Disease Gene Interaction Pathways: A Potential Framework for How Disease Genes Associate by Disease-Risk Modules

BACKGROUND: Disease genes that interact cooperatively play crucial roles in the process of complex diseases, yet how to analyze and represent their associations is still an open problem. Traditional methods have failed to represent direct biological evidences that disease genes associate with each other in the pathogenesis of complex diseases. Molecular networks, assumed as ‘a form of biological systems’, consist of a set of interacting biological modules (functional modules or pathways) and this notion could provide a promising insight into deciphering this topic. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we hypothesized that disease genes might associate by virtue of the associations between biological modules in molecular networks. Then we introduced a novel disease gene interaction pathway representation and analysis paradigm, and managed to identify the disease gene interaction pathway for 61 known disease genes of coronary artery disease (CAD), which contained 46 disease-risk modules and 182 interaction relationships. As demonstrated, disease genes associate through prescribed communication protocols of common biological functions and pathways. CONCLUSIONS/SIGNIFICANCE: Our analysis was proved to be coincident with our primary hypothesis that disease genes of complex diseases interact with their neighbors in a cooperative manner, associate with each other through shared biological functions and pathways of disease-risk modules, and finally cause dysfunctions of a series of biological processes in molecular networks. We hope our paradigm could be a promising method to identify disease gene interaction pathways for other types of complex diseases, affording additional clues in the pathogenesis of complex diseases.