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

Genome Medicine

Mark Pinese¹  Ben Lundie²  Andreas Zankl³  Thomas Ohnesorg⁴  Nicole Schonrock⁴  Marcel E. Dinger⁵  Andre E. Minoche⁶  Sarah Kummerfeld⁶  Mark J. Cowley⁷  Leslie Burnett⁸  Tony Roscioli⁹  David M. Thomas^1,10  Greg B. Peters^1,11 

[1] Children’s Cancer Institute, University of New South Wales, Randwick, Sydney, NSW, Australia;School of Women’s and Children’s Health, UNSW, Sydney, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;Department of Clinical Genetics, The Children’s Hospital at Westmead, Hawkesbury Road, Westmead, NSW, Australia;Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;Genome.One, Darlinghurst, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;School of Biotechnology and Biomolecular Sciences, UNSW, Sydney, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;St Vincent’s Clinical School, UNSW, Sydney, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;St Vincent’s Clinical School, UNSW, Sydney, NSW, Australia;Children’s Cancer Institute, University of New South Wales, Randwick, Sydney, NSW, Australia;School of Women’s and Children’s Health, UNSW, Sydney, NSW, Australia;Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;St Vincent’s Clinical School, UNSW, Sydney, NSW, Australia;Genome.One, Darlinghurst, NSW, Australia;Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia;NSW Health Pathology Randwick, Sydney, NSW, Australia;Centre for Clinical Genetics, Sydney Children’s Hospital, Randwick, NSW, Australia;Prince of Wales Clinical School, University of New South Wales, Sydney, NSW, Australia;Neuroscience Research Australia, University of New South Wales, Randwick, Sydney, NSW, Australia;St Vincent’s Clinical School, UNSW, Sydney, NSW, Australia;The Kinghorn Cancer Centre and Cancer Division, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, NSW, Australia;Sydney Genome Diagnostics, The Children’s Hospital at Westmead, Hawkesbury Road & Hainsworth Street, Westmead, NSW, Australia;

关键词: Structural variation;    Copy number variation;    Whole genome sequencing;    Microarray;    Clinical genome;    Rare disease;   

DOI  :  10.1186/s13073-021-00841-x

来源: Springer

【 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.

【 授权许可】

CC BY