Abstract

BackgroundUnderstanding the genetic networks and their role in chronic diseases (e.g., cancer) is one of the important objectives of biological researchers. In this work, we present a text mining system that constructs a gene-gene-interaction network for the entire human genome and then performs network analysis to identify disease-related genes. We recognize the interacting genes based on their co-occurrence frequency within the biomedical literature and by employing linear and non-linear rare-event classification models. We analyze the constructed network of genes by using different network centrality measures to decide on the importance of each gene. Specifically, we apply betweenness, closeness, eigenvector, and degree centrality metrics to rank the central genes of the network and to identify possible cancer-related genes.ResultsWe evaluated the top 15 ranked genes for different cancer types (i.e., Prostate, Breast, and Lung Cancer). The average precisions for identifying breast, prostate, and lung cancer genes vary between 80-100%. On a prostate case study, the system predicted an average of 80% prostate-related genes.ConclusionsThe results show that our system has the potential for improving the prediction accuracy of identifying gene-gene interaction and disease-gene associations. We also conduct a prostate cancer case study by using the threshold property in logistic regression, and we compare our approach with some of the state-of-the-art methods.

Highlights

  • Understanding the genetic networks and their role in chronic diseases is one of the important objectives of biological researchers

  • In “Disease-gene association” section, we describe the process of extracting disease-gene associations based on network analysis

  • We first retrieve an initial list of genes associated with the target cancer type, using Online Mendelian Inheritance in Man (OMIM) database

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Summary

Introduction

Understanding the genetic networks and their role in chronic diseases (e.g., cancer) is one of the important objectives of biological researchers. According to NCCDPHP (National Center for Chronic Disease Prevention and Health Promotion), cancer is among the top 10 causes of deaths for 2014 in the United States [1]. Mutations in genes lead to harmful consequences and genetic diseases [4]. Genetic mutations would lead to the creation of nonfunctional proteins. For genes coding for proteins involved in cell division, a mutation will interrupt the normal process of cell proliferation and death [5]. Any alteration or mutation to these genes will disrupt the normal cell division process resulting in cell division over-activation, and will eventually lead to the development of a tumor (cancer)

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