Identifying Cancer Driver Pathways Based on the Mouth Brooding Fish Algorithm

Abstract

Identifying the driver genes of cancer progression is of great significance in improving our understanding of the causes of cancer and promoting the development of personalized treatment. In this paper, we identify the driver genes at the pathway level via an existing intelligent optimization algorithm, named the Mouth Brooding Fish (MBF) algorithm. Many methods based on the maximum weight submatrix model to identify driver pathways attach equal importance to coverage and exclusivity and assign them equal weight, but those methods ignore the impact of mutational heterogeneity. Here, we use principal component analysis (PCA) to incorporate covariate data to reduce the complexity of the algorithm and construct a maximum weight submatrix model considering different weights of coverage and exclusivity. Using this strategy, the unfavorable effect of mutational heterogeneity is overcome to some extent. Data involving lung adenocarcinoma and glioblastoma multiforme were tested with this method and the results compared with the MDPFinder, Dendrix, and Mutex methods. When the driver pathway size was 10, the recognition accuracy of the MBF method reached 80% in both datasets, and the weight values of the submatrix were 1.7 and 1.89, respectively, which are better than those of the compared methods. At the same time, in the signal pathway enrichment analysis, the important role of the driver genes identified by our MBF method in the cancer signaling pathway is revealed, and the validity of these driver genes is demonstrated from the perspective of their biological effects.

Keywords

• cancer progression
• driver gene coverage
• driver pathway
• biological effects