{ "name": "bmc-res-notes-vergara-2012", "version": "0.0.0", "keywords": [ "Technical Note" ], "datePublished": "2012-10-31T19:00:00.000Z", "description": "CooVar: Co-occurring variant analyzer", "license": { "url": "http://creativecommons.org/licenses/by/2.0", "name": "open-access", "text": "This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited." }, "author": { "@type": "Person", "givenName": "Ismael A", "familyName": "Vergara", "email": "ivergara@gmail.com", "affiliation": [ { "@type": "Organization", "description": "Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, B.C., V5A 1S6, Canada" }, { "@type": "Organization", "description": "GenomeDx Biosciences Inc, 1595 West 3rd Avenue, Vancouver, BC, V6J 1J8, Canada" } ] }, "contributor": [ { "@type": "Person", "givenName": "Christian", "familyName": "Frech", "email": "frech.christian@gmail.com", "affiliation": [ { "@type": "Organization", "description": "Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, B.C., V5A 1S6, Canada" } ] }, { "@type": "Person", "givenName": "Nansheng", "familyName": "Chen", "email": "chenn@sfu.ca", "affiliation": [ { "@type": "Organization", "description": "Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, B.C., V5A 1S6, Canada" } ] } ], "provider": { "@type": "Organization", "@id": "http://www.ncbi.nlm.nih.gov/pmc/", "description": "From PMC®, a database of the U.S. National Library of Medicine." }, "accountablePerson": { "@type": "Organization", "name": "Standard Analytics IO", "email": "contact@standardanalytics.io" }, "copyrightYear": 2012, "copyrightHolder": { "name": "Vergara et al.; licensee BioMed Central Ltd." }, "dataset": [ { "name": "T1", "alternateName": "Table 1", "description": "Comparison of GVs annotated with CooVar and VEP for human individual HG00732-200-37-ASM", "comment": [ { "@type": "Comment", "text": "Each GV reported by CooVar (v0.05) and VEP (v2.6) was assigned to one (and only one) of the above categories. $ CooVar: Grantham score conservative or moderately conservative; VEP: SIFT benign; + CooVar: Grantham score moderately radical or radical; VEP: SIFT deleterious. * GVs assigned to more than one category due to differential impact on different transcripts. ¥ Presence of internal stop codon within the first 70% of ORF length, after applying all variants. § Predicted frameshift or stop gain variant within the first 70% of ORF length. Abbreviations: GV … genomic variation; ORF … open reading frame; VEP… Variant Effect Predictor; UTR… untranslated region." } ], "distribution": [ { "contentData": "
 CooVarVEP
Runtime
36m
37h 24m
Total reported GVs
4,158,840
4,043,939
 Intronic/intergenic/UTR
4,133,885
4,019,490
 Impacting protein-coding exon
24,955
24,449
  Synonymous/stop retained
11,585
11,434
  Missense
12,011
11,576
   Conservative (%)$
9,526 (79.3)
7,447 (64.3)
   Non-conservative (%)+
2,485 (20.7)
2,110 (18.3)
   Unknown consequence (%)
0 (0)
2,019 (17.4)
  Splice donor/acceptor
97
184
  Stop lost
47
46
  Stop gained
137
134
  Frameshift
470
490
  Inframe
199
165
  Other
0
31
  Multiple*
409
389
ORF disrupted782¥871§
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Note the generally higher density of SNVs towards the telomeres and the presence of chromosome-internal peaks on chromosome IV and V. Data points for this image were automatically generated by CooVar using the --circos option. Circos was then used to generate the image. Circos configuration files necessary to create this type of image are provided with the C. elegans test data set at http://genome.sfu.ca/projects/coovar/.", "thumbnailPath": [ "1756-0500-5-615-1.gif" ], "encoding": [ { "contentPath": "1756-0500-5-615-1.jpg", "encodingFormat": "image/jpeg" } ] }, { "name": "F2", "alternateName": "Figure 2", "caption": "GVs affecting the same protein-coding transcript must be assessed together to correctly predict their functional impact. Panel A shows an example where two neighboring frameshift indels (1-bp insertion and 1-bp deletion, indicated by arrows) cancel each others effect, restoring the original ORF. Panel B shows an example where an otherwise synonymous SNV (G->A, indicated by arrow) causes a missense mutation due to the effect of a neighboring SNV (A->G). In both panels, the first three rows show the reference nucleotide sequence on the forward strand, the reference nucleotide sequence from the reverse strand, and the reference protein sequence translation from the annotated ORF. Note that both ORFs are encoded on the reverse strand, so sequences must be read from right to left. The track below shows the variant sequence detected in human individual HG00732-200-37-ASM, with critical GVs highlighted by arrows. The blue horizontal bar represents the Ensembl protein-coding transcript spanning this genomic region.", "thumbnailPath": [ "1756-0500-5-615-2.gif" ], "encoding": [ { "contentPath": "1756-0500-5-615-2.jpg", "encodingFormat": "image/jpeg" } ] } ], "article": [ { "name": "1756-0500-5-615", "encoding": [ { "contentPath": "1756-0500-5-615.pdf", "encodingFormat": "application/pdf" } ], "@type": "ScholarlyArticle", "publisher": { "@type": "Organization", "name": "BioMed Central" }, "accountablePerson": [ { "@type": "Person", "givenName": "Nansheng", "familyName": "Chen", "email": "chenn@sfu.ca", "affiliation": [ { "@type": "Organization", "description": "Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, B.C., V5A 1S6, Canada" } ] } ], "doi": "10.1186/1756-0500-5-615", "pmid": "23116482", "pmcid": "PMC3532326", "headline": "CooVar: Co-occurring variant analyzer", "abstract": [ { "@type": "Abstract", "hasPart": [ { "@type": "Abstract", "headline": "Background", "abstractBody": "Evaluating the impact of genomic variations (GV) on protein-coding transcripts is an important step in identifying variants of functional significance. Currently available programs for variant annotation depend on external databases or annotate multiple variants affecting the same transcript independently, which limits program use to organisms available in these databases or results in potentially incorrect or incomplete annotations." }, { "@type": "Abstract", "headline": "Findings", "abstractBody": "We have developed CooVar (Co-occurring Variant Analyzer), a database-independent program for assessing the impact of GVs on protein-coding transcripts. CooVar takes GVs, reference genome sequence, and protein-coding exons as input and provides annotated GVs and transcripts as output. Other than similar programs, CooVar considers the combined impact of all GVs affecting the same transcript, generating biologically more accurate annotations. CooVar is operated from the command-line and supports standard file formats VCF, GFF/GTF, and GVF, which makes it easy to integrate into existing computational pipelines. We have extensively tested CooVar on worm and human data sets and demonstrate that it generates correct annotations in only a short amount of time." }, { "@type": "Abstract", "headline": "Conclusions", "abstractBody": "CooVar is an easy-to-use and lightweight variant annotation tool that considers the combined impact of GVs on protein-coding transcripts. CooVar is freely available at http://genome.sfu.ca/projects/coovar/." } ] } ], "isPartOf": { "@type": "PublicationVolume", "volumeNumber": 5, "isPartOf": { "@type": "Periodical", "name": "BMC Research Notes", "alternateName": "BMC Res Notes", "issn": "1756-0500" } }, "pageStart": 615, "pageEnd": 615, "citation": [ { "name": "B1", "doi": "10.1093/hmg/ddq365", "pmid": "20805107", "url": "http://dx.doi.org/10.1093/hmg/ddq365", "sameAs": "http://www.ncbi.nlm.nih.gov/pubmed/20805107", "@type": "ScholarlyArticle", "headline": "Loss-of-function variants in the genomes of healthy humans", "isPartOf": { "@type": "PublicationIssue", "issueNumber": "R2", "isPartOf": { "@type": "PublicationVolume", "volumeNumber": 19, "isPartOf": { "@type": "Periodical", "name": "Hum Mol Genet" } } }, "pageStart": "R125", "pageEnd": "R130", "datePublished": "2009-12-31T19:00:00.000Z", "author": { "@type": "Person", "givenName": "DG", "familyName": "MacArthur" }, "contributor": [ { "@type": "Person", "givenName": 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