A nonlinear model and an algorithm for identifying cancer driver pathways

Abstract

The identification of driver pathways has attracted considerable attention in recent years due to the high significance of driver pathways in cancer related studies. In most identification methods, the linear measurement is adopted for evaluating exclusivity, and some preset parameters are introduced to balance the contributions of different measurements. However, both the linear measurement and the preset parameters may exert negative effects on the applications of these methods. In this study, a nonlinear function is devised to measure exclusivity, and a parameter free nonlinear maximum weight submatrix (NMWS) identification model is proposed by considering coverage, exclusivity and connectivity. A competitive co-evolution algorithm (CCA) is also put forward for solving the presented NMWS model. Experimental results on both real biological data and simulated one were used compare the identification performance of the presented method with that of seven state of the art ones. The pathway detected by the presented method not only contains more genes enriched in a known signaling pathway, but also has a stronger connectivity in Protein–Protein Interaction (PPI) network. Simultaneously, the high efficiency of the presented method makes it practical in realistic applications. All of which have been confirmed through a large number of experiments.