{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T10:48:15Z","timestamp":1774954095741,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1009940","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T00:00:00Z","timestamp":1648425600000}}],"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T00:00:00Z","timestamp":1647388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M008924\/1"],"award-info":[{"award-number":["MR\/M008924\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013589","name":"Research England","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013589","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013589","name":"Research England","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100013589","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000361","name":"Diabetes UK","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000361","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Identifying copy number variants (CNVs) can provide diagnoses to patients and provide important biological insights into human health and disease. Current exome and targeted sequencing approaches cannot detect clinically and biologically-relevant CNVs outside their target area. We present SavvyCNV, a tool which uses off-target read data from exome and targeted sequencing data to call germline CNVs genome-wide. Up to 70% of sequencing reads from exome and targeted sequencing fall outside the targeted regions. We have developed a new tool, SavvyCNV, to exploit this \u2018free data\u2019 to call CNVs across the genome. We benchmarked SavvyCNV against five state-of-the-art CNV callers using truth sets generated from genome sequencing data and Multiplex Ligation-dependent Probe Amplification assays. SavvyCNV called CNVs with high precision and recall, outperforming the five other tools at calling CNVs genome-wide, using off-target or on-target reads from targeted panel and exome sequencing. We then applied SavvyCNV to clinical samples sequenced using a targeted panel and were able to call previously undetected clinically-relevant CNVs, highlighting the utility of this tool within the diagnostic setting. SavvyCNV outperforms existing tools for calling CNVs from off-target reads. It can call CNVs genome-wide from targeted panel and exome data, increasing the utility and diagnostic yield of these tests. SavvyCNV is freely available at\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/github.com\/rdemolgen\/SavvySuite\" xlink:type=\"simple\">https:\/\/github.com\/rdemolgen\/SavvySuite<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1009940","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T13:49:18Z","timestamp":1647438558000},"page":"e1009940","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":32,"title":["SavvyCNV: Genome-wide CNV calling from off-target\u00a0reads"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6399-0089","authenticated-orcid":true,"given":"Thomas W.","family":"Laver","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1437-7891","authenticated-orcid":true,"given":"Elisa","family":"De Franco","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6519-6687","authenticated-orcid":true,"given":"Matthew B.","family":"Johnson","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9240-8104","authenticated-orcid":true,"given":"Kashyap A.","family":"Patel","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7620-5526","authenticated-orcid":true,"given":"Sian","family":"Ellard","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6174-6135","authenticated-orcid":true,"given":"Michael N.","family":"Weedon","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8670-6340","authenticated-orcid":true,"given":"Sarah E.","family":"Flanagan","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6542-9241","authenticated-orcid":true,"given":"Matthew N.","family":"Wakeling","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"pcbi.1009940.ref001","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/0092-8674(94)90137-6","article-title":"The European Polycystic Kidney Disease Consortium (1994) The polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16","volume":"77","journal-title":"Cell"},{"key":"pcbi.1009940.ref002","first-page":"192","article-title":"Localisation of a gene for transient neonatal diabetes mellitus to an 18.72 cR(3000) (~5.4 Mb) interval on chromosome 6q","volume":"36","author":"R. 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