Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
More about Open Access at the CrickAuthors list
MH Bailey WU Meyerson LJ Dursi LB Wang G Dong WW Liang A Weerasinghe S Li S Kelso MC3 Working Group PCAWG novel somatic mutation calling methods working group G Saksena K Ellrott Michael C Wendl DA Wheeler G Getz Jared T Simpson MB Gerstein L Ding PCAWG ConsortiumAbstract
© 2020, The Author(s). The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
Journal details
Journal Nature Communications
Volume 11
Issue number 1
Pages 4748
Available online
Publication date
Full text links
Publisher website (DOI) 10.1038/s41467-020-18151-y
Figshare View on figshare
Europe PubMed Central 32958763
Pubmed 32958763
Keywords
Related topics
Type of publication