Abstract

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.

Highlights

  • As one of the most complex and threatening diseases, cancer has attracted the attention of many research groups and large-scale programs [such as The Cancer Genome Atlas (TCGA) (Network, 2008) and the International Cancer Genome Consortium (Bobrow and Zhao, 2010)] to explore the molecular mechanisms and pathogenesis

  • Chen et al (2016) have proposed an improved random walk with restart method for lncRNA-disease association prediction (IRWRLDA). These two methods improve the initial probabilities of restart term by Abbreviations: TCGA, The Cancer Genome Atlas; ICGC, International Cancer Genome Consortium; single-nucleotide variants (SNVs), Single Nucleotide Variants; copy number variations (CNVs), Copy Number Variations; insertions and deletions (Indels), Insertions and Deletions; BMR, Background Mutation Rates; breast cancer (BRCA), Breast Cancer; head and neck squamous cell carcinoma (HNSC), Head and Neck Squamous Cell Carcinoma; kidney renal cell cancer (KIRC), Clear Cell Kidney Carcinoma; thyroid cancer (THCA), Thyroid Carcinoma; PCC, Pearson Correlation Coefficients; DC, Degree Centrality; BC, Betweenness Centrality; KC, Katz Centrality

  • It was regarded as a mutated gene if there was an SNV or CNV present, in which the CNV data are downloaded from UCSC data portal (Rosenbloom et al, 2015), which have transformed the data from TCGA using Gistic2 method

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Summary

Introduction

As one of the most complex and threatening diseases, cancer has attracted the attention of many research groups and large-scale programs [such as The Cancer Genome Atlas (TCGA) (Network, 2008) and the International Cancer Genome Consortium (Bobrow and Zhao, 2010)] to explore the molecular mechanisms and pathogenesis. Chen et al (2016) have proposed an improved random walk with restart method for lncRNA-disease association prediction (IRWRLDA) These two methods improve the initial probabilities of restart term by Abbreviations: TCGA, The Cancer Genome Atlas; ICGC, International Cancer Genome Consortium; SNVs, Single Nucleotide Variants; CNVs, Copy Number Variations; Indels, Insertions and Deletions; BMR, Background Mutation Rates; BRCA, Breast Cancer; HNSC, Head and Neck Squamous Cell Carcinoma; KIRC, Clear Cell Kidney Carcinoma; THCA, Thyroid Carcinoma; PCC, Pearson Correlation Coefficients; DC, Degree Centrality; BC, Betweenness Centrality; KC, Katz Centrality

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