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; Sean Kelso; null MC3 Working Group; null PCAWG novel somatic mutation calling methods working group; Gordon Saksena; Kyle Ellrott; Michael C. Wendl; David A. Wheeler; Getz Gad; Jared T. Simpson; Mark B. Gerstein; Li Ding; null PCAWG Consortium; Neil D. Merrett

doi:10.1038/s41467-020-18151-y

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, Sean Kelso, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Gordon Saksena, Kyle Ellrott, Michael C. Wendl, David A. Wheeler, Getz Gad, Jared T. Simpson, Mark B. Gerstein, Li Ding, PCAWG ConsortiumNeil D. Merrett

Western Sydney University

Research output: Contribution to journal › Article › peer-review

32 Citations (Scopus)

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 language	English
Article number	4748
Number of pages	27
Journal	Nature Communications
Volume	11
DOIs	https://doi.org/10.1038/s41467-020-18151-y
Publication status	Published - 2020

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Keywords

cancer
exomes
genomes
mutation (biology)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41467-020-18151-y

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Bailey, M. H., Meyerson, W. U., Dursi, L. J., Wang, L.-B., Dong, G., Liang, W.-W., Weerasinghe, A., Li, S., Kelso, S., MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Saksena, G., Ellrott, K., Wendl, M. C., Wheeler, D. A., Gad, G., Simpson, J. T., Gerstein, M. B., Ding, L., ... Merrett, N. D. (2020). Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nature Communications, 11, Article 4748. https://doi.org/10.1038/s41467-020-18151-y

@article{c9dac4ff0a15433bbc1c7074e3184e4f,

title = "Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples",

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.",

keywords = "cancer, exomes, genomes, mutation (biology)",

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

year = "2020",

doi = "10.1038/s41467-020-18151-y",

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

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Bailey, MH, Meyerson, WU, Dursi, LJ, Wang, L-B, Dong, G, Liang, W-W, Weerasinghe, A, Li, S, Kelso, S, MC3 Working Group, PCAWG novel somatic mutation calling methods working group, Saksena, G, Ellrott, K, Wendl, MC, Wheeler, DA, Gad, G, Simpson, JT, Gerstein, MB, Ding, L, PCAWG Consortium, & Merrett, ND 2020, 'Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples', Nature Communications, vol. 11, 4748. https://doi.org/10.1038/s41467-020-18151-y

TY - JOUR

T1 - Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

AU - Bailey, Matthew H.

AU - Meyerson, William U.

AU - Dursi, Lewis Jonathan

AU - Wang, Liang-Bo

AU - Dong, Guanlan

AU - Liang, Wen-Wei

AU - Weerasinghe, Amila

AU - Li, Shantao

AU - Kelso, Sean

AU - MC3 Working Group, null

AU - PCAWG novel somatic mutation calling methods working group, null

AU - Saksena, Gordon

AU - Ellrott, Kyle

AU - Wendl, Michael C.

AU - Wheeler, David A.

AU - Gad, Getz

AU - Simpson, Jared T.

AU - Gerstein, Mark B.

AU - Ding, Li

AU - PCAWG Consortium, null

AU - Merrett, Neil D.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

KW - cancer

KW - exomes

KW - genomes

KW - mutation (biology)

UR - http://hdl.handle.net/1959.7/uws:57770

U2 - 10.1038/s41467-020-18151-y

DO - 10.1038/s41467-020-18151-y

M3 - Article

SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

M1 - 4748

ER -

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

Abstract

Open Access - Access Right Statement

Keywords

UN SDGs

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