Combined burden and functional impact tests for cancer driver discovery using DriverPower

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  • Shimin Shuai, Ontario Institute for Cancer Research
  • ,
  • PCAWG Drivers and Functional Interpretation Working Group
  • ,
  • Steven Gallinger, University of Toronto, Canada
  • Lincolm Stein, University of Toronto
  • ,
  • PCAWG Consortium

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

OriginalsprogEngelsk
Artikelnummer734
TidsskriftNature Communications
Vol/bind11
Nummer1
Antal sider12
ISSN2041-1723
DOI
StatusUdgivet - 2020

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