DriverGroup: a novel method for identifying driver gene groups

Author:

Pham Vu V H1,Liu Lin1,Bracken Cameron P23,Goodall Gregory J23,Li Jiuyong1,Le Thuc D1ORCID

Affiliation:

1. UniSA STEM, University of South Australia, Mawson Lakes, SA, 5095, Australia

2. Centre for Cancer Biology, an alliance of SA Pathology and University of South Australia, Adelaide, SA, 5000, Australia

3. Department of Medicine, The University of Adelaide, Adelaide, SA 5005, Australia

Abstract

Abstract Motivation Identifying cancer driver genes is a key task in cancer informatics. Most existing methods are focused on individual cancer drivers which regulate biological processes leading to cancer. However, the effect of a single gene may not be sufficient to drive cancer progression. Here, we hypothesize that there are driver gene groups that work in concert to regulate cancer, and we develop a novel computational method to detect those driver gene groups. Results We develop a novel method named DriverGroup to detect driver gene groups by using gene expression and gene interaction data. The proposed method has three stages: (i) constructing the gene network, (ii) discovering critical nodes of the constructed network and (iii) identifying driver gene groups based on the discovered critical nodes. Before evaluating the performance of DriverGroup in detecting cancer driver groups, we firstly assess its performance in detecting the influence of gene groups, a key step of DriverGroup. The application of DriverGroup to DREAM4 data demonstrates that it is more effective than other methods in detecting the regulation of gene groups. We then apply DriverGroup to the BRCA dataset to identify driver groups for breast cancer. The identified driver groups are promising as several group members are confirmed to be related to cancer in literature. We further use the predicted driver groups in survival analysis and the results show that the survival curves of patient subpopulations classified using the predicted driver groups are significantly differentiated, indicating the usefulness of DriverGroup. Availability and implementation DriverGroup is available at https://github.com/pvvhoang/DriverGroup Supplementary information Supplementary data are available at Bioinformatics online.

Funder

ARC DECRA

Australian Research Council Discovery

Publisher

Oxford University Press (OUP)

Subject

Computational Mathematics,Computational Theory and Mathematics,Computer Science Applications,Molecular Biology,Biochemistry,Statistics and Probability

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