerevisiae), worm (Caenorhabditis elegans), fly (Drosophila melanogaster) and mouse (Mus musculus). Free access to the resultant data has prompted much biological research, including development of a map of common human genetic variants (the International HapMap Project) 1 , expression profiling of healthy and diseased cells 2 and in-depth studies of many individual genes. On the basis of this experience, the NHGRI launched two complementary programmes in 2007: an expansion of the human ENCODE project to the whole genome (www.genome.gov/ENCODE) and the model organism ENCODE (modENCODE) project to generate a comprehensive annotation of the functional elements in the C. The research communities that study these two organisms will rapidly make use of the modENCODE results, deploying powerful experimental approaches that are often not possible or practical in mammals, including genetic, genomic, transgenic, biochemical and RNAi assays.

abstract:
  Despite the successes of genomics, little is known about how genetic information produces complex organisms. A look at the crucial functional elements of fly and worm genomes could change that. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/459927a) contains supplementary material, which is available to authorized users.


id: cord-014461-2ubh9u8r
title: Genome sequences published outside of Standards in Genomic Sciences, July - October 2012
author: Nelson, Oranmiyan W.
date: 2012-10-10
txt: ./txt/cord-014461-2ubh9u8r.txt
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3570808/
doi: 10.4056/sigs.3416907
summary:
  Complete Genome Sequence of Brucella abortus A13334, a New Strain Isolated from the Fetal Gastric Fluid of Dairy Cattle Complete Genome Sequence of Brucella canis Strain HSK A52141, Isolated from the Blood of an Infected Dog Complete Genome Sequence of Streptococcus salivarius PS4, a Strain Isolated from Human Milk Complete Genome Sequences of Probiotic Strains Bifidobacterium animalis subsp. Complete Genome Sequence of Corynebacterium pseudotuberculosis Strain 1/06-A, Isolated from a Horse in North America Complete Genome Sequence of Bacteriophage BC-611 Specifically Infecting Enterococcus faecalis Strain NP-10011 Complete Genome Sequence of Bacteriophage BC-611 Specifically Infecting Enterococcus faecalis Strain NP-10011 Characterization and Complete Genome Sequence of Human Coronavirus NL63 Isolated in China Complete Genome Sequence of a Novel Pararetrovirus Isolated from Soybean Complete Genome Sequence of a Polyomavirus Isolated from Horses Complete Genome Sequence of a Novel Porcine Sapelovirus Strain YC2011 Isolated from Piglets with Diarrhea Draft Genome Sequence of Aspergillus oryzae Strain 3.042

abstract:
  The purpose of this table is to provide the community with a citable record of publications of ongoing genome sequencing projects that have led to a publication in the scientific literature. While our goal is to make the list complete, there is no guarantee that we may have omitted one or more publications appearing in this time frame. Readers and authors who wish to have publications added to subsequent versions of this list are invited to provide the bibliographic data for such references to the SIGS editorial office.


id: cord-015850-ef6svn8f
title: Eukaryote Genomes
author: Saitou, Naruya
date: 2013-08-22
txt: ./txt/cord-015850-ef6svn8f.txt
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119937/
doi: 10.1007/978-1-4471-5304-7_8
summary:
  General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Most of the protein coding genes of melon mitochondrial DNAs are highly similar to those of its congeneric species, which are watermelon and squash whose mitochondrial genome sizes are 119 kb and 125 kb, respectively. There are various genomic features that are specifi c to eukaryotes other than existence of introns and junk DNAs, such as genome duplication, RNA editing, C-value paradox, and the relationship between genome size and mutation rates. The Perigord black truffl e ( Tuber melanosporum ), shown as A i n Fig. 8.9 , has the largest genome size (~125 Mb) among the 88 fungi species whose genome sequences were so far determined, yet the number of genes is only ~7,500 [ 81 ] .

abstract:
  General overviews of eukaryote genomes are first discussed, including organelle genomes, introns, and junk DNAs. We then discuss the evolutionary features of eukaryote genomes, such as genome duplication, C-value paradox, and the relationship between genome size and mutation rates. Genomes of multicellular organisms, plants, fungi, and animals are then briefly discussed.


id: cord-016588-f8uvhstb
title: Informatics for Infectious Disease Research and Control
author: Sintchenko, Vitali
date: 2009-10-03
txt: ./txt/cord-016588-f8uvhstb.txt
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7120928/
doi: 10.1007/978-1-4419-1327-2_1
summary:
  The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. "New Age" infectious disease informatics rests on advances in microbial genomics, the sequencing and comparative study of the genomes of pathogens, and proteomics or the identification and characterization of their protein related properties and reconstruction of metabolic and regulatory pathways (Bansal 2005) . The figure was produced using Artemis software (The Wellcome Trust Sanger Institute, UK) 1 Informatics for Infectious Disease Research and Control evidence-based gene calling or translating alignments of the DNA sequence to known proteins; and (3) aligning cDNAs from the same or related species.

abstract:
  The goal of infectious disease informatics is to optimize the clinical and public health management of infectious diseases through improvements in the development and use of antimicrobials, the design of more effective vaccines, the identification of biomarkers for life-threatening infections, a better understanding of host-pathogen interactions, and biosurveillance and clinical decision support. Infectious disease informatics can lead to more targeted and effective approaches for the prevention, diagnosis and treatment of infections through a comprehensive review of the genetic repertoire and metabolic profiles of a pathogen. The developments in informatics have been critical in boosting the translational science and in supporting both reductionist and integrative research paradigms.


id: cord-016798-tv2ntug6
title: Bioinformatics Applications in Advancing Animal Virus Research
author: Gautam, Ablesh
date: 2019-06-06
txt: ./txt/cord-016798-tv2ntug6.txt
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121192/
doi: 10.1007/978-981-13-9073-9_23
summary:
  The chapter further provides information on the tools that can be used to study viral epidemiology, phylogenetic analysis, structural modelling of proteins, epitope recognition and open reading frame (ORF) recognition and tools that enable to analyse host-viral interactions, gene prediction in the viral genome, etc. This chapter will introduce virologists to some of the common as well virus-specific bioinformatics tools that the researches can use to analyse viral sequence data to elucidate the viral dynamics, evolution and preventive therapeutics. Novel virus types comprise of new CDSs that are different than previously known CDSs. There are multiple databases and tools available for analysis of human viruses; however, there are still only a limited number of resources designed specifically for veterinary viruses. VIRsiRNAdb is an online curated repository that stores experimentally validated research data of siRNA and short hairpin RNA (shRNA) targeting diverse genes of 42 important human viruses, including influenza virus (Tyagi et al.

abstract:
  Viruses serve as infectious agents for all living entities. There have been various research groups that focus on understanding the viruses in terms of their host-viral relationships, pathogenesis and immune evasion. However, with the current advances in the field of science, now the research field has widened up at the ‘omics’ level. Apparently, generation of viral sequence data has been increasing. There are numerous bioinformatics tools available that not only aid in analysing such sequence data but also aid in deducing useful information that can be exploited in developing preventive and therapeutic measures. This chapter elaborates on bioinformatics tools that are specifically designed for animal viruses as well as other generic tools that can be exploited to study animal viruses. The chapter further provides information on the tools that can be used to study viral epidemiology, phylogenetic analysis, structural modelling of proteins, epitope recognition and open reading frame (ORF) recognition and tools that enable to analyse host-viral interactions, gene prediction in the viral genome, etc. Various databases that organize information on animal and human viruses have also been described. The chapter will converse on overview of the current advances, online and downloadable tools and databases in the field of bioinformatics that will enable the researchers to study animal viruses at gene level.


id: cord-017932-vmtjc8ct
title: Genomic and Postgenomic Research
author: Georgiev, Vassil St.
date: 2009
txt: ./txt/cord-017932-vmtjc8ct.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122628/
doi: 10.1007/978-1-60327-297-1_25
summary:
  The family Enterobacteriaceae encompasses a diverse group of bacteria including many of the most important human pathogens (Salmonella, Yersinia, Klebsiella, Shigella), as well as one of the most enduring laboratory research organisms, the nonpathogenic Escherichia coli K12. To this end, NIAID has made significant investments in large-scale sequencing projects, including projects to sequence the complete genomes of many pathogens, such as the bacteria that cause tuberculosis, gonorrhea, chlamydia, and cholera, as well as organisms that are considered agents of bioterrorism. The availability of microbial and human DNA sequences opens up new opportunities and allows scientists to perform functional analyses of genes and proteins in whole genomes and cells, as well as the host''s immune response and an individual''s genetic susceptibility to pathogens. The PFGRC was established in 2001 to provide and distribute to the broader research community a wide range of genomic resources, reagents, data, and technologies for the functional analysis of microbial pathogens and invertebrate vectors of infectious diseases.

abstract:
  The word genomics was first coined by T. Roderick from the Jackson Laboratories in 1986 as the name for the new field of science focused on the analysis and comparison of complete genome sequences of organisms and related high-throughput technologies.


id: cord-018437-yjvwa1ot
title: Taxonomy
author: Mitchell, Michael
date: 2013-08-26
txt: ./txt/cord-018437-yjvwa1ot.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123310/
doi: 10.1007/978-3-642-40605-8_3
summary:
  Classifi cation is based on the genomic nucleic acid used by the virus (DNA or RNA), strandedness (single or double stranded), and method of replication. The nucleocapsids of some viruses are surrounded by envelopes composed of lipid bilayers and host-or viral-encoded proteins. The sequence of negative-sense ssRNA is complementary to the coding sequence for translation, so mRNA must be synthesized by RNA polymerase, typically carried within the virion, before translation into viral proteins. Among the families of viruses able to infect humans and other vertebrate hosts, there are many species that target and cause disease in the lung. The nucleocapsid is surrounded by an envelope derived from host-cell membrane and viral envelope proteins, including hepatitis B surface antigen. The genome of human parainfl uenza viruses is ~15 kb in length with an organization and six reading frames (N, P, M, F, HN, L) typical of the Paramyxoviridae (Karron and Collins 2007 ) .

abstract:
  This chapter addresses the classification and taxonomy of viruses with special attention to viruses that show pneumotropic properties. Information provided in this chapter supplements that provided in other chapters in Parts II–V of this volume that discuss individual viral pathogens.


id: cord-018804-wj35q88f
author: Lázaro, Ester
date: 2007
txt: ./txt/cord-018804-wj35q88f.txt
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url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123777/
doi: 10.1007/978-3-540-35306-5_15
abstract: nan
summary:
  High error prone replication, together with the short replication times and large population sizes typical of RNA viruses, instead of being a handicap for survival provides an extraordinary evolutionary advantage by permitting the generation of a wide reservoir of mutants with different phenotypic properties [7] . However, the fact that DNA organisms, which usually live in constant environments, have evolved corrector activities, whereas RNA viruses have not, suggests that replication with high error rates is a selected character that strongly favours viral adaptation to fast changing conditions. Quasi-species replicating during a long time in a near-constant environment in the absence of large population size fluctuations can present a low rate of fixation of mutations in the consensus sequence, despite the continuous occurrence of mutants that is characteristic of the underlying dynamics of the population. The infection of a new host constitutes a sudden change in the environment in which viral replication takes place, usually with the consequence of a drastic decrease in the average fitness of the virus population, which prevents further transmission.

title:
  Genetic Variability in RNA Viruses: Consequences in Epidemiology and in the Development of New Stratgies for the Extinction of Infectivity


id: cord-022128-r8el8nqm
title: Molecular basis of genetic variation of viruses: error-prone replication
author: Domingo, Esteban
date: 2019-11-08
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153327/
doi: 10.1016/b978-0-12-816331-3.00002-7
abstract:
  Genetic variation is a necessity of all biological systems. Viruses use all known mechanisms of variation; mutation, several forms of recombination, and segment reassortment in the case of viruses with a segmented genome. These processes are intimately connected with the replicative machineries of viruses, as well as with fundamental physical-chemical properties of nucleotides when acting as template or substrate residues. Recombination has been viewed as a means to rescue viable genomes from unfit parents or to produce large modifications for the exploration of phenotypic novelty. All types of genetic variation can act conjointly as blind processes to provide the raw materials for adaptation to the changing environments in which viruses must replicate. A distinction is made between mechanistically unavoidable and evolutionarily relevant mutation and recombination.


id: cord-022262-ck2lhojz
title: Genetics, Pathogenesis and Evolution of Picornaviruses
author: Gromeier, Matthias
date: 2007-09-02
txt: ./txt/cord-022262-ck2lhojz.txt
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mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155501/
doi: 10.1016/b978-012220360-2/50013-1
summary:
  The following viruses have been recognized as picornaviruses on the basis of their genome sequences and physico-chemical properties as well as the result of comparative sequence analyses (see the section on Evolution): equine rhinovirus types I and 2, Aichi virus, porcine enterovirus, avian encephalomyelitis virus, infectious flacherie virus of silkworm Clusters of enteroviruses refer to groups of enteroviruses arranged predominantly according to genotypic kinship (Hyypia et al., 1997) . Briefly, when expression vectors ( Figure 12 .6E) consisting of a gag gene (encoding p17-p24; 1161 nt) of human immunodeficiency virus that was fused to the N-terminus of the poliovirus polyprotein (Andino et al., 1994; Mueller and Wimmer, 1998) were analysed after transfection into HeLa cells, the genomes were not only found to be severely impaired in viral replication but they were also genetically unstable (Mueller and Wimmer, 1997) .

abstract:
  The discovery of viruses heralded an exciting new era for research in the medical and biological sciences. It has been realized that the cellular receptor guiding a virus to a target cell cannot be the sole determinant of a virus's pathogenic potential. Comparative analyses of the structures of genomes and their products have placed the picornaviruses into a large “picorna-like” virus family, in which they occupy a prominent place. Most human picornavirus infections are self-limiting, yet the enormously high rate of picornavirus infections in the human population can lead to a significant incidence of disease complications that may be permanently debilitating or even fatal. Picornaviruses employ one of the simplest imaginable genetic systems: they consist of single-stranded RNA that encodes only a single multidomain polypeptide, the polyprotein. The RNA is packaged into a small, rigid, naked, and icosahedral virion whose proteins are unmodified except for a myristate at the N-termini of VP4. The RNA itself does not contain modified bases. The key to ultimately understanding picornaviruses may be to rationalize the huge amount of information about these viruses from the perspective of evolution. It is possible that the replicative apparatus of picornaviruses originated in the precellular world and was subsequently refined in the course of thousands of generations in a slowly evolving environment. Picornaviruses cultivated the art of adaptation, which has allowed them to “jump” into new niches offered in the biological world.


id: cord-264746-gfn312aa
title: GENOMICS AND BIOINFORMATICS
author: Muse, Spencer
date: 2012-03-29
txt: ./txt/cord-264746-gfn312aa.txt
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mime: text/plain
url: https://api.elsevier.com/content/article/pii/B978012238662650015X
doi: 10.1016/b978-0-12-238662-6.50015-x
summary:
  The success of this project (it came in almost 3 years ahead of time and 10% under budget, while at the same time providing more data than originally planned) depended on innovations in a variety of areas: breakthroughs in basic molecular biology to allow manipulation of DNA and other compounds; improved engineering and manufacturing technology to produce equipment for reading the sequences of DNA; advances in robotics and laboratory automation; development of statistical methods to interpret data from sequencing projects; and the creation of specialized computing hardware and software systems to circumvent massive computational barriers that faced genome scientists. Although the list of important biotechnologies changes on an almost daily basis, there are three prominent data types in today''s environment: (1) genome sequences provide the starting point that allows scientists to begin understanding the genetic underpinnings of an organism; (2) measurements of gene expression levels facilitate studies of gene regulation, which, among other things, help us to understand how an organism''s genome interacts with its environment; and (3) genetic polymorphisms are variations from individual to individual within species, and understanding how these variations correlate with phenotypes such as disease susceptibility is a crucial element of modern biomedical research.

abstract:
  This chapter discusses the basic principles of molecular biology regarding genome science and describes the major types of data involved in genome projects, including technologies for collecting them. Genome science is heavily driven by new technological advances that allow for rapid and inexpensive collection of various types of data. The emergence of genomic science has not simply provided a rich set of tools and data for studying molecular biology. It has been the catalyst for an astounding burst of interdisciplinary research, and it has challenged long-established hierarchies found in most institutions of higher learning. The next generation of biologists needs to be as comfortable at a computer workstation as they are at the lab bench. Recognizing this fact, many universities have already reorganized their departments and their curricula to accommodate the demands of genomic science.The chapter discusses practical applications and uses of genomic data. For example, in the foreseeable future, are gene therapies that can repair genetic defects.


id: cord-265329-bsypo08l
title: Emergence of genomic diversity and recurrent mutations in SARS-CoV-2
author: van Dorp, Lucy
date: 2020-05-05
txt: ./txt/cord-265329-bsypo08l.txt
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extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/S1567134820301829
doi: 10.1016/j.meegid.2020.104351
summary:
  Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. The extraordinary availability of genomic data during the COVID-19 pandemic has been made possible thanks to a tremendous effort by hundreds of researchers globally depositing SARS-CoV-2 assemblies (Table S1 ) and the proliferation of close to real time data visualisation and analysis tools including NextStrain (https://nextstrain.org) and CoV-GLUE (http://cov-glue.cvr.gla.ac.uk). In this work we use this data to analyse the genomic diversity that has emerged in the global population of SARS-CoV-2 since the beginning of the COVID-19 pandemic, based on a download of 7710 assemblies. The genomic diversity of the global SARS-CoV-2 population being recapitulated in multiple countries points to extensive worldwide transmission of COVID-19, likely from extremely early on in the pandemic.

abstract:
  SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.


id: cord-265581-pbv8mjfc
title: An aurora of natural products-based drug discovery is coming
author: Tong, Yaojun
date: 2020-06-06
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url: https://www.ncbi.nlm.nih.gov/pubmed/32537523/
doi: 10.1016/j.synbio.2020.05.003
summary:
  With recent scientific advances combining metabolic sciences and technology, multi-omics, big data, combinatorial biosynthesis, synthetic biology, genome editing technology (such as CRISPR), artificial intelligence (AI), and 3D printing, the "high-hanging fruit" is becoming more and more accessible with reduced costs. The incredible rate of development in genome sequencing, modern metabolic engineering, synthetic biology, advanced genome editing, big data, artificial intelligence (AI), and 3D printing together with the growing microbial strain collections enable us to access the previously inaccessible natural products. It starts with genome mining (the analysis of high quality whole genome information), which requires bioinformatics, big data, and even AI; to pathway cloning (refactoring), expression and fermentation, which needs design-buildtest-learn (DBTL) cycle-based metabolic engineering; to the target natural product identification, which requires modern chemical analysis; and to later compound modification and clinical studies, which needs biochemistry and cell biology.

abstract:
  Natural products (NPs), a nature's reservoir possessing enormous structural and functional diversity far beyond the current ability of chemical synthesis, are now proving themselves as most wonderful gifts from mother nature for human beings. Many of them have been used successfully as medicines, as well as the most important sources of drug leads, food additives, and many industry relevant products for millennia. Most notably, more than half of the antibiotics and anti-cancer drugs currently in use are, or derived from, natural products. However, the speed and outputs of NP-based drug discovery has been slowing down dramatically after the fruitful harvest of the “low-hanging fruit” during the golden age of 1950s-1960s. With recent scientific advances combining metabolic sciences and technology, multi-omics, big data, combinatorial biosynthesis, synthetic biology, genome editing technology (such as CRISPR), artificial intelligence (AI), and 3D printing, the “high-hanging fruit” is becoming more and more accessible with reduced costs. We are now more and more confident that a new age of natural products discovery is dawning.


id: cord-265857-fs6dj3dp
title: Infectious Disease Genomics
author: Liu, Yu-Tsueng
date: 2010-12-24
txt: ./txt/cord-265857-fs6dj3dp.txt
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mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780123848901000108
doi: 10.1016/b978-0-12-384890-1.00010-8
summary:
  The completed or ongoing genome projects will provide enormous opportunities for the discovery of novel vaccines and drug targets against human pathogens as well as the improvement of diagnosis and discovery of infectious agents and the development of new strategies for invertebrate vector control. The genomes of human malaria parasite Plasmodium falciparum and its major mosquito vector Anopheles gambiae were published in 2002 (Gardner et al., 2002; Holt et al., 2002) . Genome sequencing projects for other important human disease vectors are in progress Megy et al., 2009 ). One of the similar efforts for human pathogens is the NIH Influenza Genome Sequencing Project. The completed or ongoing genome projects (Table 10 .1) will provide enormous opportunities for the discovery of novel vaccines and drug targets against human pathogens as well as the improvement of diagnosis and discovery of infectious agents and the development of new strategies for invertebrate vector control.

abstract:
  The history and development of infectious disease genomics are discussed in this chapter. HGP must not be restricted to the human genome and should include model organisms including mouse, bacteria, yeast, fruit fly, and worm. The completed or ongoing genome projects will provide enormous opportunities for the discovery of novel vaccines and drug targets against human pathogens as well as the improvement of diagnosis and discovery of infectious agents and the development of new strategies for invertebrate vector control. The polysaccharide capsule is important for meningococci to escape from complement-mediated killing. With the completion of the genome sequence of a virulent MenB strain, a “reverse vaccinology” approach was applied for the development of a universal MenB vaccine by Novartis. The indispensable fatty acid synthase (FAS) pathway in bacteria has been regarded as a promising target for the development of antimicrobial agents. Through a systematic screening of 250,000 natural product extracts, a Merck team identified a potent and broad-spectrum antibiotic, platensimycin, which is derived from Streptomyces platensis. Vector Biology Network was formed to achieve three goals (1) to develop basic tools for the stable transformation of anopheline mosquitoes by the year 2000; (2) to engineer a mosquito incapable of carrying the malaria parasite by 2005; and (3) to run controlled experiments to test how to drive the engineered genotype into wild mosquito populations by 2010. The most immediate impact of a completely sequenced pathogen genome is for infectious disease diagnosis.


id: cord-267714-ji88tvsl
title: Biological agent detection technologies
author: JAKUPCIAK, JOHN P.
date: 2009-04-21
txt: ./txt/cord-267714-ji88tvsl.txt
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mime: text/plain
url: https://doi.org/10.1111/j.1755-0998.2009.02632.x
doi: 10.1111/j.1755-0998.2009.02632.x
summary:
  PCR-based methods have critical limitations, since they depend on a priori knowledge of what sequence to detect in a sample further complicated by recent demonstrations of greater variability in genomic sequence than expected. A platform for genome identification of a specimen from any source must not only be sensitive and specific, but must also detect a variety of pathogens with high accuracy, including modified or previously uncharacterized agents, and this challenge is daunting when identification must be achieved using nucleic acids in a complex sample matrix. The build-out of genome identification DNA sequencing technology in the form of practical instrumentation will be achieved by incorporating the critical requirements for accurate long reads, without dependency for template amplification, capable of manipulating terabytes of data to provide reliable and useful identification of genetic sequences within any unknown sample, whether clinical, environmental, or other type of specimen.

abstract:
  The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today. There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro‐organisms, forensics, environmental sampling for detect‐to‐treat applications, biological sensors for ‘detect to warn’ in infrastructure protection, responses to reports of ‘suspicious powders’, and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures.


id: cord-268795-tjmx6msm
author: Sardar, Rahila
date: 2020-03-21
txt: ./txt/cord-268795-tjmx6msm.txt
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mime: text/plain
url: https://doi.org/10.1101/2020.03.21.001586
doi: 10.1101/2020.03.21.001586
summary:
  title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Our analysis shows unique host-miRNAs targeting SARS-CoV2 virus genes. CELLO2GO (7)server was used to infer biological function for each protein of SARS-CoV2 genome with their localization prediction. Assembled SARS-CoV2 genomes sequences in FASTA format from India, USA, China, Italy and Nepal used for coronavirus typing tool analysis. For the phylogenetic analysis, we compared the sequences of 6 SARS-CoV2 isolates from different countries namely, Wuhan, India, Italy, USA and Nepal along with other corona virus species ( Figure 1 ).

title:
  Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis

abstract:
  The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. The phylogeny of the genomes yields some interesting results. Systematic gene level mutational analysis of the genomes has enabled us to identify several unique features of the SARS-CoV2 genome, which includes a unique mutation in the spike surface glycoprotein (A930V (24351C>T)) in the Indian SARS-CoV2, absent in other strains studied here. We have also predicted the impact of the mutations in the spike glycoprotein function and stability, using computational approach. To gain further insights into host responses to viral infection, we predict that antiviral host-miRNAs may be controlling the viral pathogenesis. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Interestingly, the nine miRNAs do not have targets in SARS and MERS genomes. Also, hsa-miR-27b is the only unique miRNA which has a target gene in the Indian SARS-CoV2 genome. We also predicted immune epitopes in the genomes


id: cord-269124-oreg7rnj
title: Ancient pathogen genomics as an emerging tool for infectious disease research
author: Spyrou, Maria A.
date: 2019-04-05
txt: ./txt/cord-269124-oreg7rnj.txt
cache: ./cache/cord-269124-oreg7rnj.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1038/s41576-019-0119-1
doi: 10.1038/s41576-019-0119-1
summary:
  Examples of tools that have shown their effectiveness with ancient metagenomic DNA include the widely used Basic Local Alignment Search Tool (BLAST) 68 ; the MEGAN Alignment Tool (MALT) 41 , which involves a taxonomic binning algorithm that can use whole genome databases (such as the National Center for Biotechnical Information (NCBI) Reference Sequence (RefSeq) database 69 ); Metagenomic Phylogenetic Analysis (MetaPhlAn) 70 , which is also integrated into the metagenomic pipeline MetaBIT 71 and uses thousands (or millions) of marker genes for the distinction of specific microbial clades; or Kraken 72 , an alignment free sequence classifier that is based on k-mer matching of a query to a constructed database. Similar limitations can arise when the evolutionary history of a microorganism is vastly affected by recombination, as observed for HBV 44, 53 , although HBV molecular dating was recently attempted using a different genomic data set and suggested that the currently explored diversity of Old and New World pri mate lineages (including all human genotypes) may have emerged within the last 20,000 years 43 .

abstract:
  Over the past decade, a genomics revolution, made possible through the development of high-throughput sequencing, has triggered considerable progress in the study of ancient DNA, enabling complete genomes of past organisms to be reconstructed. A newly established branch of this field, ancient pathogen genomics, affords an in-depth view of microbial evolution by providing a molecular fossil record for a number of human-associated pathogens. Recent accomplishments include the confident identification of causative agents from past pandemics, the discovery of microbial lineages that are now extinct, the extrapolation of past emergence events on a chronological scale and the characterization of long-term evolutionary history of microorganisms that remain relevant to public health today. In this Review, we discuss methodological advancements, persistent challenges and novel revelations gained through the study of ancient pathogen genomes.


id: cord-275683-1qj9ri18
title: Metagenomics in Virology
author: Roux, Simon
date: 2019-06-12
txt: ./txt/cord-275683-1qj9ri18.txt
cache: ./cache/cord-275683-1qj9ri18.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780128096338209576
doi: 10.1016/b978-0-12-809633-8.20957-6
summary:
  Against the background of an extensive viral diversity revealed by metagenomics across many environments, new sequence assembly approaches that reconstruct complete genome sequences from metagenomes have recently revealed surprisingly cosmopolitan viruses in specific ecological niches. However, these techniques can only detect previously known viruses, and often require Box 1 Use of complementary methods to target different types of viruses A number of approaches have been developed to specifically select and survey the genetic material contained by virus particles in a given sample. Virus sequences obtained from "bulk" metagenomes will typically reflect viruses infecting their host cell at the time of sampling, either actively replicating or not, while viromes enables a deeper and more focused exploration of the virus diversity in a specific site or sample. With viral metagenomics being applied to a larger set of samples and environments, and with bioinformatic analyses including genome assembly and interpretation constantly improving, novel groups of dominant and widespread viruses may thus be progressively revealed across many environments.

abstract:
  Metagenomics, i.e., the sequencing and analysis of genomic information extracted directly from clinical or environmental samples, has become a fundamental tool to explore the viral world. Against the background of an extensive viral diversity revealed by metagenomics across many environments, new sequence assembly approaches that reconstruct complete genome sequences from metagenomes have recently revealed surprisingly cosmopolitan viruses in specific ecological niches. Metagenomics is also applied to clinical samples as a non-targeted diagnostic and surveillance tool. By enabling the study of these uncultivated viruses, metagenomics provides invaluable insights into the virus-host interactions, epidemiology, ecology, and evolution of viruses across all ecosystems.


id: cord-277687-u3q36o3e
author: Shean, Ryan C.
date: 2019-01-23
txt: ./txt/cord-277687-u3q36o3e.txt
cache: ./cache/cord-277687-u3q36o3e.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/30674273/
doi: 10.1186/s12859-019-2606-y
summary:
  title: VAPiD: a lightweight cross-platform viral annotation pipeline and identification tool to facilitate virus genome submissions to NCBI GenBank In order to accept submitted viral genomic data, NCBI GenBank requires 1) viral sequence complete with at least one protein annotation, 2) author/depositor metadata, and 3) viral sequence metadata, such as strain, collection date, collection location, and coverage. VAPiD handles batch submissions of multiple viruses of different types without prior knowledge of the viral species, correctly annotates RNA editing and ribosomal slippage, performs spellchecking on annotations, handles batch or individual submission of metadata, runs with a simple one-line command, and creates annotated viral sequence files for GenBank submission. This first example is the task that the authors originally wrote VAPiD for -annotating large numbers of genomes from different viral species, which mirrors the type of data that many clinical and public health laboratories may encounter.

title:
  VAPiD: a lightweight cross-platform viral annotation pipeline and identification tool to facilitate virus genome submissions to NCBI GenBank

abstract:
  BACKGROUND: With sequencing technologies becoming cheaper and easier to use, more groups are able to obtain whole genome sequences of viruses of public health and scientific importance. Submission of genomic data to NCBI GenBank is a requirement prior to publication and plays a critical role in making scientific data publicly available. GenBank currently has automatic prokaryotic and eukaryotic genome annotation pipelines but has no viral annotation pipeline beyond influenza virus. Annotation and submission of viral genome sequence is a non-trivial task, especially for groups that do not routinely interact with GenBank for data submissions. RESULTS: We present Viral Annotation Pipeline and iDentification (VAPiD), a portable and lightweight command-line tool for annotation and GenBank deposition of viral genomes. VAPiD supports annotation of nearly all unsegmented viral genomes. The pipeline has been validated on human immunodeficiency virus, human parainfluenza virus 1–4, human metapneumovirus, human coronaviruses (229E/OC43/NL63/HKU1/SARS/MERS), human enteroviruses/rhinoviruses, measles virus, mumps virus, Hepatitis A-E Virus, Chikungunya virus, dengue virus, and West Nile virus, as well the human polyomaviruses BK/JC/MCV, human adenoviruses, and human papillomaviruses. The program can handle individual or batch submissions of different viruses to GenBank and correctly annotates multiple viruses, including those that contain ribosomal slippage or RNA editing without prior knowledge of the virus to be annotated. VAPiD is programmed in Python and is compatible with Windows, Linux, and Mac OS systems. CONCLUSIONS: We have created a portable, lightweight, user-friendly, internet-enabled, open-source, command-line genome annotation and submission package to facilitate virus genome submissions to NCBI GenBank. Instructions for downloading and installing VAPiD can be found at https://github.com/rcs333/VAPiD.


id: cord-281959-g4sjyytr
title: Efficient oligonucleotide probe selection for pan-genomic tiling arrays
author: Phillippy, Adam M
date: 2009-09-16
txt: ./txt/cord-281959-g4sjyytr.txt
cache: ./cache/cord-281959-g4sjyytr.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1186/1471-2105-10-293
doi: 10.1186/1471-2105-10-293
summary:
  The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. In order to both characterize new strains based on genetic content, and detect polymorphism at a higher resolution in small RNAs (sRNAs) and intergenic sequences, the array was required to cover all pan-genomic sequences with a high density of probes. To see the similarities between the Pan-Tiling and Minimum Hitting Set problems, let the sequence G be a concatenation of all the genomes from a species, and let W = {w 1 , w 2 ,..., w m } be the set of m intervals that results from segmenting G into non-overlapping, end-to-end, length l windows.

abstract:
  BACKGROUND: Array comparative genomic hybridization is a fast and cost-effective method for detecting, genotyping, and comparing the genomic sequence of unknown bacterial isolates. This method, as with all microarray applications, requires adequate coverage of probes targeting the regions of interest. An unbiased tiling of probes across the entire length of the genome is the most flexible design approach. However, such a whole-genome tiling requires that the genome sequence is known in advance. For the accurate analysis of uncharacterized bacteria, an array must query a fully representative set of sequences from the species' pan-genome. Prior microarrays have included only a single strain per array or the conserved sequences of gene families. These arrays omit potentially important genes and sequence variants from the pan-genome. RESULTS: This paper presents a new probe selection algorithm (PanArray) that can tile multiple whole genomes using a minimal number of probes. Unlike arrays built on clustered gene families, PanArray uses an unbiased, probe-centric approach that does not rely on annotations, gene clustering, or multi-alignments. Instead, probes are evenly tiled across all sequences of the pan-genome at a consistent level of coverage. To minimize the required number of probes, probes conserved across multiple strains in the pan-genome are selected first, and additional probes are used only where necessary to span polymorphic regions of the genome. The viability of the algorithm is demonstrated by array designs for seven different bacterial pan-genomes and, in particular, the design of a 385,000 probe array that fully tiles the genomes of 20 different Listeria monocytogenes strains with overlapping probes at greater than twofold coverage. CONCLUSION: PanArray is an oligonucleotide probe selection algorithm for tiling multiple genome sequences using a minimal number of probes. It is capable of fully tiling all genomes of a species on a single microarray chip. These unique pan-genome tiling arrays provide maximum flexibility for the analysis of both known and uncharacterized strains.


id: cord-297669-22fctxk4
title: Genome editing for disease resistance in pigs and chickens
author: Proudfoot, Chris
date: 2019-06-25
txt: ./txt/cord-297669-22fctxk4.txt
cache: ./cache/cord-297669-22fctxk4.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1093/af/vfz013
doi: 10.1093/af/vfz013
abstract: nan
summary:
  The virus was thought to attach to CD169 to be taken up into the cells; however, genome-edited pigs lacking CD169 were not resistant to PRRSV infection (Prather et al., 2013) . Chicken somatic cell lines have been edited to introduce changes to this gene-conferring resistance to avian leucosis virus in vitro (Lee et al., 2017) . However, as the example for avian influenza shows, host genes play an important role in other steps of the pathogen replication cycle and also provide editing targets for disease resilience or resistance. Genome editing allows integration of the disease-resistance trait into a wider selection of pigs, ensuring genetic variability and maintenance of desirable traits. (D) Resistance genes may be identified in laboratory research but not in highly bred lines, making integration into those productive animals only possible using genome editing. She employs genome editing and genetic selection to generate animals genetically resistant to viral disease.


id: cord-298136-mel9fxw8
title: Whole-genome patenting
author: O''Malley, Maureen A.
date: 2005-05-10
txt: ./txt/cord-298136-mel9fxw8.txt
cache: ./cache/cord-298136-mel9fxw8.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15883589/
doi: 10.1038/nrg1613
summary:
  Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. However, further analysis reveals that patent specifications describing whole-genome inventions use arguments that imply that genomes are qualitatively different from individual genes. This standard allows several sub-inventions to be linked together by a common "general inventive concept", but prevents unrelated inventions from succeeding as a single Abstract | Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. If there are any qualitative differences between patents for whole genomes and those for DNA fragments, it seems likely that they will be found in the utility arguments -the most contested feature of recent gene patenting.

abstract:
  Gene patenting is now a familiar commercial practice, but there is little awareness that several patents claim ownership of the complete genome sequence of a prokaryote or virus. When these patents are analysed and compared to those for other biological entities, it becomes clear that genome patents seek to exploit the genome as an information base and are part of a broader shift towards intangible intellectual property in genomics.


id: cord-301709-kvyes2lz
title: Developing Bioinformatic Resources for Coronaviruses
author: Baker, Susan C.
date: 2006
txt: ./txt/cord-301709-kvyes2lz.txt
cache: ./cache/cord-301709-kvyes2lz.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/17037566/
doi: 10.1007/978-0-387-33012-9_70
abstract: nan
summary:
  The database will contain high-quality curated data: sequence annotations from published whole and partial genomes; relevant experimental data; metabolic pathway data; taxonomic data; literature citations; and a suite of visualization and analysis tools. The results of these programs and searches assembled by the annotation pipeline are used to propose biological features that are also stored in the curation database that uses the Genomics Unified Schema (GUS). For the purposes of defining minimal, non-redundant set of genes characteristic of the category, one genome (usually the best-known or best-characterized) is identified as the "reference genome"; the remaining members of the class are called "associated genomes." For example, the Tor2 and Urbani isolates were the first two SARS coronavirus genomes to be sequenced and therefore were named as reference genomes. This allows high-value, manually curated information from the corresponding reference genes to be automatically linked to the associated genes, provided minimal similarity criteria based on automated sequence analysis are satisfied.


id: cord-302047-vv5gpldi
title: On the stability of sequences inserted into viral genomes
author: Willemsen, Anouk
date: 2019-11-14
txt: ./txt/cord-302047-vv5gpldi.txt
cache: ./cache/cord-302047-vv5gpldi.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/31741748/
doi: 10.1093/ve/vez045
summary:
  Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Viruses genera covered in relevant studies Conclusions of this review All viruses • Inserted sequences are often unstable and rapidly lost upon passaging of an engineered virus • The position at which a sequence is integrated in the genome can be important for stability • Sequence stability is not an intrinsic property of genomes because demographic parameters, such as population size and bottleneck size, can have important effects on sequence stability • The multiplicity of cellular infection affects sequence stability, and can in some cases directly affect whether there is selection for deletion variants • Deletions are not the only class of mutations that can reduce the cost of inserted sequences, although they are the most common I: dsDNA

abstract:
  Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.


id: cord-304498-ty41xob0
title: Coronaviruses: An RNA proofreading machine regulates replication fidelity and diversity
author: Denison, Mark R
date: 2011-03-01
txt: ./txt/cord-304498-ty41xob0.txt
cache: ./cache/cord-304498-ty41xob0.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/21593585/
doi: 10.4161/rna.8.2.15013
summary:
  Genetic inactivation of exoN activity in engineered SArS-Cov and MHv genomes by alanine substitution at conserved De-D-D active site residues results in viable mutants that demonstrate 15-to 20-fold increases in mutation rates, up to 18 times greater than those tolerated for fidelity mutants of other rNA viruses. Genetic inactivation of exoN activity in engineered SArS-Cov and MHv genomes by alanine substitution at conserved De-D-D active site residues results in viable mutants that demonstrate 15-to 20-fold increases in mutation rates, up to 18 times greater than those tolerated for fidelity mutants of other rNA viruses. The high mutation rates of RNA viruses also render them particularly susceptible to repeated genetic bottleneck events during replication, transmission between hosts or spread within a host, resulting in progressive deviation from the consensus sequence associated with decreased viral fitness and sometimes extinction.

abstract:
  In order to survive and propagate, RNA viruses must achieve a balance between the capacity for adaptation to new environmental conditions or host cells with the need to maintain an intact and replication competent genome. Several virus families in the order Nidovirales, such as the coronaviruses (CoVs) must achieve these objectives with the largest and most complex replicating RNA genomes known, up to 32 kb of positive-sense RNA. The CoVs encode sixteen nonstructural proteins (nsp 1–16) with known or predicted RNA synthesis and modification activities, and it has been proposed that they are also responsible for the evolution of large genomes. The CoVs, including murine hepatitis virus (MHV) and SARS-CoV, encode a 3′-to-5′ exoribonuclease activity (ExoN) in nsp14. Genetic inactivation of ExoN activity in engineered SARS-CoV and MHV genomes by alanine substitution at conserved DE-D-D active site residues results in viable mutants that demonstrate 15- to 20-fold increases in mutation rates, up to 18 times greater than those tolerated for fidelity mutants of other RNA viruses. Thus nsp14-ExoN is essential for replication fidelity, and likely serves either as a direct mediator or regulator of a more complex RNA proofreading machine, a process previously unprecedented in RNA virus biology. Elucidation of the mechanisms of nsp14-mediated proofreading will have major implications for our understanding of the evolution of RNA viruses, and also will provide a robust model to investigate the balance between fidelity, diversity and pathogenesis. The discovery of a protein distinct from a viral RdRp that regulates replication fidelity also raises the possibility that RNA genome replication fidelity may be adaptable to differing replication environments and selective pressures, rather than being a fixed determinant.


id: cord-304607-td0776wj
title: Omics, Bioinformatics, and Infectious Disease Research
author: Paszkiewicz, Konrad H.
date: 2010-12-24
txt: ./txt/cord-304607-td0776wj.txt
cache: ./cache/cord-304607-td0776wj.txt
extension: .txt
mime: text/plain
url: https://api.elsevier.com/content/article/pii/B9780123848901000182
doi: 10.1016/b978-0-12-384890-1.00018-2
summary:
  This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. Bioinformatics plays a key role at several steps in genomics, comparative genomics, and functional genomics: sequence alignment, assembly, identification of single nucleotide polymorphisms (SNP), gene prediction, quantitative analysis of transcription data, etc. The term "metagenomics" was originally used to describe the sequencing of genomes of uncultured microorganisms in order to explore their abilities to produce natural products (Handelsman et al., 1998 , Rondon et al., 2000 and subsequently resulted in novel insights into the ecology and evolution of microorganisms on a scale not imagined possible before (see Cardenas and Tiedje, 2008; Hugenholtz and Tyson, 2008 for an overview). However, metagenomics now finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms from, for example, patient material that could lead to the identification of the cause of disease.

abstract:
  Bioinformatics is basically the study of informatic processes in biotic systems. Actually what constitutes bioinformatics is not entirely clear and arguably varies depending on who tries to define it. This chapter discusses the considerable progress in infectious diseases research that has been made in recent years using various “omics” case studies. Bioinformatics is tasked with making sense of it, mining it, storing it, disseminating it, and ensuring valid biological conclusions can be drawn from it. This chapter discusses the current state of play of bioinformatics related to genomics and transcriptomics, briefs metagenomics that finds use in infectious disease research as well as the random sequencing of genomes from a variety of organisms. This chapter explains the various possibilities of pan-genome, transcriptional reshaping and also enormous progress of proteomics study. Bioinformatic algorithms and tools are crucial tools in analyzing the data. The chapter also attempts to provide some details on the various problems and solution in bioinformatics that current-day scientists face while concentrating on second-generation sequencing strategies.


id: cord-310406-5pvln91x
author: Asbury, Thomas M
date: 2010-09-02
txt: ./txt/cord-310406-5pvln91x.txt
cache: ./cache/cord-310406-5pvln91x.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/20813045/
doi: 10.1186/1471-2105-11-444
summary:
  RESULTS: We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In addition, in spite of the many recent efforts to measure and model the genome structure at various resolutions and detail [3] [4] [5] [6] [7] [8] [9] [10] , little work has focused on combining these models into a plausible aggregate, or has taken advantage of the large amount of genomic and epigenomic data available from new high-throughput approaches. The viewer is designed to display data from multiple scales and uses a hierarchical model of the relative positions of all nucleotide atoms in the cell nucleus, i.e., the complete physical genome. An integrated physical genome model can show the interplay between histone modifications and other genomic data, such as SNPs, DNA methylation, the structure of gene, promoter and transcription machinery, etc. In addition to epigenomic data, the physical genome model also provides a platform to visualize highthroughput gene expression data and its interplay with global binding information of transcription factors.

title:
  Genome3D: A viewer-model framework for integrating and visualizing multi-scale epigenomic information within a three-dimensional genome

abstract:
  BACKGROUND: New technologies are enabling the measurement of many types of genomic and epigenomic information at scales ranging from the atomic to nuclear. Much of this new data is increasingly structural in nature, and is often difficult to coordinate with other data sets. There is a legitimate need for integrating and visualizing these disparate data sets to reveal structural relationships not apparent when looking at these data in isolation. RESULTS: We have applied object-oriented technology to develop a downloadable visualization tool, Genome3D, for integrating and displaying epigenomic data within a prescribed three-dimensional physical model of the human genome. In order to integrate and visualize large volume of data, novel statistical and mathematical approaches have been developed to reduce the size of the data. To our knowledge, this is the first such tool developed that can visualize human genome in three-dimension. We describe here the major features of Genome3D and discuss our multi-scale data framework using a representative basic physical model. We then demonstrate many of the issues and benefits of multi-resolution data integration. CONCLUSIONS: Genome3D is a software visualization tool that explores a wide range of structural genomic and epigenetic data. Data from various sources of differing scales can be integrated within a hierarchical framework that is easily adapted to new developments concerning the structure of the physical genome. In addition, our tool has a simple annotation mechanism to incorporate non-structural information. Genome3D is unique is its ability to manipulate large amounts of multi-resolution data from diverse sources to uncover complex and new structural relationships within the genome.


id: cord-314594-xvc8hvpq
title: Breeding and biotechnological interventions for trait improvement: status and prospects
author: Singh, Roshan Kumar
date: 2020-09-18
txt: ./txt/cord-314594-xvc8hvpq.txt
cache: ./cache/cord-314594-xvc8hvpq.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32948920/
doi: 10.1007/s00425-020-03465-4
summary:
  Advances in high-throughput genomics strategies at a whole-genome level, including genetic association mapping, map-based cloning, genomic selection, and speed breeding, are also proven useful in improvising genetic gains for expediting the crop improvement processes. Through genome-wide association study (GWAS), 60 loci significantly associated with agronomic traits such as oil content, seed quality, stress tolerance were identified, which may be proven as a valuable resource for genetic improvement (Lu et al. Marker-assisted backcrossing (MABC) is the introgression of a genomic region (QTL or locus or gene) contributing the desired trait from a donor genotype into a breeding line or elite cultivar without linkage drag through backcrossing after multiple generations. As the name suggests, CRISPR/Cas9 consists of two components: a single-guide Application of functional and comparative genomics in marker-assisted breeding and biotechnological approaches for crop improvement. The candidate gene(s) identified from functional genomic studies can be introduced through genetic engineering or tar-geted modify through genome editing technology in crop species for improved agronomic traits.

abstract:
  MAIN CONCLUSION: Present review describes the molecular tools and strategies deployed in the trait discovery and improvement of major crops. The prospects and challenges associated with these approaches are discussed. ABSTRACT: Crop improvement relies on modulating the genes and genomic regions underlying key traits, either directly or indirectly. Direct approaches include overexpression, RNA interference, genome editing, etc., while breeding majorly constitutes the indirect approach. With the advent of latest tools and technologies, these strategies could hasten the improvement of crop species. Next-generation sequencing, high-throughput genotyping, precision editing, use of space technology for accelerated growth, etc. had provided a new dimension to crop improvement programmes that work towards delivering better varieties to cope up with the challenges. Also, studies have widened from understanding the response of plants to single stress to combined stress, which provides insights into the molecular mechanisms regulating tolerance to more than one stress at a given point of time. Altogether, next-generation genetics and genomics had made tremendous progress in delivering improved varieties; however, the scope still exists to expand its horizon to other species that remain underutilized. In this context, the present review systematically analyses the different genomics approaches that are deployed for trait discovery and improvement in major species that could serve as a roadmap for executing similar strategies in other crop species. The application, pros, and cons, and scope for improvement of each approach have been discussed with examples, and altogether, the review provides comprehensive coverage on the advances in genomics to meet the ever-growing demands for agricultural produce. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00425-020-03465-4) contains supplementary material, which is available to authorized users.


id: cord-316033-xg8eb2nm
author: Easton, Alice
date: 2020-11-06
txt: ./txt/cord-316033-xg8eb2nm.txt
cache: ./cache/cord-316033-xg8eb2nm.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/33155980/
doi: 10.7554/elife.61562
summary:
  suum transcripts (Jex et al., 2011; Wang et al., 2017) to the human Ascaris germline assembly to annotate the genome, identifying and classifying 17,902 protein-coding genes ( Table 1 , Supplementary file 1). As this reference-based assembly exhibits the best assembly attributes, including high continuity with a large N50, low gaps and unplaced sequences, and high-quality protein-coding genes (see Table 1 ), we suggest that this version should be used as a reference germline genome for a human Ascaris spp. We next took advantage of the abundant reads from the mitochondrial genome in our sequencing data (on average 7690X coverage, see Supplementary file 1) to perform de novo assembly of 68 complete human Ascaris spp. Furthermore, there were no significant associations between mitochondrial sequence variations and other factors (e.g. village, household, time of worm collection, host) based on PERMANOVA (see methods and Table 2 ) after translating the phylogenetic tree into a distance matrix, suggesting not only a lack of differentiation into distinct species but also a potentially large interbreeding population of worms being transmitted between individuals and across villages.

title:
  Molecular evidence of hybridization between pig and human Ascaris indicates an interbred species complex infecting humans

abstract:
  Human ascariasis is a major neglected tropical disease caused by the nematode Ascaris lumbricoides. We report a 296 megabase (Mb) reference-quality genome comprised of 17,902 protein-coding genes derived from a single, representative Ascaris worm. An additional 68 worms were collected from 60 human hosts in Kenyan villages where pig husbandry is rare. Notably, the majority of these worms (63/68) possessed mitochondrial genomes that clustered closer to the pig parasite Ascaris suum than to A. lumbricoides. Comparative phylogenomic analyses identified over 11 million nuclear-encoded SNPs but just two distinct genetic types that had recombined across the genomes analyzed. The nuclear genomes had extensive heterozygosity, and all samples existed as genetic mosaics with either A. suum-like or A. lumbricoides-like inheritance patterns supporting a highly interbred Ascaris species genetic complex. As no barriers appear to exist for anthroponotic transmission of these ‘hybrid’ worms, a one-health approach to control the spread of human ascariasis will be necessary.


id: cord-318392-r9bbomvk
author: Woo, Patrick CY
date: 2017-06-21
txt: ./txt/cord-318392-r9bbomvk.txt
cache: ./cache/cord-318392-r9bbomvk.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/28634353/
doi: 10.1038/emi.2017.37
summary:
  The genomes of two Coronavirus HKU15 strains detected in the nasopharyngeal samples of two different pigs were sequenced following our previous publications 26, 27 with modifications. Divergence times for the Coronavirus HKU15 strains were calculated based on the complete genome sequence data, utilizing the Bayesian Markov chain Monte Carlo method using BEAST 1.8.0 33 with the substitution model GTR (general time-reversible model)+G (gammadistributed rate variation)+I (estimated proportion of invariable sites), a strict molecular clock, and a constant coalescent. In one (S579N) of the two Coronavirus HKU15 genomes that we sequenced in this study, variant sites were observed at four positions; two of them were due to nucleotide substitutions, and the other two were results of indels at mononucleotide polymeric regions (189th and 376th bases).

title:
  Coronavirus HKU15 in respiratory tract of pigs and first discovery of coronavirus quasispecies in 5′-untranslated region

abstract:
  Coronavirus HKU15 is a deltacoronavirus that was discovered in fecal samples of pigs in Hong Kong in 2012. Over the past three years, Coronavirus HKU15 has been widely detected in pigs in East/Southeast Asia and North America and has been associated with fatal outbreaks. In all such epidemiological studies, the virus was generally only detected in fecal/intestinal samples. In this molecular epidemiology study, we detected Coronavirus HKU15 in 9.6% of the nasopharyngeal samples obtained from 249 pigs in Hong Kong. Samples that tested positive were mostly collected during winter. Complete genome sequencing of the Coronavirus HKU15 in two nasopharyngeal samples revealed quasispecies in one of the samples. Two of the polymorphic sites involved indels, but the other two involved transition substitutions. Phylogenetic analysis showed that the two nasopharyngeal strains in the present study were most closely related to the strains PDCoV/CHJXNI2/2015 from Jiangxi, China, and CH/Sichuan/S27/2012 from Sichuan, China. The outbreak strains in the United States possessed highly similar genome sequences and were clustered monophyletically, whereas the Asian strains were more diverse and paraphyletic. The detection of Coronavirus HKU15 in respiratory tracts of pigs implies that in addition to enteric infections, Coronavirus HKU15 may be able to cause respiratory infections in pigs and that in addition to fecal-oral transmission, the virus could possibly spread through the respiratory route. The presence of the virus in respiratory samples provides an alternative clinical sample to confirm the diagnosis of Coronavirus HKU15 infection. Quasispecies were unprecedentedly observed in the 5′-untranslated region of coronavirus genomes.


id: cord-320005-i30t7cvr
title: The Human Genome and Advances in Medicine: Limits and Future Prospects
author: Pardo, A.
date: 2004-03-31
txt: ./txt/cord-320005-i30t7cvr.txt
cache: ./cache/cord-320005-i30t7cvr.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/S1579212906700787
doi: 10.1016/s1579-2129(06)70078-7
abstract: nan
summary:
  The HGP''s initial objectives were fulfilled 2 years ahead of schedule, and, in addition to compiling a highly accurate sequence of the human genome which has been made freely available and accessible to everyone, the Consortium has developed a set of new technologies and has constructed genetic maps of the genomes of various organisms. Around the same time, the public consortium known as the Human Genome Project was formed, and this organization announced a 15-year plan (from 1990 to 2005) with the following objectives: a) to determine the complete nucleotide sequence of human DNA and identify all the genes in human DNA (estimated to number between 50 000 and 100 000); b) to build physical and genetic maps; c) to analyze the genomes of selected organisms used in research as model systems (eg, the mouse); d) to develop new technologies; and e) to analyze and debate the ethical and legal implications for individuals and for society as a whole.


id: cord-324811-yjwavea5
title: Elucidating genetic diversity with oligonucleotide arrays
author: Kidgell, Claire
date: 2005
txt: ./txt/cord-324811-yjwavea5.txt
cache: ./cache/cord-324811-yjwavea5.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/15868417/
doi: 10.1007/s10577-005-1503-6
summary:
  Oligonucleotide microarrays, predominantly high-density oligonucleotide arrays, have emerged as the principal platforms for performing genome-wide diversity analysis. Since a number of complex issues still remain with high-throughput microarray-based SNP genotyping in humans, in the remainder of this review, we will discuss the application of high-density oligonucleotide arrays to elucidate genetic diversity, with particular focus on studies undertaken with Saccharomyces cerevisiae (Winzeler et al. falciparum (Clark 2002) , the genome-wide analysis facilitated by hybridization of genomic DNA to the A¡ymetrix microarray identi¢ed signi¢cant di¡erences in potential selection pressure across di¡erent gene families and locations within the chromosome (Volkman et al. Although SNPs and deletions can be readily identi¢ed using A¡ymetrix high-density arrays, more complex types of genetic diversity may also be determined using this platform.

abstract:
  DNA microarrays, initially designed to measure gene expression levels, also provide an ideal platform for determining genetic diversity. Oligonucleotide microarrays, predominantly high-density oligonucleotide arrays, have emerged as the principal platforms for performing genome-wide diversity analysis. They have wide-ranging potential applications including comparative genomics, polymorphism discovery and genotyping. The identification of inheritable genetic markers also permits the analysis of quantitative traits, population studies and linkage analysis. In this review, we will discuss the application of oligonucleotide arrays, in particular high-density oligonucleotide arrays for elucidating genetic diversity and highlight some of the directions that the field may take.


id: cord-330312-1pjolkql
title: Infectious Disease Genomics
author: Liu, Y.-T.
date: 2017-01-20
txt: ./txt/cord-330312-1pjolkql.txt
cache: ./cache/cord-330312-1pjolkql.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B978012799942500010X
doi: 10.1016/b978-0-12-799942-5.00010-x
summary:
  One of the important motivations for these efforts is to develop preventative, diagnostic, and therapeutic strategies through the analysis of sequenced microorganisms, parasites, and vectors related to human health. 16, 17 The genomes of human malaria parasite Plasmodium falciparum and its major mosquito vector Anopheles gambiae were published in 2002. 30e32 Genome-sequencing projects for other important human disease vectors are in progress. 38 One of the similar efforts for human pathogens is the NIH Influenza Genome Sequencing Project. 48 The completed or ongoing genome projects (Table 10 .1) provide enormous opportunities for the discovery of novel vaccines and drug targets against human pathogens as well as the improvement of diagnosis and discovery of infectious agents and the development of new strategies for invertebrate vector control. Genome sequence of the human malaria parasite Plasmodium falciparum

abstract:
  The history and development of infectious disease genomics have been closely associated with the Human Genome Project (HGP) during the past 20 years. It has been emphasized since the beginning of the HGP that such effort must not be restricted to the human genome and should include other organisms including mouse, bacteria, yeast, fruit fly, and worm for comparative sequence analyses. A brief history is reviewed in this chapter. As of 2016, more than 7000 completed genome sequencing projects have been reported. One of the important motivations for these efforts is to develop preventative, diagnostic, and therapeutic strategies through the analysis of sequenced microorganisms, parasites, and vectors related to human health. A number of examples are discussed in this chapter.


id: cord-334394-qgyzk7th
title: Petabase-scale sequence alignment catalyses viral discovery
author: Edgar, Robert C.
date: 2020-08-10
txt: ./txt/cord-334394-qgyzk7th.txt
cache: ./cache/cord-334394-qgyzk7th.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.08.07.241729
doi: 10.1101/2020.08.07.241729
summary:
  To address the ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 and expand the known sequence diversity of viruses, we aligned pangenomes for coronaviruses (CoV) and other viral families to 5.6 petabases of public sequencing data from 3.8 million biologically diverse samples. To expand the known repertoire of viruses and catalyse global virus discovery, in particular for Coronaviridae (CoV) family, we developed the Serratus cloud computing architecture for ultra-high throughput sequence alignment. We aligned 3,837,755 public RNA-seq, meta-genome, meta-virome and meta-transcriptome datasets (termed a sequencing run [5] ) against a collection of viral family pangenomes comprising all GenBank CoV records clustered at 99% identity plus all non-retroviral RefSeq records for vertebrate viruses (see Methods and Extended Table 1 ). We performed de novo assembly on 52,772 runs potentially containing CoV sequencing reads by combining 37,131 SRA accessions identified by the Serratus search with 18,584 identified by an ongoing cataloguing initiative of the SRA called STAT [5] .

abstract:
  Public sequence data represents a major opportunity for viral discovery, but its exploration has been inhibited by a lack of efficient methods for searching this corpus, which is currently at the petabase scale and growing exponentially. To address the ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 and expand the known sequence diversity of viruses, we aligned pangenomes for coronaviruses (CoV) and other viral families to 5.6 petabases of public sequencing data from 3.8 million biologically diverse samples. To implement this strategy, we developed a cloud computing architecture, Serratus, tailored for ultra-high throughput sequence alignment at the petabase scale. From this search, we identified and assembled thousands of CoV and CoV-like genomes and genome fragments ranging from known strains to putatively novel genera. We generalise this strategy to other viral families, identifying several novel deltaviruses and huge bacteriophages. To catalyse a new era of viral discovery we made millions of viral alignments and family identifications freely available to the research community. Expanding the known diversity and zoonotic reservoirs of CoV and other emerging pathogens can accelerate vaccine and therapeutic developments for the current pandemic, and help us anticipate and mitigate future ones.


id: cord-340423-f8ab7413
title: Genetic Instability of RNA Viruses
author: Barr, J.N.
date: 2016-09-09
txt: ./txt/cord-340423-f8ab7413.txt
cache: ./cache/cord-340423-f8ab7413.txt
extension: .txt
mime: text/plain
url: https://www.sciencedirect.com/science/article/pii/B9780128033098000021
doi: 10.1016/b978-0-12-803309-8.00002-1
summary:
  We then discuss evidence that at least some RNA viruses have a replication fidelity that is poised to maximize genome sequence space without incurring catastrophic lethal mutations and describe how this can be exploited to control viral infections. The error-prone nature of polymerase activity, coupled with the absence of a proofreading mechanism, is the key reason why RNA virus genomes acquire mutations and exist as a swarm of genetic variants. The mutation rate of the viral polymerase, coupled with the replication mode that the virus employs (and extrinsic factors, described in the following text) will determine the extent of genetic variability of viruses released from an infected cell. Thus, it is possible that the high mutation rates of RNA viruses are simply a consequence of polymerases that are under selective pressure to replicate genomes very rapidly to ensure efficient viral infection [79] [80] [81] .

abstract:
  Despite having very limited coding capacity, RNA viruses are able to withstand challenge of antiviral drugs, cause epidemics in previously exposed human populations, and, in some cases, infect multiple host species. They are able to achieve this by virtue of their ability to multiply very rapidly, coupled with their extraordinary degree of genetic heterogeneity. RNA viruses exist not as single genotypes, but as a swarm of related variants, and this genomic diversity is an essential feature of their biology. RNA viruses have a variety of mechanisms that act in combination to determine their genetic heterogeneity. These include polymerase fidelity, error-mitigation mechanisms, genomic recombination, and different modes of genome replication. RNA viruses can vary in their ability to tolerate mutations, or “genetic robustness,” and several factors contribute to this. Finally, there is evidence that some RNA viruses exist close to a threshold where polymerase error rate has evolved to maximize the possible sequence space available, while avoiding the accumulation of a lethal load of deleterious mutations. We speculate that different viruses have evolved different error rates to complement the different “life-styles” they possess.


id: cord-346335-el45v0a5
title: Fourier spectral density of the coronavirus genome
author: Tan, H.S.
date: 2020-08-11
txt: ./txt/cord-346335-el45v0a5.txt
cache: ./cache/cord-346335-el45v0a5.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1101/2020.06.30.180034
doi: 10.1101/2020.06.30.180034
summary:
  We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density. An example of a seminal paper in this subject is that of Voss in [2] where the author found that the spectral density of the genome of many different species follows a power law of the form 1/k β in the low-frequency domain, with the exponent β potentially related to the organism''s evolutionary category. We develop a few models to characterize the typical spectrum, and in the process stumble upon a linear scaling law between a measure of the complexity of each genome and the power-law exponent that describes the enveloping curve of the low-frequency domain.

abstract:
  We present an analysis of the coronavirus RNA genome via a study of its Fourier spectral density based on a binary representation of the nucleotide sequence. We find that at low frequencies, the power spectrum presents a small and distinct departure from the behavior expected from an uncorrelated sequence. We provide a couple of simple models to characterize such deviations. Away from a small low-frequency domain, the spectrum presents largely stochastic fluctuations about fixed values which vary inversely with the genome size generally. It exhibits no other peaks apart from those associated with triplet codon usage. We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density.


id: cord-348059-wa1gjbck
title: The Human Genome Project changed everything
author: Gibbs, Richard A.
date: 2020-08-07
txt: ./txt/cord-348059-wa1gjbck.txt
cache: ./cache/cord-348059-wa1gjbck.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/32770171/
doi: 10.1038/s41576-020-0275-3
summary:
  Thirty years on from the launch of the Human Genome Project, Richard Gibbs reflects on the promises that this voyage of discovery bore. Thirty years on from the launch of the Human Genome Project, Richard Gibbs reflects on the promises that this voyage of discovery bore. He developed basic methods for DNA and mutation ana lysis and was an early contributor to the Human Genome Project (HGP), leading one of five sites that generated the majority of the sequence. The power of advances in genomics and computers was revealed in the spectacular series of post-HGP projects that were of comparable scale. Some still tally the success of the HGP from lists of new drugs or therapies and argue that world-changing examples in biology, such as the spectacular advances of gene editing tools or the expansion of cancer therapeutics through targeted immunotherapy, are largely based on microbial, cellular and animal studies rather than genomics.

abstract:
  Thirty years on from the launch of the Human Genome Project, Richard Gibbs reflects on the promises that this voyage of discovery bore. Its success should be measured by how this project transformed the rules of research, the way of practising biological discovery and the ubiquitous digitization of biological science.


id: cord-348515-bqqyly23
author: Zhao, Suhui
date: 2014-12-08
txt: ./txt/cord-348515-bqqyly23.txt
cache: ./cache/cord-348515-bqqyly23.txt
extension: .txt
mime: text/plain
url: https://www.ncbi.nlm.nih.gov/pubmed/25482188/
doi: 10.1038/srep07365
summary:
  Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. Thorough characterization of these pathogens is evidenced by the availability of two genome sequences (JF800905 and JX625134), both of which are further identified as the HAdV-7d genome type in this report, and shown to be nearly identical to this report of an isolate from a 2011 ARD outbreak in Guangdong Province (strain DG01_2011) by comparative genomics and, in particular, in silico REA pattern analysis, as presented in Figure 2 .

title:
  Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence

abstract:
  Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed.


id: cord-350747-5t5xthk6
title: Diverse Mechanisms of RNA Recombination
author: Gmyl, A. P.
date: 2005
txt: ./txt/cord-350747-5t5xthk6.txt
cache: ./cache/cord-350747-5t5xthk6.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.1007/s11008-005-0069-x
doi: 10.1007/s11008-005-0069-x
summary:
  It was believed until recently that the only possible mechanism of RNA recombination is replicative template switching, with synthesis of a complementary strand starting on one viral RNA molecule and being completed on another. An illustrative example of deletions is provided by defective interfering (DI) genomes, which accumulate in a virus population upon high-multiplicity infections and lack a fragment of the sequence coding for viral proteins [5] [6] [7] . A special role in the variation of RNA viruses is played by recombination, the generation of new genomes from two or more parental RNAs. Recombination between viral RNA molecules was observed for the first time as early as in the 1960s in the poliovirus [14, 15] . In other words, it is possible to assume that some of the mechanisms of nonreplicative RNA recombination play an important role in the evolution of not only viral, but also cell genomes [51, 90] .

abstract:
  Recombination is widespread among RNA viruses, but many molecular mechanisms of this phenomenon are still poorly understood. It was believed until recently that the only possible mechanism of RNA recombination is replicative template switching, with synthesis of a complementary strand starting on one viral RNA molecule and being completed on another. The newly synthesized RNA is a primary recombinant molecule in this case. Recent studies have revealed other mechanisms of replicative RNA recombination. In addition, recombination between the genomes of RNA viruses can be nonreplicative, resulting from a joining of preexisting parental molecules. Recombination is a potent tool providing for both the variation and conservation of the genome in RNA viruses. Replicative and nonreplicative mechanisms may contribute differently to each of these evolutionary processes. In the form of trans splicing, nonreplicative recombination of cell RNAs plays an important role in at least some organisms. It is conceivable that RNA recombination continues to contribute to the evolution of DNA genomes.


id: cord-352619-s2x53grh
title: Novel Circoviruses Detected in Feces of Sonoran Felids
author: Payne, Natalie
date: 2020-09-15
txt: ./txt/cord-352619-s2x53grh.txt
cache: ./cache/cord-352619-s2x53grh.txt
extension: .txt
mime: text/plain
url: https://doi.org/10.3390/v12091027
doi: 10.3390/v12091027
summary:
  Genomes from several families of circular Rep-encoding single-stranded DNA viruses (CRESS-DNA viruses) are part of the phylum Cressdnaviricota [22] and have been identified in fecal samples of other mammals, including domestic cats [23, 24] , bobcats, African lions [25] , capybaras [26] , and Tasmanian devils [27] . Here we used a metagenomic approach to identify novel circoviruses in the feces of two species of Sonoran felids, the puma and bobcat; although not endangered, knowledge of viral threats facing these species could help prevent future population decline, as well as indicate potential threats to the endangered ocelot and jaguar. Based on the species-demarcation threshold for circoviruses which is 80% genome-wide identity [28] , both of these belong to a new species which we refer to as Sonfela (derived from Sonoran felid associated) circovirus 1. As the viral genomes were derived from scat samples, the circoviruses could have infected the bobcat prey species or the felids themselves or be environmentally derived.

abstract:
  Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids.


