Format

Send to

Choose Destination
Genome Biol. 2016 Dec 16;17(1):261.

A novel independence test for somatic alterations in cancer shows that biology drives mutual exclusivity but chance explains most co-occurrence.

Author information

1
Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands.
2
Department of Medical Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands.
3
Department of Molecular Carcinogenesis, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, 1066 CX, The Netherlands. l.wessels@nki.nl.
4
Faculty of EEMCS, Delft University of Technology, Delft, The Netherlands. l.wessels@nki.nl.
5
Cancer Genomics Netherlands, Amsterdam, The Netherlands. l.wessels@nki.nl.

Abstract

In cancer, mutually exclusive or co-occurring somatic alterations across genes can suggest functional interactions. Existing tests for such patterns make the unrealistic assumption of identical gene alteration probabilities across tumors. We present Discrete Independence Statistic Controlling for Observations with Varying Event Rates (DISCOVER), a novel test that is more sensitive than other methods and controls its false positive rate. A pan-cancer analysis using DISCOVER finds no evidence for widespread co-occurrence, and most co-occurrences previously detected do not exceed expectation by chance. Many mutual exclusivities are identified involving well-known genes related to cell cycle and growth factor signaling, as well as lesser known regulators of Hedgehog signaling.

KEYWORDS:

Co-occurrence; Computational biology; Mutual exclusivity

PMID:
27986087
PMCID:
PMC5162102
DOI:
10.1186/s13059-016-1114-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center