{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T20:53:41Z","timestamp":1754600021421,"version":"3.37.3"},"reference-count":21,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T00:00:00Z","timestamp":1535587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100008552","name":"Brigham Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008552","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01-GM078598","HG007229"],"award-info":[{"award-number":["R01-GM078598","HG007229"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U01HG007690"],"award-info":[{"award-number":["U01HG007690"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000072","name":"National Institute of Dental and Craniofacial Research","doi-asserted-by":"publisher","award":["5U01DE024443"],"award-info":[{"award-number":["5U01DE024443"]}],"id":[{"id":"10.13039\/100000072","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>De novo mutations (i.e. newly occurring mutations) are a pre-dominant cause of sporadic dominant monogenic diseases and play a significant role in the genetics of complex disorders. De novo mutation studies also inform population genetics models and shed light on the biology of DNA replication and repair. Despite the broad interest, there is room for improvement with regard to the accuracy of de novo mutation calling.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We designed novoCaller, a Bayesian variant calling algorithm that uses information from read-level data both in the pedigree and in unrelated samples. The method was extensively tested using large trio-sequencing studies, and it consistently achieved over 97% sensitivity. We applied the algorithm to 48 trio cases of suspected rare Mendelian disorders as part of the Brigham Genomic Medicine gene discovery initiative. Its application resulted in a significant reduction in the resources required for manual inspection and experimental validation of the calls. Three de novo variants were found in known genes associated with rare disorders, leading to rapid genetic diagnosis of the probands. Another 14 variants were found in genes that are likely to explain the phenotype, and could lead to novel disease-gene discovery.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Source code implemented in C++ and Python can be downloaded from https:\/\/github.com\/bgm-cwg\/novoCaller.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty749","type":"journal-article","created":{"date-parts":[[2018,8,30]],"date-time":"2018-08-30T05:23:28Z","timestamp":1535606608000},"page":"1174-1180","source":"Crossref","is-referenced-by-count":6,"title":["novoCaller: a Bayesian network approach for <i>de novo<\/i> variant calling from pedigree and population sequence data"],"prefix":"10.1093","volume":"35","author":[{"given":"Anwoy Kumar","family":"Mohanty","sequence":"first","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}]},{"given":"Dana","family":"Vuzman","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}]},{"given":"Laurent","family":"Francioli","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA"},{"name":"Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA"}]},{"given":"Christopher","family":"Cassa","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}]},{"name":"Brigham Genomic Medicine","sequence":"additional","affiliation":[]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[]},{"name":"Brigham and Women\u2019s Hospital FaceBase Project","sequence":"additional","affiliation":[]},{"given":"Agnes","family":"Toth-Petroczy","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"}]},{"given":"Shamil","family":"Sunyaev","sequence":"additional","affiliation":[{"name":"Division of Genetics, Department of Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA, USA"},{"name":"Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA"}]}],"member":"286","published-online":{"date-parts":[[2018,8,30]]},"reference":[{"key":"2023013107272474500_bty749-B1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.ajhg.2014.08.013","article-title":"De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies","volume":"95","author":"Appenzeller","year":"2014","journal-title":"Am. J. Hum. Genet"},{"key":"2023013107272474500_bty749-B2","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1089\/cmb.2014.0029","article-title":"Joint variant and de novo mutation identification on pedigrees from high-throughput sequencing data","volume":"21","author":"Cleary","year":"2014","journal-title":"J. Comput. Biol"},{"key":"2023013107272474500_bty749-B3","doi-asserted-by":"crossref","first-page":"4667","DOI":"10.1073\/pnas.1221400110","article-title":"Gain-of-function mutations in the mechanically activated ion channel piezo2 cause a subtype of distal arthrogryposis","volume":"110","author":"Coste","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"2023013107272474500_bty749-B4","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/nature21062","article-title":"Prevalence and architecture of de novo mutations in developmental disorders","volume":"542","year":"2017","journal-title":"Nature"},{"key":"2023013107272474500_bty749-B5","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1038\/nature13772","article-title":"Synaptic, transcriptional and chromatin genes disrupted in autism","volume":"515","author":"De Rubeis","year":"2014","journal-title":"Nature"},{"key":"2023013107272474500_bty749-B6","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/ng.3021","article-title":"Whole-genome sequence variation, population structure and demographic history of the dutch population","volume":"46","author":"Francioli","year":"2014","journal-title":"Nat. Genet"},{"key":"2023013107272474500_bty749-B7","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1038\/ng.3292","article-title":"Genome-wide patterns and properties of de novo mutations in humans","volume":"47","author":"Francioli","year":"2015","journal-title":"Nat. Genet"},{"key":"2023013107272474500_bty749-B8","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/ejhg.2016.147","article-title":"A framework for the detection of de novo mutations in family-based sequencing data","volume":"25","author":"Francioli","year":"2017","journal-title":"Eur. J. Hum. Genet"},{"key":"2023013107272474500_bty749-B9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature12929","article-title":"De novo mutations in schizophrenia implicate synaptic networks","volume":"506","author":"Fromer","year":"2014","journal-title":"Nature"},{"key":"2023013107272474500_bty749-B10","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":"2023013107272474500_bty749-B21","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41525-018-0060-9","article-title":"An integrated clinical program and crowdsourcing strategy for genomic sequencing and Mendelian disease gene discovery","volume":"3","author":"Haghighi","year":"2018","journal-title":"NPJ Genom. Med."},{"key":"2023013107272474500_bty749-B11","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1038\/nature13908","article-title":"The contribution of de novo coding mutations to autism spectrum disorder","volume":"515","author":"Iossifov","year":"2014","journal-title":"Nature"},{"key":"2023013107272474500_bty749-B20","first-page":"S","article-title":"Sa2008 - Mutations in Stxbp3 contribute to very early onset of IBD immunodeficieny and hearing loss","volume":"154","author":"Kelsen","year":"2018","journal-title":"Gastroenterology"},{"key":"2023013107272474500_bty749-B12","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature11396","article-title":"Rate of de novo mutations and the importance of fathers age to disease risk","volume":"488","author":"Kong","year":"2012","journal-title":"Nature"},{"volume-title":"Molecular Medicine: An Introduction","year":"2016","author":"Kurreck","key":"2023013107272474500_bty749-B13"},{"key":"2023013107272474500_bty749-B14","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":"2023013107272474500_bty749-B15","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":"2023013107272474500_bty749-B16","doi-asserted-by":"crossref","first-page":"e1003880.","DOI":"10.1371\/journal.pcbi.1003880","article-title":"FamSeq: a variant calling program for family-based sequencing data using graphics processing units","volume":"10","author":"Peng","year":"2014","journal-title":"PLoS Comput. Biol"},{"key":"2023013107272474500_bty749-B17","article-title":"Creating a universal SNP and small indel variant caller with deep neural networks","author":"Poplin","year":"2016","journal-title":"biorxiv"},{"key":"2023013107272474500_bty749-B18","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/nature10945","article-title":"De novo mutations revealed by whole-exome sequencing are strongly associated with autism","volume":"485","author":"Sanders","year":"2012","journal-title":"Nature"},{"key":"2023013107272474500_bty749-B19","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nature12141","article-title":"De novo mutations in histone-modifying genes in congenital heart disease","volume":"498","author":"Zaidi","year":"2013","journal-title":"Nature"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/35\/7\/1174\/48967603\/bioinformatics_35_7_1174.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/35\/7\/1174\/48967603\/bioinformatics_35_7_1174.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,31]],"date-time":"2023-01-31T10:28:15Z","timestamp":1675160895000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/35\/7\/1174\/5087716"}},"subtitle":[],"editor":[{"given":"Oliver","family":"Stegle","sequence":"additional","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2018,8,30]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bty749","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2019,4,1]]},"published":{"date-parts":[[2018,8,30]]}}}