{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T22:10:35Z","timestamp":1762899035233},"reference-count":11,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2016,10,3]],"date-time":"2016-10-03T00:00:00Z","timestamp":1475452800000},"content-version":"vor","delay-in-days":845,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: The past several years have seen the development of methodologies to identify genomic variation within a fetus through the non-invasive sequencing of maternal blood plasma. These methods are based on the observation that maternal plasma contains a fraction of DNA (typically 5\u201315%) originating from the fetus, and such methodologies have already been used for the detection of whole-chromosome events (aneuploidies), and to a more limited extent for smaller (typically several megabases long) copy number variants (CNVs).<\/jats:p>\n               <jats:p>Results: Here we present a probabilistic method for non-invasive analysis of de novo CNVs in fetal genome based on maternal plasma sequencing. Our novel method combines three types of information within a unified Hidden Markov Model: the imbalance of allelic ratios at SNP positions, the use of parental genotypes to phase nearby SNPs and depth of coverage to better differentiate between various types of CNVs and improve precision. Our simulation results, based on in silico introduction of novel CNVs into plasma samples with 13% fetal DNA concentration, demonstrate a sensitivity of 90% for CNVs &amp;gt;400 kb (with 13 calls in an unaffected genome), and 40% for 50\u2013400 kb CNVs (with 108 calls in an unaffected genome).<\/jats:p>\n               <jats:p>Availability and implementation: Implementation of our model and data simulation method is available at http:\/\/github.com\/compbio-UofT\/fCNV.<\/jats:p>\n               <jats:p>Contact: \u00a0brudno@cs.toronto.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btu292","type":"journal-article","created":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T21:55:09Z","timestamp":1402955709000},"page":"i212-i218","source":"Crossref","is-referenced-by-count":17,"title":["Probabilistic method for detecting copy number variation in a fetal genome using maternal plasma sequencing"],"prefix":"10.1093","volume":"30","author":[{"given":"Ladislav","family":"Ramp\u00e1\u0161ek","sequence":"first","affiliation":[{"name":"1 Department of Computer Science, University of Toronto, Toronto M5S 2E4, 2Centre for Computational Medicine and 3Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aryan","family":"Arbabi","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Toronto, Toronto M5S 2E4, 2Centre for Computational Medicine and 3Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Brudno","sequence":"additional","affiliation":[{"name":"1 Department of Computer Science, University of Toronto, Toronto M5S 2E4, 2Centre for Computational Medicine and 3Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 1L7, Canada"},{"name":"1 Department of Computer Science, University of Toronto, Toronto M5S 2E4, 2Centre for Computational Medicine and 3Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 1L7, Canada"},{"name":"1 Department of Computer Science, University of Toronto, Toronto M5S 2E4, 2Centre for Computational Medicine and 3Genetics and Genome Biology, Hospital for Sick Children, Toronto M5G 1L7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2014,6,11]]},"reference":[{"key":"2023012711081033300_btu292-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":"2023012711081033300_btu292-B2","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1534\/genetics.113.150029","article-title":"Improving the accuracy and efficiency of identity-by-descent detection in population data","volume":"194","author":"Browning","year":"2013","journal-title":"Genetics"},{"key":"2023012711081033300_btu292-B3","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1002\/pd.4110","article-title":"A method for noninvasive detection of fetal large deletions\/duplications by low coverage massively parallel sequencing","volume":"33","author":"Chen","year":"2013","journal-title":"Prenat. Diagn."},{"key":"2023012711081033300_btu292-B4","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1093\/bioinformatics\/btp156","article-title":"Statistical model for whole genome sequencing and its application to minimally invasive diagnosis of fetal genetic disease","volume":"25","author":"Chu","year":"2009","journal-title":"Bioinformatics"},{"key":"2023012711081033300_btu292-B5","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1016\/S1701-2163(16)32501-4","article-title":"Mid-trimester amniocentesis fetal loss rate","volume":"29","author":"Douglas","year":"2007","journal-title":"J. Obstet. Gynaecol. Can."},{"key":"2023012711081033300_btu292-B6","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nature11251","article-title":"Non-invasive prenatal measurement of the fetal genome","volume":"487","author":"Fan","year":"2012","journal-title":"Nature"},{"key":"2023012711081033300_btu292-B7","doi-asserted-by":"crossref","first-page":"137ra76","DOI":"10.1126\/scitranslmed.3004323","article-title":"Noninvasive whole-genome sequencing of a human fetus","volume":"4","author":"Kitzman","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"2023012711081033300_btu292-B8","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. 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Diagn."}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/12\/i212\/48927182\/bioinformatics_30_12_i212.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/30\/12\/i212\/48927182\/bioinformatics_30_12_i212.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T11:48:02Z","timestamp":1674820082000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/30\/12\/i212\/391732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6,11]]},"references-count":11,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,6,15]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btu292","relation":{},"ISSN":["1367-4811","1367-4803"],"issn-type":[{"value":"1367-4811","type":"electronic"},{"value":"1367-4803","type":"print"}],"subject":[],"published-other":{"date-parts":[[2014,6,15]]},"published":{"date-parts":[[2014,6,11]]}}}