{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:10:43Z","timestamp":1762899043902},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"23","license":[{"start":{"date-parts":[[2016,10,2]],"date-time":"2016-10-02T00:00:00Z","timestamp":1475366400000},"content-version":"vor","delay-in-days":780,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Identifying somatic changes from tumor and matched normal sequences has become a standard approach in cancer research. More specifically, this requires accurate detection of somatic point mutations with low allele frequencies in impure and heterogeneous cancer samples. Although haplotype phasing information derived by using heterozygous germ line variants near candidate mutations would improve accuracy, no somatic mutation caller that uses such information is currently available.<\/jats:p>\n               <jats:p>Results: We propose a Bayesian hierarchical method, termed HapMuC, in which power is increased by using available information on heterozygous germ line variants located near candidate mutations. We first constructed two generative models (the mutation model and the error model). In the generative models, we prepared candidate haplotypes, considering a heterozygous germ line variant if available, and the observed reads were realigned to the haplotypes. We then inferred the haplotype frequencies and computed the marginal likelihoods using a variational Bayesian algorithm. Finally, we derived a Bayes factor for evaluating the possibility of the existence of somatic mutations. We also demonstrated that our algorithm has superior specificity and sensitivity compared with existing methods, as determined based on a simulation, the TCGA Mutation Calling Benchmark 4 datasets and data from the COLO-829 cell line.<\/jats:p>\n               <jats:p>Availability and implementation: The HapMuC source code is available from http:\/\/github.com\/usuyama\/hapmuc.<\/jats:p>\n               <jats:p>Contact: \u00a0imoto@ims.u-tokyo.ac.jp<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu537","type":"journal-article","created":{"date-parts":[[2014,8,15]],"date-time":"2014-08-15T05:12:51Z","timestamp":1408079571000},"page":"3302-3309","source":"Crossref","is-referenced-by-count":19,"title":["HapMuC: somatic mutation calling using heterozygous germ line variants near candidate mutations"],"prefix":"10.1093","volume":"30","author":[{"given":"Naoto","family":"Usuyama","sequence":"first","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Yuichi","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Yusuke","family":"Sato","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"},{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Haruki","family":"Kume","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Yukio","family":"Homma","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Seishi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Satoru","family":"Miyano","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]},{"given":"Seiya","family":"Imoto","sequence":"additional","affiliation":[{"name":"1 Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, 2Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 and 3Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan"}]}],"member":"286","published-online":{"date-parts":[[2014,8,14]]},"reference":[{"key":"2023012712011908100_btu537-B1","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1101\/gr.112326.110","article-title":"Dindel: accurate indel calls from short-read data","volume":"21","author":"Albers","year":"2011","journal-title":"Genome Res."},{"key":"2023012712011908100_btu537-B2","article-title":"Variational Algorithms for Approximate Bayesian Inference","author":"Beal","year":"2003"},{"key":"2023012712011908100_btu537-B3","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/nar\/27.2.573","article-title":"Tandem repeats finder: a program to analyze DNA sequences","volume":"27","author":"Benson","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"2023012712011908100_btu537-B4","first-page":"993","article-title":"Latent dirichlet allocation","volume":"3","author":"Blei","year":"2003","journal-title":"J. Mach. Learn. Res."},{"key":"2023012712011908100_btu537-B5","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1016\/S0031-3203(96)00142-2","article-title":"The use of the area under the ROC curve in the evaluation of machine learning algorithms","volume":"30","author":"Bradley","year":"1997","journal-title":"Pattern Recognit."},{"key":"2023012712011908100_btu537-B6","first-page":"115","article-title":"Scoring pairwise genomic sequence alignments","volume-title":"Pacific Symposium on Biocomputing","author":"Chiaromonte","year":"2002"},{"key":"2023012712011908100_btu537-B7","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1038\/nbt.2514","article-title":"Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples","volume":"31","author":"Cibulskis","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"2023012712011908100_btu537-B8","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1007\/11557067_11","article-title":"On the complexity of several haplotyping problems","volume-title":"Algorithms in Bioinformatics","author":"Cilibrasi","year":"2005"},{"key":"2023012712011908100_btu537-B9","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1038\/nature10738","article-title":"Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing","volume":"481","author":"Ding","year":"2012","journal-title":"Nature"},{"key":"2023012712011908100_btu537-B10","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1093\/bioinformatics\/14.9.755","article-title":"Profile hidden Markov models","volume":"14","author":"Eddy","year":"1998","journal-title":"Bioinformatics"},{"key":"2023012712011908100_btu537-B11","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.patrec.2005.10.010","article-title":"An introduction to ROC analysis","volume":"27","author":"Fawcett","year":"2006","journal-title":"Pattern Recognit. Lett."},{"key":"2023012712011908100_btu537-B12","doi-asserted-by":"crossref","first-page":"D945","DOI":"10.1093\/nar\/gkq929","article-title":"COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer","volume":"39","author":"Forbes","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"2023012712011908100_btu537-B13","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.ajhg.2013.07.002","article-title":"Mapping the human reference genomes missing sequence by three-way admixture in latino genomes","volume":"93","author":"Genovese","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2023012712011908100_btu537-B14","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1109\/TCBB.2008.67","article-title":"Speedhap: an accurate heuristic for the single individual SNP haplotyping problem with many gaps, high reading error rate and low coverage","volume":"5","author":"Genovese","year":"2008","journal-title":"IEEE\/ACM Trans. Comput. Biol. Bioinform."},{"key":"2023012712011908100_btu537-B15","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":"2023012712011908100_btu537-B16","doi-asserted-by":"crossref","first-page":"i183","DOI":"10.1093\/bioinformatics\/btq215","article-title":"Optimal algorithms for haplotype assembly from whole-genome sequence data","volume":"26","author":"He","year":"2010","journal-title":"Bioinformatics"},{"key":"2023012712011908100_btu537-B17","first-page":"656","article-title":"BLAT-the BLAST-like alignment tool","volume":"12","author":"Kent","year":"2002","journal-title":"Genome Res."},{"key":"2023012712011908100_btu537-B18","doi-asserted-by":"crossref","first-page":"11484","DOI":"10.1073\/pnas.1932072100","article-title":"Evolution\u2019s cauldron: duplication, deletion, and rearrangement in the mouse and human genomes","volume":"100","author":"Kent","year":"2003","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012712011908100_btu537-B19","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1101\/gr.129684.111","article-title":"VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing","volume":"22","author":"Koboldt","year":"2012","journal-title":"Genome Res."},{"key":"2023012712011908100_btu537-B20","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1093\/bioinformatics\/btr665","article-title":"SomaticSniper: identification of somatic point mutations in whole genome sequencing data","volume":"28","author":"Larson","year":"2012","journal-title":"Bioinformatics"},{"key":"2023012712011908100_btu537-B21","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/nature07485","article-title":"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome","volume":"456","author":"Ley","year":"2008","journal-title":"Nature"},{"key":"2023012712011908100_btu537-B22","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/nrg2841","article-title":"Advances in understanding cancer genomes through second-generation sequencing","volume":"11","author":"Meyerson","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"2023012712011908100_btu537-B23","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1016\/j.cell.2012.04.023","article-title":"The life history of 21 breast cancers","volume":"149","author":"Nik-Zainal","year":"2012","journal-title":"Cell"},{"key":"2023012712011908100_btu537-B24","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1038\/nature08658","article-title":"A comprehensive catalogue of somatic mutations from a human cancer genome","volume":"463","author":"Pleasance","year":"2010","journal-title":"Nature"},{"key":"2023012712011908100_btu537-B25","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/1471-2105-12-77","article-title":"pROC: an open-source package for R and S+ to analyze and compare ROC curves","volume":"12","author":"Robin","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"2023012712011908100_btu537-B26","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1093\/bioinformatics\/bts053","article-title":"JointSNVMix: a probabilistic model for accurate detection of somatic mutations in normal\/tumour paired next-generation sequencing data","volume":"28","author":"Roth","year":"2012","journal-title":"Bioinformatics"},{"key":"2023012712011908100_btu537-B27","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/ng.2699","article-title":"Integrated molecular analysis of clear-cell renal cell carcinoma","volume":"45","author":"Sato","year":"2013","journal-title":"Nat. Genet."},{"key":"2023012712011908100_btu537-B28","doi-asserted-by":"crossref","first-page":"1811","DOI":"10.1093\/bioinformatics\/bts271","article-title":"Strelka: accurate somatic small-variant calling from sequenced tumor-normal sample pairs","volume":"28","author":"Saunders","year":"2012","journal-title":"Bioinformatics"},{"key":"2023012712011908100_btu537-B29","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1101\/gr.809403","article-title":"Human-mouse alignments with BLASTZ","volume":"13","author":"Schwartz","year":"2003","journal-title":"Genome Res."},{"key":"2023012712011908100_btu537-B30","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":"2023012712011908100_btu537-B31","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":"2023012712011908100_btu537-B32","doi-asserted-by":"crossref","first-page":"e89","DOI":"10.1093\/nar\/gkt126","article-title":"An empirical Bayesian framework for somatic mutation detection from cancer genome sequencing data","volume":"41","author":"Shiraishi","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"2023012712011908100_btu537-B33","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1093\/bib\/bbs017","article-title":"Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration","volume":"14","author":"Thorvaldsd\u00f3ttir","year":"2013","journal-title":"Brief. Bioinform."},{"key":"2023012712011908100_btu537-B34","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature10496","article-title":"Frequent pathway mutations of splicing machinery in myelodysplasia","volume":"478","author":"Yoshida","year":"2011","journal-title":"Nature"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/23\/3302\/48932220\/bioinformatics_30_23_3302.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/23\/3302\/48932220\/bioinformatics_30_23_3302.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T12:58:26Z","timestamp":1674824306000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/30\/23\/3302\/206758"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,14]]},"references-count":34,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2014,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu537","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,12,1]]},"published":{"date-parts":[[2014,8,14]]}}}