{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T01:03:26Z","timestamp":1773277406366,"version":"3.50.1"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":1785,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/3.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,1,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The study of cancer genomes now routinely involves using next-generation sequencing technology (NGS) to profile tumours for single nucleotide variant (SNV) somatic mutations. However, surprisingly few published bioinformatics methods exist for the specific purpose of identifying somatic mutations from NGS data and existing tools are often inaccurate, yielding intolerably high false prediction rates. As such, the computational problem of accurately inferring somatic mutations from paired tumour\/normal NGS data remains an unsolved challenge.<\/jats:p>\n               <jats:p>Results: We present the comparison of four standard supervised machine learning algorithms for the purpose of somatic SNV prediction in tumour\/normal NGS experiments. To evaluate these approaches (random forest, Bayesian additive regression tree, support vector machine and logistic regression), we constructed 106 features representing 3369 candidate somatic SNVs from 48 breast cancer genomes, originally predicted with naive methods and subsequently revalidated to establish ground truth labels. We trained the classifiers on this data (consisting of 1015 true somatic mutations and 2354 non-somatic mutation positions) and conducted a rigorous evaluation of these methods using a cross-validation framework and hold-out test NGS data from both exome capture and whole genome shotgun platforms. All learning algorithms employing predictive discriminative approaches with feature selection improved the predictive accuracy over standard approaches by statistically significant margins. In addition, using unsupervised clustering of the ground truth \u2018false positive\u2019 predictions, we noted several distinct classes and present evidence suggesting non-overlapping sources of technical artefacts illuminating important directions for future study.<\/jats:p>\n               <jats:p>Availability: Software called MutationSeq and datasets are available from http:\/\/compbio.bccrc.ca.<\/jats:p>\n               <jats:p>Contact: \u00a0saparicio@bccrc.ca<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btr629","type":"journal-article","created":{"date-parts":[[2011,11,15]],"date-time":"2011-11-15T15:18:21Z","timestamp":1321370301000},"page":"167-175","source":"Crossref","is-referenced-by-count":130,"title":["Feature-based classifiers for somatic mutation detection in tumour\u2013normal paired sequencing data"],"prefix":"10.1093","volume":"28","author":[{"given":"Jiarui","family":"Ding","sequence":"first","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"},{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Bashashati","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Roth","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arusha","family":"Oloumi","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kane","family":"Tse","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Zeng","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gholamreza","family":"Haffari","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Hirst","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco A.","family":"Marra","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Condon","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Aparicio","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"},{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohrab P.","family":"Shah","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"},{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"},{"name":"1 Department of Molecular Oncology, BC Cancer Agency, 2Department of Computer Science, University of British Columbia, 3Canada's Michael Smith Genome Science Centre and 4Department of Pathology, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2011,11,13]]},"reference":[{"key":"2023012511345181800_B1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1093\/bioinformatics\/btp630","article-title":"Robust biomarker identification for cancer diagnosis with ensemble feature selection methods","volume":"26","author":"Abeel","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012511345181800_B2","doi-asserted-by":"crossref","first-page":"i77","DOI":"10.1093\/bioinformatics\/btr205","article-title":"vipR: variant identification in pooled DNA using R","volume":"27","author":"Altmann","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012511345181800_B3","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1093\/bioinformatics\/btr174","article-title":"Bamtools: a C++ API and toolkit for analyzing and managing BAM files","volume":"27","author":"Barnett","year":"2011","journal-title":"Bioinformatics"},{"key":"2023012511345181800_B4","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nature09837","article-title":"Initial genome sequencing and analysis of multiple myeloma","volume":"471","author":"Chapman","year":"2011","journal-title":"Nature"},{"key":"2023012511345181800_B5","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1214\/09-AOAS285","article-title":"BART: Bayesian additive regression trees","volume":"4","author":"Chipman","year":"2010","journal-title":"Ann. Appl. Stat."},{"key":"2023012511345181800_B6","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1038\/nature08989","article-title":"Genome remodelling in a basal-like breast cancer metastasis and xenograft","volume":"464","author":"Ding","year":"2010","journal-title":"Nature"},{"key":"2023012511345181800_B7","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1093\/bioinformatics\/btq040","article-title":"SNVMix: predicting single nucleotide variants from next-generation sequencing of tumors","volume":"26","author":"Goya","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012511345181800_B8","first-page":"320","article-title":"Algorithm as 217: computation of the dip statistic to test for unimodality","volume":"34","author":"Hartigan","year":"1985","journal-title":"J. R. Stat. Soc. Ser. C"},{"key":"2023012511345181800_B9","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-84858-7","volume-title":"The Elements of Statistical Learning: Data Mining, Inference, and Prediction.","author":"Hastie","year":"2009"},{"key":"2023012511345181800_B10","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":"2023012511345181800_B11","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":"2023012511345181800_B12","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1101\/gr.088013.108","article-title":"SNP detection for massively parallel whole-genome resequencing","volume":"19","author":"Li","year":"2009","journal-title":"Genome Res."},{"key":"2023012511345181800_B13","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/path.2848","article-title":"Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas","volume":"223","author":"McConechy","year":"2011","journal-title":"J. Pathol."},{"key":"2023012511345181800_B14","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"2023012511345181800_B15","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1186\/1471-2105-12-451","article-title":"Identification and correction of systematic error in highthroughput sequence data","volume":"12","author":"Meacham","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023012511345181800_B16","doi-asserted-by":"crossref","DOI":"10.1038\/npre.2011.5989.1","article-title":"Identification and correction of systematic error in highthroughput sequence data","author":"Meacham","year":"2011","journal-title":"Nature Precedings"},{"key":"2023012511345181800_B17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/ng.518","article-title":"Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin","volume":"42","author":"Morin","year":"2010","journal-title":"Nat. Genet."},{"key":"2023012511345181800_B18","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10351","article-title":"Frequent mutation of histone-modifying genes in non-hodgkin lymphoma","volume":"476","author":"Morin","year":"2011","journal-title":"Nature"},{"key":"2023012511345181800_B19","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature10113","article-title":"Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia","volume":"475","author":"Puente","year":"2011","journal-title":"Nature"},{"key":"2023012511345181800_B20","doi-asserted-by":"crossref","first-page":"2719","DOI":"10.1056\/NEJMoa0902542","article-title":"Mutation of FOXL2 in granulosa-cell tumors of the ovary","volume":"360","author":"Shah","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"2023012511345181800_B21","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1038\/nature08489","article-title":"Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution","volume":"461","author":"Shah","year":"2009","journal-title":"Nature"},{"key":"2023012511345181800_B22","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/nature09639","article-title":"Exome sequencing identifies frequent mutation of the SWI\/SNF complex gene PBRM1 in renal carcinoma","volume":"469","author":"Varela","year":"2011","journal-title":"Nature"},{"key":"2023012511345181800_B23","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1056\/NEJMoa1008433","article-title":"ARID1A mutations in endometriosis-associated ovarian carcinomas","volume":"363","author":"Wiegand","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2023012511345181800_B24","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1056\/NEJMoa0808710","article-title":"IDH1 and IDH2 mutations in gliomas","volume":"360","author":"Yan","year":"2009","journal-title":"N. Engl. J. Med."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/2\/167\/48869226\/bioinformatics_28_2_167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/28\/2\/167\/48869226\/bioinformatics_28_2_167.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T11:39:13Z","timestamp":1674646753000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/28\/2\/167\/197256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11,13]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,1,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btr629","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2012,1,15]]},"published":{"date-parts":[[2011,11,13]]}}}