Scalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines.

TitleScalable Open Science Approach for Mutation Calling of Tumor Exomes Using Multiple Genomic Pipelines.
Publication TypeJournal Article
Year of Publication2018
AuthorsEllrott, K, Bailey, MH, Saksena, G, Covington, KR, Kandoth, C, Stewart, C, Hess, J, Ma, S, Chiotti, KE, McLellan, M, Sofia, HJ, Hutter, C, Getz, G, Wheeler, DA, Ding, L
Corporate AuthorsMC3 Working Group, Cancer Genome Atlas Research Network
JournalCell Syst
Volume6
Issue3
Pagination271-281.e7
Date Published2018 03 28
ISSN2405-4712
KeywordsAlgorithms, Exome, Genomics, High-Throughput Nucleotide Sequencing, Humans, Information Dissemination, Mutation, Neoplasms, Sequence Analysis, DNA, Software, Whole Exome Sequencing
Abstract

The Cancer Genome Atlas (TCGA) cancer genomics dataset includes over 10,000 tumor-normal exome pairs across 33 different cancer types, in total >400 TB of raw data files requiring analysis. Here we describe the Multi-Center Mutation Calling in Multiple Cancers project, our effort to generate a comprehensive encyclopedia of somatic mutation calls for the TCGA data to enable robust cross-tumor-type analyses. Our approach accounts for variance and batch effects introduced by the rapid advancement of DNA extraction, hybridization-capture, sequencing, and analysis methods over time. We present best practices for applying an ensemble of seven mutation-calling algorithms with scoring and artifact filtering. The dataset created by this analysis includes 3.5 million somatic variants and forms the basis for PanCan Atlas papers. The results have been made available to the research community along with the methods used to generate them. This project is the result of collaboration from a number of institutes and demonstrates how team science drives extremely large genomics projects.

DOI10.1016/j.cels.2018.03.002
Alternate JournalCell Syst
PubMed ID29596782
PubMed Central IDPMC6075717
Grant ListP30 CA016672 / CA / NCI NIH HHS / United States
U24 CA143882 / CA / NCI NIH HHS / United States
U24 CA143866 / CA / NCI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
U24 CA143840 / CA / NCI NIH HHS / United States
U24 CA143843 / CA / NCI NIH HHS / United States
U24 CA143858 / CA / NCI NIH HHS / United States
U24 CA143848 / CA / NCI NIH HHS / United States
R01 CA180778 / CA / NCI NIH HHS / United States
U24 CA210949 / CA / NCI NIH HHS / United States
R01 CA163722 / CA / NCI NIH HHS / United States
U24 CA143867 / CA / NCI NIH HHS / United States
U24 CA210990 / CA / NCI NIH HHS / United States
U54 HG003067 / HG / NHGRI NIH HHS / United States
U24 CA143835 / CA / NCI NIH HHS / United States
U01 HG006517 / HG / NHGRI NIH HHS / United States
U24 CA210950 / CA / NCI NIH HHS / United States
U24 CA143845 / CA / NCI NIH HHS / United States
U24 CA143799 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
U24 CA144025 / CA / NCI NIH HHS / United States
R01 CA183793 / CA / NCI NIH HHS / United States
HHSN261201400007C / CA / NCI NIH HHS / United States
U24 CA210957 / CA / NCI NIH HHS / United States
U54 HG003079 / HG / NHGRI NIH HHS / United States
U54 HG007990 / HG / NHGRI NIH HHS / United States
U24 CA143883 / CA / NCI NIH HHS / United States
U24 CA211006 / CA / NCI NIH HHS / United States