{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,22]],"date-time":"2026-03-22T22:57:48Z","timestamp":1774220268246,"version":"3.50.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007660","name":"University of Antwerp","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007660","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Foundation\u2014Flanders","award":["G.0356.17"],"award-info":[{"award-number":["G.0356.17"]}]},{"DOI":"10.13039\/501100002996","name":"Dutch Heart Foundation","doi-asserted-by":"crossref","award":["2013T093"],"award-info":[{"award-number":["2013T093"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010663","name":"European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Research Foundation\u2014Flanders"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Computational identification of copy number variants (CNVs) in sequencing data is a challenging task. Existing CNV-detection methods account for various sources of variation and perform different normalization strategies. However, their applicability and predictions are restricted to specific enrichment protocols. Here, we introduce a novel tool named varAmpliCNV, specifically designed for CNV-detection in amplicon-based targeted resequencing data (Haloplex\u2122 enrichment protocol) in the absence of matched controls. VarAmpliCNV utilizes principal component analysis (PCA) and\/or metric dimensional scaling (MDS) to control variances of amplicon associated read counts enabling effective detection of CNV signals.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Performance of VarAmpliCNV was compared against three existing methods (ConVaDING, ONCOCNV and DECoN) on data of 167 samples run with an aortic aneurysm gene panel (n\u2009=\u200930), including 9 positive control samples. Additionally, we validated the performance on a large deafness gene panel (n\u2009=\u2009145) run on 138 samples, containing 4 positive controls. VarAmpliCNV achieved higher sensitivity (100%) and specificity (99.78%) in comparison to competing methods. In addition, unsupervised clustering of CNV segments and visualization plots of amplicons spanning these regions are included as a downstream strategy to filter out false positives.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>The tool is freely available through galaxy toolshed and at: https:\/\/hub.docker.com\/r\/cmgantwerpen\/varamplicnv. Supplementary Data File S1: https:\/\/tinyurl.com\/2yzswyhh; Supplementary Data File S2: https:\/\/tinyurl.com\/ycyf2fb4.<\/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\/btac756","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T15:53:57Z","timestamp":1669391637000},"source":"Crossref","is-referenced-by-count":4,"title":["varAmpliCNV: analyzing variance of amplicons to detect CNVs in targeted NGS data"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0897-055X","authenticated-orcid":false,"given":"Ajay Anand","family":"Kumar","sequence":"first","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"},{"name":"Biomedical Informatics, Antwerp University Hospital , Antwerp (Wilrijk) 2610, Belgium"},{"name":"Open Targets , Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom"},{"name":"European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI) , Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bart","family":"Loeys","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerarda","family":"Van De Beek","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nils","family":"Peeters","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wim","family":"Wuyts","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lut","family":"Van Laer","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geert","family":"Vandeweyer","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"},{"name":"Biomedical Informatics, Antwerp University Hospital , Antwerp (Wilrijk) 2610, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maaike","family":"Alaerts","sequence":"additional","affiliation":[{"name":"Center of Medical Genetics, University of Antwerp\/Antwerp University Hospital , Antwerp (Edegem) 2650, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"2023010107542049300_btac756-B1","doi-asserted-by":"crossref","first-page":"e158","DOI":"10.1093\/nar\/gku849","article-title":"CnvCapSeq: detecting copy number variation in long-range targeted resequencing data","volume":"42","author":"Bellos","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023010107542049300_btac756-B2","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1093\/nar\/gks001","article-title":"Summarizing and correcting the GC content bias in high-throughput sequencing","volume":"40","author":"Benjamini","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2023010107542049300_btac756-B3","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1093\/bioinformatics\/btu436","article-title":"Multi-factor data normalization enables the detection of copy number aberrations in amplicon sequencing data","volume":"30","author":"Boeva","year":"2014","journal-title":"Bioinformatics"},{"key":"2023010107542049300_btac756-B4","doi-asserted-by":"crossref","first-page":"16031","DOI":"10.1038\/npjgenmed.2016.31","article-title":"The importance of copy number variation in congenital heart disease","volume":"1","author":"Costain","year":"2016","journal-title":"NPJ Genom. 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