{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T02:38:12Z","timestamp":1784255892959,"version":"3.55.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2015,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Spontaneous (de novo) mutations play an important role in the disease etiology of a range of complex diseases. Identifying de novo mutations (DNMs) in sporadic cases provides an effective strategy to find genes or genomic regions implicated in the genetics of disease. High-throughput next-generation sequencing enables genome- or exome-wide detection of DNMs by sequencing parents-proband trios. It is challenging to sift true mutations through massive amount of noise due to sequencing error and alignment artifacts. One of the critical limitations of existing methods is that for all genomic regions the same pre-specified mutation rate is assumed, which has a significant impact on the DNM calling accuracy.<\/jats:p>\n               <jats:p>Results: In this study, we developed and implemented a novel Bayesian framework for DNM calling in trios (TrioDeNovo), which overcomes these limitations by disentangling prior mutation rates from evaluation of the likelihood of the data so that flexible priors can be adjusted post-hoc at different genomic sites. Through extensively simulations and application to real data we showed that this new method has improved sensitivity and specificity over existing methods, and provides a flexible framework to further improve the efficiency by incorporating proper priors. The accuracy is further improved using effective filtering based on sequence alignment characteristics.<\/jats:p>\n               <jats:p>Availability and implementation: The C++ source code implementing TrioDeNovo is freely available at https:\/\/medschool.vanderbilt.edu\/cgg.<\/jats:p>\n               <jats:p>Contact: \u00a0bingshan.li@vanderbilt.edu<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu839","type":"journal-article","created":{"date-parts":[[2014,12,23]],"date-time":"2014-12-23T03:29:09Z","timestamp":1419305349000},"page":"1375-1381","source":"Crossref","is-referenced-by-count":106,"title":["A Bayesian framework for <i>de novo<\/i> mutation calling in parents-offspring trios"],"prefix":"10.1093","volume":"31","author":[{"given":"Qiang","family":"Wei","sequence":"first","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Zhan","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhong","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhuang","family":"Liu","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujun","family":"Han","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingshan","family":"Li","sequence":"additional","affiliation":[{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"},{"name":"1 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA, 2Quantitative Biomedical Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA, 3Center for Quantitative Sciences, Vanderbilt University, Nashville, TN, USA,4Center for Human Genetic Variation, Duke University, Durham, NC, USA, 5School of Computer Science and Technology, Harbin Institute of Technology, Harbin, China and 6Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,12,21]]},"reference":[{"key":"2023051308510887900_btu839-B1","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/ng.2418","article-title":"Estimating the human mutation rate using autozygosity in a founder population","volume":"44","author":"Campbell","year":"2012","journal-title":"Nat. Genet."},{"key":"2023051308510887900_btu839-B2","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1038\/ng.862","article-title":"Variation in genome-wide mutation rates within and between human families","volume":"43","author":"Conrad","year":"2011","journal-title":"Nat. Genet."},{"key":"2023051308510887900_btu839-B3","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1093\/bioinformatics\/btr330","article-title":"The variant call format and VCFtools","volume":"27","author":"Danecek","year":"2011","journal-title":"Bioinformatics"},{"key":"2023051308510887900_btu839-B4","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"2023051308510887900_btu839-B5","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature12929","article-title":"De\u00a0novo mutations in schizophrenia implicate synaptic networks","volume":"506","author":"Fromer","year":"2014","journal-title":"Nature"},{"key":"2023051308510887900_btu839-B6","doi-asserted-by":"crossref","first-page":"7863","DOI":"10.1073\/pnas.0906232107","article-title":"De\u00a0novo mutations in the gene encoding the synaptic scaffolding protein SHANK3 in patients ascertained for schizophrenia","volume":"107","author":"Gauthier","year":"2010","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023051308510887900_btu839-B7","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ajhg.2013.05.007","article-title":"De\u00a0novo mutations in the genome organizer CTCF cause intellectual disability","volume":"93","author":"Gregor","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"2023051308510887900_btu839-B8","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.cell.2013.06.049","article-title":"Spatial and temporal mapping of de novo mutations in schizophrenia to a fetal prefrontal cortical network","volume":"154","author":"Gulsuner","year":"2013","journal-title":"Cell"},{"key":"2023051308510887900_btu839-B9","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1136\/jmedgenet-2011-100147","article-title":"De\u00a0novo copy number variants associated with intellectual disability have a paternal origin and age bias","volume":"48","author":"Hehir-Kwa","year":"2011","journal-title":"J. Med. Genet."},{"key":"2023051308510887900_btu839-B10","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.neuron.2012.04.009","article-title":"De\u00a0novo gene disruptions in children on the autistic spectrum","volume":"74","author":"Iossifov","year":"2012","journal-title":"Neuron"},{"key":"2023051308510887900_btu839-B11","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.neuron.2011.05.015","article-title":"Rare de novo and transmitted copy-number variation in autistic spectrum disorders","volume":"70","author":"Levy","year":"2011","journal-title":"Neuron"},{"key":"2023051308510887900_btu839-B12","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows\u2013Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023051308510887900_btu839-B13","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":"2023051308510887900_btu839-B14","doi-asserted-by":"crossref","first-page":"e1002944","DOI":"10.1371\/journal.pgen.1002944","article-title":"A likelihood-based framework for variant calling and de novo mutation detection in families","volume":"8","author":"Li","year":"2012","journal-title":"PLoS Genet."},{"key":"2023051308510887900_btu839-B15","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/bioinformatics\/btu141","article-title":"A gradient-boosting approach for filtering de novo mutations in parent-offspring trios","volume":"30","author":"Liu","year":"2014","journal-title":"Bioinformatics"},{"key":"2023051308510887900_btu839-B16","doi-asserted-by":"crossref","first-page":"e17125","DOI":"10.1371\/journal.pone.0017125","article-title":"Ontogenetic de novo copy number variations (CNVs) as a source of genetic individuality: studies on two families with MZD twins for schizophrenia","volume":"6","author":"Maiti","year":"2011","journal-title":"PLoS ONE"},{"key":"2023051308510887900_btu839-B17","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":"2023051308510887900_btu839-B18","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nature11011","article-title":"Patterns and rates of exonic de novo mutations in autism spectrum disorders","volume":"485","author":"Neale","year":"2012","journal-title":"Nature"},{"key":"2023051308510887900_btu839-B19","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nrg2986","article-title":"Genotype and SNP calling from next-generation sequencing data","volume":"12","author":"Nielsen","year":"2011","journal-title":"Nat. Rev. Genet."},{"key":"2023051308510887900_btu839-B20","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/ng.835","article-title":"Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations","volume":"43","author":"O'Roak","year":"2011","journal-title":"Nat. Genet."},{"key":"2023051308510887900_btu839-B21","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nature10989","article-title":"Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations","volume":"485","author":"O'Roak","year":"2012","journal-title":"Nature"},{"key":"2023051308510887900_btu839-B22","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1038\/nmeth.2611","article-title":"DeNovoGear: de novo indel and point mutation discovery and phasing","volume":"10","author":"Ramu","year":"2013","journal-title":"Nat. Methods"},{"key":"2023051308510887900_btu839-B23","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/nrg3585","article-title":"The role of de novo mutations in the genetics of autism spectrum disorders","volume":"15","author":"Ronemus","year":"2014","journal-title":"Nat. Rev. Genet."},{"key":"2023051308510887900_btu839-B24","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature10945","article-title":"De\u00a0novo mutations revealed by whole-exome sequencing are strongly associated with autism","volume":"485","author":"Sanders","year":"2012","journal-title":"Nature"},{"key":"2023051308510887900_btu839-B25","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1126\/science.1138659","article-title":"Strong association of de novo copy number mutations with autism","volume":"316","author":"Sebat","year":"2007","journal-title":"Science"},{"key":"2023051308510887900_btu839-B26","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1038\/ng.712","article-title":"A de novo paradigm for mental retardation","volume":"42","author":"Vissers","year":"2010","journal-title":"Nat. Genet."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/9\/1375\/50306498\/bioinformatics_31_9_1375.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/31\/9\/1375\/50306498\/bioinformatics_31_9_1375.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T08:53:18Z","timestamp":1683967998000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/31\/9\/1375\/200377"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,21]]},"references-count":26,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,5,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu839","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2015,5,1]]},"published":{"date-parts":[[2014,12,21]]}}}