{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T22:24:31Z","timestamp":1769207071321,"version":"3.49.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,4,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: Whole genome sequencing (WGS) of parent-offspring trios is a powerful approach for identifying disease-associated genes via detecting copy number variations (CNVs). Existing approaches, which detect CNVs for each individual in a trio independently, usually yield low-detection accuracy. Joint modeling approaches leveraging Mendelian transmission within the parent-offspring trio can be an efficient strategy to improve CNV detection accuracy.<\/jats:p>\n               <jats:p>Results: In this study, we developed TrioCNV, a novel approach for jointly detecting CNVs in parent-offspring trios from WGS data. Using negative binomial regression, we modeled the read depth signal while considering both GC content bias and mappability bias. Moreover, we incorporated the family relationship and used a hidden Markov model to jointly infer CNVs for three samples of a parent-offspring trio. Through application to both simulated data and a trio from 1000 Genomes Project, we showed that TrioCNV achieved superior performance than existing approaches.<\/jats:p>\n               <jats:p>Availability and implementation: The software TrioCNV implemented using a combination of Java and R is freely available from the website at https:\/\/github.com\/yongzhuang\/TrioCNV.<\/jats:p>\n               <jats:p>Contact: \u00a0ydwang@hit.edu.cn<\/jats:p>\n               <jats:p>Supplementary information: \u00a0Supplementary data are available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btv707","type":"journal-article","created":{"date-parts":[[2015,12,9]],"date-time":"2015-12-09T01:08:44Z","timestamp":1449623324000},"page":"1130-1137","source":"Crossref","is-referenced-by-count":16,"title":["Joint detection of copy number variations in parent-offspring trios"],"prefix":"10.1093","volume":"32","author":[{"given":"Yongzhuang","family":"Liu","sequence":"first","affiliation":[{"name":"1 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Liu","sequence":"additional","affiliation":[{"name":"1 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianguo","family":"Lu","sequence":"additional","affiliation":[{"name":"1 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiajie","family":"Peng","sequence":"additional","affiliation":[{"name":"1 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liran","family":"Juan","sequence":"additional","affiliation":[{"name":"1 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolin","family":"Zhu","sequence":"additional","affiliation":[{"name":"2 Institute for Genomic Medicine, Columbia University, New York, NY 10032,"},{"name":"3 University Program in Genetics and Genomics, Duke University Medical School, Durham, NC 27708,"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingshan","family":"Li","sequence":"additional","affiliation":[{"name":"4 Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37235 and"},{"name":"5 Center for Quantitative Sciences, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yadong","family":"Wang","sequence":"additional","affiliation":[{"name":"1 School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150001, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2015,12,7]]},"reference":[{"key":"2023020112014352900_btv707-B1","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1101\/gr.114876.110","article-title":"CNVnator: an approach to discover, genotype, and characterize typical and atypical CNVs from family and population genome sequencing","volume":"21","author":"Abyzov","year":"2011","journal-title":"Genome Res"},{"key":"2023020112014352900_btv707-B2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nrg2958","article-title":"Genome structural variation discovery and genotyping","volume":"12","author":"Alkan","year":"2011","journal-title":"Nat. Rev.. Genet"},{"key":"2023020112014352900_btv707-B3","doi-asserted-by":"crossref","first-page":"e97","DOI":"10.1093\/nar\/gku345","article-title":"CANOES: detecting rare copy number variants from whole exome sequencing data","volume":"42","author":"Backenroth","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023020112014352900_btv707-B4","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1093\/bioinformatics\/btt198","article-title":"RSVSim: an R\/Bioconductor package for the simulation of structural variations","volume":"29","author":"Bartenhagen","year":"2013","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B5","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"},{"key":"2023020112014352900_btv707-B6","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nmeth.1363","article-title":"BreakDancer: an algorithm for high-resolution mapping of genomic structural variation","volume":"6","author":"Chen","year":"2009","journal-title":"Nat. Methods"},{"key":"2023020112014352900_btv707-B7","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1101\/gr.142455.112","article-title":"Genotype calling and haplotyping in parent-offspring trios","volume":"23","author":"Chen","year":"2013","journal-title":"Genome Res"},{"key":"2023020112014352900_btv707-B8","doi-asserted-by":"crossref","DOI":"10.1186\/1471-2105-14-157","article-title":"Copy number variation genotyping using family information","volume":"14","author":"Chu","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2023020112014352900_btv707-B9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nature07458","article-title":"Copy-number variations associated with neuropsychiatric conditions","volume":"455","author":"Cook","year":"2008","journal-title":"Nature"},{"key":"2023020112014352900_btv707-B10","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":"2023020112014352900_btv707-B11","doi-asserted-by":"crossref","first-page":"e30377","DOI":"10.1371\/journal.pone.0030377","article-title":"Fast computation and applications of genome mappability","volume":"7","author":"Derrien","year":"2012","journal-title":"PLoS One"},{"key":"2023020112014352900_btv707-B12","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/nature13394","article-title":"Genome sequencing identifies major causes of severe intellectual disability","volume":"511","author":"Gilissen","year":"2014","journal-title":"Nature"},{"key":"2023020112014352900_btv707-B13","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1038\/ng.768","article-title":"Discovery and genotyping of genome structural polymorphism by sequencing on a population scale","volume":"43","author":"Handsaker","year":"2011","journal-title":"Nat. Genet"},{"key":"2023020112014352900_btv707-B14","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1101\/gr.120501.111","article-title":"Simultaneous structural variation discovery among multiple paired-end sequenced genomes","volume":"21","author":"Hormozdiari","year":"2011","journal-title":"Genome Res"},{"key":"2023020112014352900_btv707-B15","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/bioinformatics\/btr708","article-title":"ART: a next-generation sequencing read simulator","volume":"28","author":"Huang","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ng.1028","article-title":"De novo assembly and genotyping of variants using colored de Bruijn graphs","volume":"44","author":"Iqbal","year":"2012","journal-title":"Nat. Genet"},{"key":"2023020112014352900_btv707-B17","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1093\/bioinformatics\/btq640","article-title":"The uniqueome: a mappability resource for short-tag sequencing","volume":"27","author":"Koehler","year":"2011","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B18","doi-asserted-by":"crossref","first-page":"R84","DOI":"10.1186\/gb-2014-15-6-r84","article-title":"LUMPY: a probabilistic framework for structural variant discovery","volume":"15","author":"Layer","year":"2014","journal-title":"Genome Biol"},{"key":"2023020112014352900_btv707-B19","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1093\/bioinformatics\/bts330","article-title":"Genomic dark matter: the reliability of short read mapping illustrated by the genome mappability score","volume":"28","author":"Lee","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B20","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":"2023020112014352900_btv707-B21","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":"2023020112014352900_btv707-B22","author":"Li","year":"2013"},{"key":"2023020112014352900_btv707-B23","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B24","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":"2023020112014352900_btv707-B25","doi-asserted-by":"crossref","first-page":"D986","DOI":"10.1093\/nar\/gkt958","article-title":"The database of genomic variants: a curated collection of structural variation in the human genome","volume":"42","author":"MacDonald","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023020112014352900_btv707-B26","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.neuron.2011.11.007","article-title":"High frequencies of de novo CNVs in bipolar disorder and schizophrenia","volume":"72","author":"Malhotra","year":"2011","journal-title":"Neuron"},{"key":"2023020112014352900_btv707-B27","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1093\/biostatistics\/kxt003","article-title":"Quantifying copy number variations using a hidden Markov model with inhomogeneous emission distributions","volume":"14","author":"Mccallum","year":"2013","journal-title":"Biostatistics"},{"key":"2023020112014352900_btv707-B28","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1038\/nmeth.1374","article-title":"Computational methods for discovering structural variation with next-generation sequencing","volume":"6","author":"Medvedev","year":"2009","journal-title":"Nat. Methods"},{"key":"2023020112014352900_btv707-B29","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1038\/nature09708","article-title":"Mapping copy number variation by population-scale genome sequencing","volume":"470","author":"Mills","year":"2011","journal-title":"Nature"},{"key":"2023020112014352900_btv707-B30","doi-asserted-by":"crossref","first-page":"3985","DOI":"10.1073\/pnas.1222158110","article-title":"Rare variant detection using family-based sequencing analysis","volume":"110","author":"Peng","year":"2013","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023020112014352900_btv707-B31","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":"2023020112014352900_btv707-B32","doi-asserted-by":"crossref","first-page":"i333","DOI":"10.1093\/bioinformatics\/bts378","article-title":"DELLY: structural variant discovery by integrated paired-end and split-read analysis","volume":"28","author":"Rausch","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B33","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1038\/ng.3050","article-title":"A framework for the interpretation of de novo mutation in human disease","volume":"46","author":"Samocha","year":"2014","journal-title":"Nat. Genet"},{"key":"2023020112014352900_btv707-B34","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":"2023020112014352900_btv707-B35","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1093\/nar\/gks1363","article-title":"Improving detection of copy-number variation by simultaneous bias correction and read-depth segmentation","volume":"41","author":"Szatkiewicz","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2023020112014352900_btv707-B36","doi-asserted-by":"crossref","first-page":"2711","DOI":"10.1093\/bioinformatics\/bts535","article-title":"Statistical challenges associated with detecting copy number variations with next-generation sequencing","volume":"28","author":"Teo","year":"2012","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B37","doi-asserted-by":"crossref","first-page":"e138","DOI":"10.1093\/nar\/gkn641","article-title":"Modeling genetic inheritance of copy number variations","volume":"36","author":"Wang","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023020112014352900_btv707-B38","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/bioinformatics\/btu839","article-title":"A Bayesian framework for de novo mutation calling in parents-offspring trios","volume":"31","author":"Wei","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B39","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/ng.162","article-title":"Strong association of de novo copy number mutations with sporadic schizophrenia","volume":"40","author":"Xu","year":"2008","journal-title":"Nat. Genet"},{"key":"2023020112014352900_btv707-B40","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.1093\/bioinformatics\/btp394","article-title":"Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads","volume":"25","author":"Ye","year":"2009","journal-title":"Bioinformatics"},{"key":"2023020112014352900_btv707-B41","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/gim.2014.191","article-title":"Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios","volume":"17","author":"Zhu","year":"2015","journal-title":"Genet. Med"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/8\/1130\/49018684\/bioinformatics_32_8_1130.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/32\/8\/1130\/49018684\/bioinformatics_32_8_1130.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,1]],"date-time":"2023-02-01T22:26:06Z","timestamp":1675290366000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/32\/8\/1130\/1743739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,12,7]]},"references-count":41,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,4,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btv707","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2016,4,15]]},"published":{"date-parts":[[2015,12,7]]}}}