| Title: |
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples |
| Authors: |
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; Bieg, M; Boutros, PC; Buchhalter, I; Butler, AP; Chen, K; Chong, Z; Drechsel, O; Jonathan Dursi, L; Eils, R; Espiritu, SMG; Fulton, RS; Gao, S; Gelpi, JLL; Gonzalez, S; Gut, IG; Hach, F; Heinold, MC; Hinton, J; Hu, T; Huang, V; Huang, Y; Hutter, B; Jones, DR; Jung, J; Jäger, N; Kim, HL; Kleinheinz, K; Kumar, S; Kumar, Y; Lalansingh, CM; Letunic, I; Livitz, D; Ma, EZ; Maruvka, YE; Mashl, RJ; Menzies, A; Milovanovic, A; Nielsen, MM; Ossowski, S; Paramasivam, N; Pedersen, JS; Perry, MD; Puiggròs, M; Raine, KM; Rheinbay, E; Royo, R; Sahinalp, SC; Toon, Christopher Chien Wei; Biankin, Andrew; Merrett, Neil; Pinese, Mark; Lau, Loretta; Gill, Anthony; Chou, Angela; Johns, Amber |
| Source: |
urn:ISSN:2041-1723 ; Nature Communications, 11, 1, 4748 |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2020 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
31 Biological Sciences; 32 Biomedical and Clinical Sciences; 3102 Bioinformatics and Computational Biology; 3105 Genetics; 3211 Oncology and Carcinogenesis; Biotechnology; Women's Health; Cancer; Cancer Genomics; Genetics; Human Genome; Precision Medicine; 2.6 Resources and infrastructure (aetiology); 3 Good Health and Well Being; Base Composition; DNA; Intergenic; Databases; Genetic; Exome; Exons; Genome; Human; Humans; Mutation; Neoplasms; Retrospective Studies; Exome Sequencing; Whole Genome Sequencing; MC3 Working Group |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/unsworks_73183 |
| DOI: |
10.1038/s41467-020-18151-y |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_73183; https://unsworks.unsw.edu.au/bitstreams/fe756751-7287-4fd8-a858-fc994c7bfd41/download; https://doi.org/10.1038/s41467-020-18151-y |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY ; https://creativecommons.org/licenses/by/4.0/ ; free_to_read |
| Accession Number: |
edsbas.360FAD67 |
| Database: |
BASE |