{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,3]],"date-time":"2024-08-03T15:38:48Z","timestamp":1722699528378},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"22","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1481,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The invention of next-generation sequencing technology has made it possible to study the rare variants that are more likely to pinpoint causal disease genes. To make such experiments financially viable, DNA samples from several subjects are often pooled before sequencing. This induces large between-pool variation which, together with other sources of experimental error, creates over-dispersed data. Statistical analysis of pooled sequencing data needs to appropriately model this additional variance to avoid inflating the false-positive rate.<\/jats:p>\n               <jats:p>Results: We propose a new statistical method based on an extra-binomial model to address the over-dispersion and apply it to pooled case-control data. We demonstrate that our model provides a better fit to the data than either a standard binomial model or a traditional extra-binomial model proposed by Williams and can analyse both rare and common variants with lower or more variable pool depths compared to the other methods.<\/jats:p>\n               <jats:p>Availability: Package \u2018extraBinomial\u2019 is on http:\/\/cran.r-project.org\/<\/jats:p>\n               <jats:p>Contact: chris.wallace@cimr.cam.ac.uk<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics Online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/bts553","type":"journal-article","created":{"date-parts":[[2012,9,13]],"date-time":"2012-09-13T05:26:11Z","timestamp":1347513971000},"page":"2898-2904","source":"Crossref","is-referenced-by-count":7,"title":["Extra-binomial variation approach for analysis of pooled DNA sequencing data"],"prefix":"10.1093","volume":"28","author":[{"given":"Xin","family":"Yang","sequence":"first","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust\/MRC Building, Addenbrooke\u2019s Hospital, Cambridge CB2 0XY, UK"}]},{"given":"John A.","family":"Todd","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust\/MRC Building, Addenbrooke\u2019s Hospital, Cambridge CB2 0XY, UK"}]},{"given":"David","family":"Clayton","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust\/MRC Building, Addenbrooke\u2019s Hospital, Cambridge CB2 0XY, UK"}]},{"given":"Chris","family":"Wallace","sequence":"additional","affiliation":[{"name":"Juvenile Diabetes Research Foundation\/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust\/MRC Building, Addenbrooke\u2019s Hospital, Cambridge CB2 0XY, UK"}]}],"member":"286","published-online":{"date-parts":[[2012,9,12]]},"reference":[{"key":"2023012513234999800_bts553-B1","doi-asserted-by":"crossref","first-page":"i318","DOI":"10.1093\/bioinformatics\/btq214","article-title":"A statistical method for the detection of variants from next-generation resequencing of DNA pools","volume":"26","author":"Bansal","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012513234999800_bts553-B2","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/ng.381","article-title":"Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes","volume":"41","author":"Barrett","year":"2009","journal-title":"Nat. Genet."},{"key":"2023012513234999800_bts553-B3","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1038\/ng.249","article-title":"Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci","volume":"40","author":"Cooper","year":"2008","journal-title":"Nat. Genet."},{"key":"2023012513234999800_bts553-B4","first-page":"34","article-title":"Beta-binomial ANOVA for proportions","volume":"27","author":"Crowder","year":"1978","journal-title":"J. Roy. Stat. Soc. C"},{"key":"2023012513234999800_bts553-B5","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.csda.2008.01.013","article-title":"The beta-binomial distribution for estimating the number of false rejections in microarray gene expression studies","volume":"53","author":"Hunt","year":"2009","journal-title":"Comput. Stat. Data Anal."},{"key":"2023012513234999800_bts553-B6","doi-asserted-by":"crossref","first-page":"R143","DOI":"10.1186\/gb-2007-8-7-r143","article-title":"Accuracy and quality of massively parallel DNA pyrosequencing","volume":"8","author":"Huse","year":"2007","journal-title":"Genome Biol."},{"key":"2023012513234999800_bts553-B7","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1002\/gepi.20501","article-title":"Design of association studies with pooled or un-pooled next-generation sequencing data","volume":"34","author":"Kim","year":"2010","journal-title":"Genet. Epidemiol."},{"key":"2023012513234999800_bts553-B8","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1093\/bioinformatics\/btp373","article-title":"Varscan: variant detection in massively parallel sequencing of individual and pooled samples","volume":"25","author":"Koboldt","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012513234999800_bts553-B9","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with burrows-wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012513234999800_bts553-B10","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and samtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012513234999800_bts553-B11","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1101\/gr.079558.108","article-title":"Rna-seq: an assessment of technical reproducibility and comparison with gene expression arrays","volume":"18","author":"Marioni","year":"2008","journal-title":"Genome Res."},{"key":"2023012513234999800_bts553-B12","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1214\/aos\/1176346056","article-title":"Quasi-likelihood functions","volume":"11","author":"McCullagh","year":"1983","journal-title":"Ann. Stat."},{"key":"2023012513234999800_bts553-B13","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1126\/science.1167728","article-title":"Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes","volume":"324","author":"Nejentsev","year":"2009","journal-title":"Science"},{"key":"2023012513234999800_bts553-B14","volume-title":"R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing","author":"R Development Core Team","year":"2010"},{"key":"2023012513234999800_bts553-B15","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1038\/ng.952","article-title":"Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease","volume":"43","author":"Rivas","year":"2011","journal-title":"Nat. Genet"},{"key":"2023012513234999800_bts553-B16","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1093\/bioinformatics\/btm453","article-title":"Moderated statistical tests for assessing differences in tag abundance","volume":"23","author":"Robinson","year":"2007","journal-title":"Bioinformatics"},{"key":"2023012513234999800_bts553-B17","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/nmeth.1249","article-title":"Caenorhabditis elegans mutant allele identification by whole-genome sequencing","volume":"5","author":"Sarin","year":"2008","journal-title":"Nat. Methods"},{"key":"2023012513234999800_bts553-B18","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nrg930","article-title":"DNA pooling: a tool for large-scale association studies","volume":"3","author":"Sham","year":"2002","journal-title":"Nat. Rev. Genet."},{"key":"2023012513234999800_bts553-B19","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/nar\/29.1.308","article-title":"dbSNP: the NCBI database of genetic variation","volume":"29","author":"Sherry","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2023012513234999800_bts553-B20","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1038\/ng1800","article-title":"A genome-wide association study of nonsynonymous snps identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region","volume":"38","author":"Smyth","year":"2006","journal-title":"Nat. Genet."},{"key":"2023012513234999800_bts553-B21","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/gepi.20502","article-title":"Resequencing of pooled DNA for detecting disease associations with rare variants","volume":"34","author":"Wang","year":"2010","journal-title":"Genet. Epidemiol."},{"key":"2023012513234999800_bts553-B22","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","article-title":"Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls","volume":"447","author":"Wellcome Trust Case Control Consortium","year":"2007","journal-title":"Nature"},{"key":"2023012513234999800_bts553-B23","first-page":"144","article-title":"Extra-binomial variation in logistic linear models","volume":"31","author":"Williams","year":"1982","journal-title":"J. Roy. Stat. Soc. C (Appl. Stat.)"},{"key":"2023012513234999800_bts553-B24","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1093\/bioinformatics\/btr449","article-title":"A powerful and flexible approach to the analysis of RNA sequence count data","volume":"27","author":"Zhou","year":"2011","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/22\/2898\/48878744\/bioinformatics_28_22_2898.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/22\/2898\/48878744\/bioinformatics_28_22_2898.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T19:21:18Z","timestamp":1674674478000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/22\/2898\/241279"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,9,12]]},"references-count":24,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2012,11,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bts553","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,11,15]]},"published":{"date-parts":[[2012,9,12]]}}}