A model and algorithm for identifying driver pathways based on weighted non-binary mutation matrix

摘要

It is generally acknowledged that driver pathway plays a decisive role in the occurrence and progress of tumors, and the identification of driver pathways has become imperative for precision medicine or personalized medicine. Due to the inevitable sequencing error, the noise contained in single omics cancer data usually plays a negative effect on identification. It is a feasible approach to take advantage of multi-omics cancer data rather than a single one now that large amounts of multi-omics cancer data have become available. The identification of driver pathways by integrating multi-omics cancer data has attracted attention of researchers in bioinformatics recently. In this paper, a weighted non-binary mutation matrix is constructed by integrating copy number variations, somatic mutations and gene expressions. Based on the weighted non-binary mutation matrix, a new identification model is proposed through defining new measurements of coverage and exclusivity. Then, a cooperative coevolutionary algorithm CGA-MWS is put forward for solving the presented model. Both real cancer data and simulated one were used to conduct comparisons among methods Dendrix, GA, iMCMC, MOGA, PGA-MWS and CGA-MWS. Compared with the pathways identified by the other five methods, more genes, belonging to the pathway identified by the CGA-MWS method, are enriched in a known signaling pathway in most cases. Simultaneously, the high efficiency of method CGA-MWS makes it practical in realistic applications. All of which have been verified through a number of experiments.