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; Rehan Akbani; Pavana Anur; Alex Buchanan; Kami Chiotti; Kyle Covington; Allison Creason; Li Ding; Kyle Ellrott; Yu Fan; Steven Foltz; Gad Getz; Walker Hale; David Haussler; Julian M. Hess; Carolyn M. Hutter; Cyriac Kandoth; Katayoon Kasaian; Melpomeni Kasapi; Dave Larson; Ignaty Leshchiner; John Letaw; Singer Ma; Michael D. McLellan; Yifei Men; Gordon B. Mills; Beifang Niu; Myron Peto; Amie Radenbaugh; Sheila M. Reynolds; Gordon Saksena; Heidi Sofia; Chip Stewart; Adam J. Struck; Joshua M. Stuart; Wenyi Wang; John N. Weinstein; David A. Wheeler; Christopher K. Wong; Liu Xi; Kai Ye; MC3 Working Group; PCAWG Consortium; PCAWG novel somatic mutation calling methods working group; David Townend; Mark Gerstein; L. Ding

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, Rehan Akbani, Pavana Anur, Alex Buchanan, Kami Chiotti, Kyle Covington, Allison Creason, Li Ding^*, Kyle Ellrott, Yu Fan, Steven Foltz, Gad GetzWalker Hale, David Haussler, Julian M. Hess, Carolyn M. Hutter, Cyriac Kandoth, Katayoon Kasaian, Melpomeni Kasapi, Dave Larson, Ignaty Leshchiner, John Letaw, Singer Ma^*, Michael D. McLellan, Yifei Men, Gordon B. Mills, Beifang Niu, Myron Peto, Amie Radenbaugh, Sheila M. Reynolds, Gordon Saksena, Heidi Sofia, Chip Stewart, Adam J. Struck, Joshua M. Stuart, Wenyi Wang, John N. Weinstein, David A. Wheeler, Christopher K. Wong, Liu Xi, Kai Ye, MC3 Working Group, PCAWG Consortium, PCAWG novel somatic mutation calling methods working group, David Townend, Mark Gerstein^*, L. Ding^*

^*Corresponding author for this work

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

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
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-18151-y
Publication status	Published - 21 Sept 2020

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1 Erratum / corrigendum / retractions

Author Correction: Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Bailey, M. H., Meyerson, W. U., Dursi, L. J., Wang, L. B., Dong, G., Liang, W. W., Weerasinghe, A., Li, S., Li, Y., Kelso, S., Akbani, R., Anur, P., Buchanan, A., Chiotti, K., Covington, K., Creason, A., Ding, L., Ellrott, K., Fan, Y. & Foltz, S. & 34 others, Getz, G., Hale, W., Haussler, D., Hess, J. M., Hutter, C. M., Kandoth, C., Kasaian, K., Kasapi, M., Larson, D., Leshchiner, I., Letaw, J., Ma, S., McLellan, M. D., Men, Y., Mills, G. B., Niu, B., Peto, M., Radenbaugh, A., Reynolds, S. M., Saksena, G., Sofia, H., Stewart, C., Struck, A. J., Stuart, J. M., Wang, W., Weinstein, J. N., Wheeler, D. A., Wong, C. K., Xi, L., MC3 Working Group, PCAWG Consortium, PCAWG novel somatic mutation calling methods working group, Townend, D. & Gerstein, M., 1 Dec 2020, In: Nature Communications. 11, 1, 1 p., 6232.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

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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., Akbani, R., Anur, P., Buchanan, A., Chiotti, K., Covington, K., Creason, A., Ding, L., Ellrott, K., Fan, Y., Foltz, S., ... Ding, L. (2020). Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nature Communications, 11(1), Article 4748. https://doi.org/10.1038/s41467-020-18151-y

@article{5d14c34fd3a443d591c0a6c97ae51a05,

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.",

author = "Bailey, {Matthew H.} and Meyerson, {William U.} and Dursi, {Lewis Jonathan} and Wang, {Liang Bo} and Guanlan Dong and Liang, {Wen Wei} and Amila Weerasinghe and Shantao Li and Sean Kelso and Rehan Akbani and Pavana Anur and Alex Buchanan and Kami Chiotti and Kyle Covington and Allison Creason and Li Ding and Kyle Ellrott and Yu Fan and Steven Foltz and Gad Getz and Walker Hale and David Haussler and Hess, {Julian M.} and Hutter, {Carolyn M.} and Cyriac Kandoth and Katayoon Kasaian and Melpomeni Kasapi and Dave Larson and Ignaty Leshchiner and John Letaw and Singer Ma and McLellan, {Michael D.} and Yifei Men and Mills, {Gordon B.} and Beifang Niu and Myron Peto and Amie Radenbaugh and Reynolds, {Sheila M.} and Gordon Saksena and Heidi Sofia and Chip Stewart and Struck, {Adam J.} and Stuart, {Joshua M.} and Wenyi Wang and Weinstein, {John N.} and Wheeler, {David A.} and Wong, {Christopher K.} and Liu Xi and Kai Ye and {MC3 Working Group} and {PCAWG Consortium} and {PCAWG novel somatic mutation calling methods working group} and David Townend and Mark Gerstein and L. Ding",

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = sep,

day = "21",

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

language = "English",

volume = "11",

journal = "Nature Communications",

issn = "2041-1723",

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number = "1",

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Bailey, MH, Meyerson, WU, Dursi, LJ, Wang, LB, Dong, G, Liang, WW, Weerasinghe, A, Li, S, Kelso, S, Akbani, R, Anur, P, Buchanan, A, Chiotti, K, Covington, K, Creason, A, Ding, L, Ellrott, K, Fan, Y, Foltz, S, Getz, G, Hale, W, Haussler, D, Hess, JM, Hutter, CM, Kandoth, C, Kasaian, K, Kasapi, M, Larson, D, Leshchiner, I, Letaw, J, Ma, S, McLellan, MD, Men, Y, Mills, GB, Niu, B, Peto, M, Radenbaugh, A, Reynolds, SM, Saksena, G, Sofia, H, Stewart, C, Struck, AJ, Stuart, JM, Wang, W, Weinstein, JN, Wheeler, DA, Wong, CK, Xi, L, Ye, K, MC3 Working Group, PCAWG Consortium, PCAWG novel somatic mutation calling methods working group, Townend, D, Gerstein, M & Ding, L 2020, 'Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples', Nature Communications, vol. 11, no. 1, 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 - Akbani, Rehan

AU - Anur, Pavana

AU - Buchanan, Alex

AU - Chiotti, Kami

AU - Covington, Kyle

AU - Creason, Allison

AU - Ding, Li

AU - Ellrott, Kyle

AU - Fan, Yu

AU - Foltz, Steven

AU - Getz, Gad

AU - Hale, Walker

AU - Haussler, David

AU - Hess, Julian M.

AU - Hutter, Carolyn M.

AU - Kandoth, Cyriac

AU - Kasaian, Katayoon

AU - Kasapi, Melpomeni

AU - Larson, Dave

AU - Leshchiner, Ignaty

AU - Letaw, John

AU - Ma, Singer

AU - McLellan, Michael D.

AU - Men, Yifei

AU - Mills, Gordon B.

AU - Niu, Beifang

AU - Peto, Myron

AU - Radenbaugh, Amie

AU - Reynolds, Sheila M.

AU - Saksena, Gordon

AU - Sofia, Heidi

AU - Stewart, Chip

AU - Struck, Adam J.

AU - Stuart, Joshua M.

AU - Wang, Wenyi

AU - Weinstein, John N.

AU - Wheeler, David A.

AU - Wong, Christopher K.

AU - Xi, Liu

AU - Ye, Kai

AU - MC3 Working Group

AU - PCAWG Consortium

AU - PCAWG novel somatic mutation calling methods working group

AU - Townend, David

AU - Gerstein, Mark

AU - Ding, L.

PY - 2020/9/21

Y1 - 2020/9/21

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.

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

IS - 1

M1 - 4748

ER -

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

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

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