An Effective Method to Identify Cooperation Driver Gene Sets

Abstract

Background: In cancer genomics research, identifying driver genes is a challenging task. Detecting cancer-driver genes can further our understanding of cancer risk factors and promote the development of personalized treatments. Gene mutations show mutual exclusivity and cooccur, and most of the existing methods focus on identifying driver pathways or driver gene sets through the study of mutual exclusivity, that is functionally redundant gene sets. Moreover, less research on cooperation genes with co-occurring mutations has been conducted. Objective: We propose an effective method that combines the two characteristics of genes, cooccurring mutations and the coordinated regulation of proliferation genes, to explore cooperation driver genes. Methods: This study is divided into three stages: (1) constructing a binary gene mutation matrix; (2) combining mutation co-occurrence characteristics to identify the candidate cooperation gene sets; and (3) constructing a gene regulation network to screen the cooperation gene sets that perform synergistically regulating proliferation. Results: The method performance is evaluated on three TCGA cancer datasets, and the experiments showed that it can detect effective cooperation driver gene sets. In further investigations, it was determined that the discovered set of co-driver genes could be used to generate prognostic classifications, which could be biologically significant and provide complementary information to the cancer genome. Conclusion: Our approach is effective in identifying sets of cancer cooperation driver genes, and the results can be used as clinical markers to stratify patients.