An Integrated Framework for Identifying Mutated Driver Pathway and Cancer Progression

Abstract

Next-generation sequencing (NGS) technologies provide amount of somatic mutation data in a large number of patients. The identification of mutated driver pathway and cancer progression from these data is a challenging task because of the heterogeneity of interpatient. In addition, cancer progression at the pathway level has been proved to be more reasonable than at the gene level. In this paper, we introduce an integrated framework to identify mutated driver pathways and cancer progression (iMDPCP) at the pathway level from somatic mutation data. First, we use uncertainty coefficient to quantify mutual exclusivity on gene driver pathways and develop a computational framework to identify mutated driver pathways based on the adaptive discrete differential evolution algorithm. Then, we construct cancer progression model for driver pathways based on the Bayesian Network. Finally, we evaluate the performance of iMDPCP on real cancer somatic mutation datasets. The experimental results indicate that iMDPCP is more accurate than state-of-the-art methods according to the enrichment of KEGG pathways, and it also provides new insights on identifying cancer progression at the pathway level.