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;
D O I：
暂无
中图分类号：
学科分类号：
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.
引用
收藏
相关论文
共 275 条
  • [21] van de Vorst M(2015)svviz: a read viewer for validating structural variants Bioinformatics. 31 3994-443
  • [22] van Bon BWM(2017)SVPV: a structural variant prediction viewer for paired-end sequencing datasets Bioinformatics. 33 2032-65
  • [23] Willemsen MH(2014)The database of genomic variants: a curated collection of structural variation in the human genome Nucleic Acids Res 42 D986-14
  • [24] Miller DT(2020)The mutational constraint spectrum quantified from variation in 141,456 humans Nature 581 434-2207
  • [25] Adam MP(2011)Mapping copy number variation by population-scale genome sequencing Nature. 470 59-1007
  • [26] Aradhya S(2016)svclassify: a method to establish benchmark structural variant calls BMC Genomics 17 64-D716
  • [27] Biesecker LG(2016)Clinical detection of deletion structural variants in whole-genome sequences NPJ Genomic Med 1 16026-594
  • [28] Brothman AR(2020)The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly Nat Commun 11 1-611
  • [29] Carter NP(2010)BigWig and BigBed: enabling browsing of large distributed datasets Bioinformatics. 26 2204-468
  • [30] Telenti A(2002)Recent segmental duplications in the human genome Science. 297 1003-580
12345678910