Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Matthew H. Bailey, William U. Meyerson, Lewis Jonathan Dursi, Liang-Bo Wang, Guanlan Dong, Wen-Wei Liang, Amila Weerasinghe, Shantao Li, Yize Li, Sean Kelso, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Gordon Saksena, Kyle Ellrott, Michael C. Wendl, David A. Wheeler, Gad Getz, Jared T. Simpson, Mark B. Gerstein, Li DingPCAWG Consortium

    Research output: Contribution to journalArticlepeer-review

    32 Citations (Scopus)
    61 Downloads (Pure)

    Abstract

    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.

    Original languageEnglish
    Article number4748
    Pages (from-to)1-27
    Number of pages27
    JournalNature Communications
    Volume11
    Issue number1
    DOIs
    Publication statusPublished - 21 Sept 2020

    Bibliographical note

    Copyright the Author(s) 2020. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

    Fingerprint

    Dive into the research topics of 'Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples'. Together they form a unique fingerprint.

    Cite this