ClinSV: clinical grade structural and copy number variant detection from whole genome sequencing data

被引:0
作者
Andre E. Minoche
Ben Lundie
Greg B. Peters
Thomas Ohnesorg
Mark Pinese
David M. Thomas
Andreas Zankl
Tony Roscioli
Nicole Schonrock
Sarah Kummerfeld
Leslie Burnett
Marcel E. Dinger
Mark J. Cowley
机构
[1] Kinghorn Centre for Clinical Genomics,Children’s Cancer Institute
[2] Garvan Institute of Medical Research,Sydney Medical School
[3] St Vincent’s Clinical School,Prince of Wales Clinical School
[4] Sydney Genome Diagnostics,Neuroscience Research Australia
[5] The Children’s Hospital at Westmead,undefined
[6] Genome.One,undefined
[7] University of New South Wales,undefined
[8] School of Women’s and Children’s Health,undefined
[9] The Kinghorn Cancer Centre and Cancer Division,undefined
[10] Garvan Institute of Medical Research,undefined
[11] Department of Clinical Genetics,undefined
[12] The Children’s Hospital at Westmead,undefined
[13] The University of Sydney,undefined
[14] NSW Health Pathology Randwick,undefined
[15] Centre for Clinical Genetics,undefined
[16] Sydney Children’s Hospital,undefined
[17] University of New South Wales,undefined
[18] University of New South Wales,undefined
[19] School of Biotechnology and Biomolecular Sciences,undefined
来源
Genome Medicine | / 13卷
关键词
Structural variation; Copy number variation; Whole genome sequencing; Microarray; Clinical genome; Rare disease;
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摘要
Whole genome sequencing (WGS) has the potential to outperform clinical microarrays for the detection of structural variants (SV) including copy number variants (CNVs), but has been challenged by high false positive rates. Here we present ClinSV, a WGS based SV integration, annotation, prioritization, and visualization framework, which identified 99.8% of simulated pathogenic ClinVar CNVs > 10 kb and 11/11 pathogenic variants from matched microarrays. The false positive rate was low (1.5–4.5%) and reproducibility high (95–99%). In clinical practice, ClinSV identified reportable variants in 22 of 485 patients (4.7%) of which 35–63% were not detectable by current clinical microarray designs. ClinSV is available at https://github.com/KCCG/ClinSV.
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