BackgroundCancer is a complex disease which is characterized by the accumulation of genetic alterations during the patient’s lifetime. With the development of the next-generation sequencing technology, multiple omics data, such as cancer genomic, epigenomic and transcriptomic data etc., can be measured from each individual. Correspondingly, one of the key challenges is to pinpoint functional driver mutations or pathways, which contributes to tumorigenesis, from millions of functional neutral passenger mutations.ResultsIn this paper, in order to identify driver genes effectively, we applied a generalized additive model to mutation profiles to filter genes with long length and constructed a new gene-gene interaction network. Then we integrated the mutation data and expression data into the gene-gene interaction network. Lastly, greedy algorithm was used to prioritize candidate driver genes from the integrated data. We named the proposed method Length-Net-Driver (LNDriver).ConclusionsExperiments on three TCGA datasets, i.e., head and neck squamous cell carcinoma, kidney renal clear cell carcinoma and thyroid carcinoma, demonstrated that the proposed method was effective. Also, it can identify not only frequently mutated drivers, but also rare candidate driver genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-016-1332-y) contains supplementary material, which is available to authorized users.
Identifying driver genes that contribute to cancer progression from numerous passenger genes, although a central goal, is a major challenge. The protein-protein interaction network provides convenient and reasonable assistance for driver gene discovery. Random walk-based methods have been widely used to prioritize nodes in social or biological networks. However, most studies select the next arriving node uniformly from the random walker's neighbors. Few consider transiting preference according to the degree of random walker's neighbors. In this study, based on the random walk method, we propose a novel approach named Driver_IRW (Driver genes discovery with Improved Random Walk method), to prioritize cancer genes in cancer-related network. The key idea of Driver_IRW is to assign different transition probabilities for different edges of a constructed cancer-related network in accordance with the degree of the nodes' neighbors. Furthermore, the global centrality (here is betweenness centrality) and Katz feedback centrality are incorporated into the framework to evaluate the probability to walk to the seed nodes. Experimental results on four cancer types indicate that Driver_IRW performs more efficiently than some previously published methods for uncovering known cancer-related genes. In conclusion, our method can aid in prioritizing cancer-related genes and complement traditional frequency and network-based methods.
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