Candidate gene prioritization for non-communicable diseases based on functional information: Case studies

Abstract

Candidate gene prioritization for complex non-communicable diseases is essential to understanding the mechanism and developing better means for diagnosing and treating these diseases. Many methods have been developed to prioritize candidate genes in protein-protein interaction (PPI) networks. Integrating functional information/similarity into disease-related PPI networks could improve the performance of prioritization. In this study, a candidate gene prioritization method was proposed for non-communicable diseases considering disease risks transferred between genes in weighted disease PPI networks with weights for nodes and edges based on functional information. Here, three types of non-communicable diseases with pathobiological similarity, Type 2 diabetes (T2D), coronary artery disease (CAD) and dilated cardiomyopathy (DCM), were used as case studies. Literature review and pathway enrichment analysis of top-ranked genes demonstrated the effectiveness of our method. Better performance was achieved after comparing our method with other existing methods. Pathobiological similarity among these three diseases was further investigated for common top-ranked genes to reveal their pathogenesis.

Keywords: Candidate gene prioritization; Functional information; Non-communicable diseases; Pathobiological similarity; Protein-protein interaction networks.