@article{d906b844a2c64162a04f59e1a834cbb6,
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 Bailey, {Matthew H.} 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 Mann, {Graham J.} and Gunnar R{\"a}tsch and Waring, {Paul M.}",
note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",
year = "2020",
month = dec,
day = "1",
doi = "10.1038/s41467-020-18151-y",
language = "English",
volume = "11",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}