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

Bailey, Matthew H. ; Meyerson, William U. ; Dursi, Lewis Jonathan ; Wang, Liang Bo ; Dong, Guanlan ; Liang, Wen Wei ; Weerasinghe, Amila ; Li, Shantao ; Kelso, Sean and Saksena, Gordon , et al. (2020) In Nature Communications 11(1).
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... (More)

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.

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Nature Communications
volume
11
issue
1
article number
4748
publisher
Nature Publishing Group
external identifiers
  • scopus:85079069163
  • pmid:32958763
ISSN
2041-1723
DOI
10.1038/s41467-020-18151-y
language
English
LU publication?
yes
id
70f79305-f522-4a74-b74b-4d7a566620c6
date added to LUP
2021-01-12 22:47:54
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2024-04-17 23:39:47
@article{70f79305-f522-4a74-b74b-4d7a566620c6,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Bailey, Matthew H. and Meyerson, William U. and Dursi, Lewis Jonathan and Wang, Liang Bo and Dong, Guanlan and Liang, Wen Wei and Weerasinghe, Amila and Li, Shantao and Kelso, Sean and Saksena, Gordon and Ellrott, Kyle and Wendl, Michael C. and Wheeler, David A. and Getz, Gad and Simpson, Jared T. and Gerstein, Mark B. and Ding, Li}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples}},
  url          = {{http://dx.doi.org/10.1038/s41467-020-18151-y}},
  doi          = {{10.1038/s41467-020-18151-y}},
  volume       = {{11}},
  year         = {{2020}},
}