Improving the Identification of Co-occurring Driver Pathways by Integrating Multi-Omics Data

Abstract

It is widely accepted that driver pathways offer important information for precision and personalized medicine of cancer treatment, hence the problems of driver pathways identification have become a research hotspot in bioinformatics. In this paper, an improved collaborative mutation driver pathways model ICMDP is proposed by integrating the somatic mutation, copy number variation and gene expression data. The model has two characteristics:(1) each individual pathway has moderate mutual exclusion and high coverage; (2) collaborative driver pathways exhibit significant common mutations in cancer samples, and the genes in collaborative driver pathways are related. Meanwhile, a parthenogenetic algorithm PA-ICMDP is proposed for solving the ICMDP model. Experiments were performed to compare algorithms PA-ICMDP, CoMDP and GAMTOC by using real biological data sets, i.e., the samples of glioblastoma and ovarian. The experimental results indicate that the PA-ICMDP algorithm can not only identify important collaborative driver pathways with higher co-occurrence mutation rates, but also detect more important driver genes such as MET, MDM2, GAB2, TERT, TBX3 and so on. In addition, the EICMDP model and the PA-EICMDP algorithm are put forward by extending the ICMDP model and the PAICMDP algorithm respectively. They can effectively identify other important pathways that collaborate with known driver pathways. The experimental results indicate that the methods presented in this paper may become suitable tools for mining driver genes and driver pathways related to cancer development.