- Title
- Combined burden and functional impact tests for cancer driver discovery using DriverPower
- Creator
- Shuai, Shimin; Abascal, Federico; Carlevaro-Fita, Joana; Chakravarty, Dimple; Chan, Calvin Wing Yiu; Chen, Ken; Choi, Jung Kyoon; Deu-Pons, Jordi; Dhingra, Priyanka; Diamanti, Klev; Feuerbach, Lars; Fink, J. Lynn; Amin, Samirkumar B.; Scarlett, Christopher J.; Frigola, J; Gambacorti-Passerini, C; Garsed, DW; Getz, G; Guo, Q; Gut, IG; Bader, Gary D.; Bandopadhayay, Pratiti; Beroukhim, Rameen; Bertl, Johanna; Boroevich, Keith A.; Brunak, Søren; Campbell, Peter J.
- Relation
- Nature Communications Vol. 11, no. 734
- Publisher Link
- http://dx.doi.org/10.1038/s41467-019-13929-1
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2020
- Description
- 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.
- Subject
- cancer; genomics; mutations; DriverPower; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1500768
- Identifier
- uon:55011
- Identifier
- ISSN:2041-1723
- Rights
- x
- Language
- eng
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