TY - JOUR
T1 - Combined burden and functional impact tests for cancer driver discovery using DriverPower
AU - PCAWG Drivers and Functional Interpretation Working Group
AU - PCAWG Consortium
AU - Shuai, Shimin
AU - Abascal, Federico
AU - Amin, Samirkumar B.
AU - Bader, Gary D.
AU - Bandopadhayay, Pratiti
AU - Barenboim, Jonathan
AU - Beroukhim, Rameen
AU - Bertl, Johanna
AU - Boroevich, Keith A.
AU - Brunak, Søren
AU - Campbell, Peter J.
AU - Carlevaro-Fita, Joana
AU - Chakravarty, Dimple
AU - Chan, Calvin Wing Yiu
AU - Chen, Ken
AU - Choi, Jung Kyoon
AU - Deu-Pons, Jordi
AU - Dhingra, Priyanka
AU - Diamanti, Klev
AU - Feuerbach, Lars
AU - Fink, J. Lynn
AU - Fonseca, Nuno A.
AU - Frigola, Joan
AU - Gambacorti-Passerini, Carlo
AU - Garsed, Dale W.
AU - Gerstein, Mark
AU - Getz, Gad
AU - Guo, Qianyun
AU - Gut, Ivo G.
AU - Haan, David
AU - Hamilton, Mark P.
AU - Haradhvala, Nicholas J.
AU - Harmanci, Arif O.
AU - Helmy, Mohamed
AU - Herrmann, Carl
AU - Hess, Julian M.
AU - Hobolth, Asger
AU - Hodzic, Ermin
AU - Hong, Chen
AU - Hornshøj, Henrik
AU - Isaev, Keren
AU - Izarzugaza, Jose M.G.
AU - Johnson, Rory
AU - Johnson, Todd A.
AU - Juul, Malene
AU - Juul, Randi Istrup
AU - Kahles, Andre
AU - Kahraman, Abdullah
AU - Shriver, Craig
AU - Wilkerson, Matthew D.
N1 - Funding Information:
This work was supported in part by the Government of Ontario. We acknowledge the contributions of the many clinical networks across ICGC and TCGA who provided samples and data to the PCAWG Consortium, and the contributions of the Technical Working Group and the Germline Working Group of the PCAWG Consortium for collation, realignment and harmonised variant calling of the cancer genomes used in this study. We thank the patients and their families for their participation in the individual ICGC and TCGA projects.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85079072523&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-13929-1
DO - 10.1038/s41467-019-13929-1
M3 - Article
C2 - 32024818
AN - SCOPUS:85079072523
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 734
ER -