A network-based method for identifying cancer driver genes based on node control centrality.

Abstract

Cancer is one of the major contributors to human mortality and has a serious influence on human survival and health. In biomedical research, the identification of cancer driver genes (cancer drivers for short) is an important task; cancer drivers can promote the progression and generation of cancer. To identify cancer drivers, many methods have been developed. These computational models only identify coding cancer drivers; however, non-coding drivers likewise play significant roles in the progression of cancer. Hence, we propose a Network-based Method for identifying cancer Driver Genes based on node Control Centrality (NMDGCC), which can identify coding and non-coding cancer driver genes. The process of NMDGCC for identifying driver genes mainly includes the following two steps. In the first step, we construct a gene interaction network by using mRNAs and miRNAs expression data in the cancer state. In the second step, the control centrality of the node is used to identify cancer drivers in the constructed network. We use the breast cancer dataset from The Cancer Genome Atlas (TCGA) to verify the effectiveness of NMDGCC. Compared with the existing methods of cancer driver genes identification, NMDGCC has a better performance. NMDGCC also identifies 295 miRNAs as non-coding cancer drivers, of which 158 are related to tumorigenesis of BRCA. We also apply NMDGCC to identify driver genes related to the different breast cancer subtypes. The result shows that NMDGCC detects many cancer drivers of specific cancer subtypes.