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

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

doi:10.1038/s41467-020-18151-y

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

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

Tutkimustuotos: Artikkeli › Scientific › vertaisarvioitu

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Abstrakti

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.

Alkuperäiskieli	Englanti
Artikkeli	4748
Julkaisu	Nature Communications
Vuosikerta	11
Numero	1
DOI - pysyväislinkit	https://doi.org/10.1038/s41467-020-18151-y
Tila	Julkaistu - 2020
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

Jufo-taso 3

!!ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/s41467-020-18151-yLisenssi: CC BY

retrospective_evaluation_of_2020
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Final published version, 2,35 MBLisenssi: CC BY

http://urn.fi/URN:NBN:fi:tuni-202012078550Lisenssi: CC BY

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MC3 Working Group, PCAWG novel somatic mutation calling methods working group, PCAWG Consortium, Bailey, M. H., Meyerson, W. U., Dursi, L. J., Wang, L. B., Dong, G., Liang, W. W., Weerasinghe, A., Li, S., Kelso, S., Ding, L., Ellrott, K., Getz, G., Saksena, G., Wheeler, D. A., Li, Y., Wendl, M. C., ... Bova, G. S. (2020). Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples. Nature Communications, 11(1), [4748]. https://doi.org/10.1038/s41467-020-18151-y

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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 = "{MC3 Working Group} and {PCAWG novel somatic mutation calling methods working group} and {PCAWG Consortium} and 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 Li Ding and Kyle Ellrott and Gad Getz and Gordon Saksena and Wheeler, {David A.} and Yize Li and Wendl, {Michael C.} and Simpson, {Jared T.} and Gerstein, {Mark B.} and Tapio Visakorpi and Bova, {G. Steven}",

year = "2020",

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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MC3 Working Group, PCAWG novel somatic mutation calling methods working group, PCAWG Consortium, Bailey, MH, Meyerson, WU, Dursi, LJ, Wang, LB, Dong, G, Liang, WW, Weerasinghe, A, Li, S, Kelso, S, Ding, L, Ellrott, K, Getz, G, Saksena, G, Wheeler, DA, Li, Y, Wendl, MC, Simpson, JT, Gerstein, MB, Visakorpi, T & Bova, GS 2020, 'Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples', Nature Communications, Vuosikerta 11, Nro 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 - MC3 Working Group

AU - PCAWG novel somatic mutation calling methods working group

AU - PCAWG Consortium

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 - Ding, Li

AU - Ellrott, Kyle

AU - Getz, Gad

AU - Saksena, Gordon

AU - Wheeler, David A.

AU - Li, Yize

AU - Wendl, Michael C.

AU - Simpson, Jared T.

AU - Gerstein, Mark B.

AU - Visakorpi, Tapio

AU - Bova, G. Steven

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.

U2 - 10.1038/s41467-020-18151-y

DO - 10.1038/s41467-020-18151-y

M3 - Article

C2 - 32958763

AN - SCOPUS:85079069163

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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