Enhancing Cancer Driver Gene Prediction by Protein-Protein Interaction Network.

Abstract

With the advances in gene sequencing technologies, millions of somatic mutations have been reported in the past decades, but mining cancer driver genes with oncogenic mutations from these data remains a critical and challenging area of research. In this study, we proposed a network-based classification method for identifying cancer driver genes with merging the multi-biological information. In this method, we construct a cancer specific genetic network from the human protein-protein interactome (PPI) to mine the network structure attributes, and combine biological information such as mutation frequency and differential expression of genes to achieve accurate prediction of cancer driver genes. Across seven different cancer types, the proposed algorithm always achieves high prediction accuracy, which is superior to the existing advanced methods. In the analysis of the predicted results, about 40 percent of the top 10 candidate genes overlap with the Cancer Gene Census database. Interestingly, the feature comparison indicates that the network based features are still more important than the biological features, including the mutation frequency and genetic differential expression. Further analyses also show that the integration of network structure attributes and biological information is valuable for predicting new cancer driver genes.