Two-stage-vote ensemble framework based on integration of mutation data and gene interaction network for uncovering driver genes.

Identifying driver genes, exactly from massive genes with mutations, promotes accurate diagnosis and treatment of cancer. In recent years, a lot of works about uncovering driver genes based on integration of mutation data and gene interaction networks is gaining more attention. However, it is in suspense if it is more effective for prioritizing driver genes when integrating various types of mutation information (frequency and functional impact) and gene networks. Hence, we build a two-stage-vote ensemble framework based on somatic mutations and mutual interactions. Specifically, we first represent and combine various kinds of mutation information, which are propagated through networks by an improved iterative framework. The first vote is conducted on iteration results by voting methods, and the second vote is performed to get ensemble results of the first poll for the final driver gene list. Compared with four excellent previous approaches, our method has better performance in identifying driver genes on $33$ types of cancer from The Cancer Genome Atlas. Meanwhile, we also conduct a comparative analysis about two kinds of mutation information, five gene interaction networks and four voting strategies. Our framework offers a new view for data integration and promotes more latent cancer genes to be admitted.

A systematic view of computational methods for identifying driver genes based on somatic mutation data.

Abnormal changes of driver genes are serious for human health and biomedical research. Identifying driver genes, exactly from enormous genes with mutations, promotes accurate diagnosis and treatment of cancer. A lot of works about uncovering driver genes have been developed over the past decades. By analyzing previous works, we find that computational methods are more efficient than traditional biological experiments when distinguishing driver genes from massive data. In this study, we summarize eight common computational algorithms only using somatic mutation data. We first group these methods into three categories according to mutation features they apply. Then, we conclude a general process of nominating candidate cancer driver genes. Finally, we evaluate three representative methods on 10 kinds of cancer derived from The Cancer Genome Atlas Program and five Chinese projects from the International Cancer Genome Consortium. In addition, we compare results of methods with various parameters. Evaluation is performed from four perspectives, including CGC, OG/TSG, Q-value and QQQuantile-Quantileplot. To sum up, we present algorithms using somatic mutation data in order to offer a systematic view of various mutation features and lay the foundation of methods based on integration of mutation information and other types of data.