Åke Borg
Principal investigator
Combined burden and functional impact tests for cancer driver discovery using DriverPower
Author
Other contributions
- Åke Borg
- Markus Ringnér
- Johan Staaf
Summary, in English
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.
Department/s
- LUCC: Lund University Cancer Centre
- Familial Breast Cancer
- Breastcancer-genetics
- Molecular Cell Biology
- Breast/lungcancer
- Research Group Lung Cancer
Publishing year
2020-02-05
Language
English
Pages
734-734
Publication/Series
Nature Communications
Volume
11
Document type
Journal article
Publisher
Nature Publishing Group
Topic
- Medical Genetics
Keywords
- Algorithms
- Genome, Human
- Genomics/methods
- Humans
- MEF2 Transcription Factors/genetics
- Mutation
- Mutation Rate
- Neoplasms/genetics
- Peptide Elongation Factor 1/genetics
- Receptors, G-Protein-Coupled/genetics
- Software
- Whole Genome Sequencing
Status
Published
Research group
- Familial Breast Cancer
- Research Group Lung Cancer
ISBN/ISSN/Other
- ISSN: 2041-1723