Prioritization of rheumatoid arthritis risk subpathways based on global immune subpathway interaction network and random walk strategy

Abstract

The initiation and development of rheumatoid arthritis (RA) is closely related to mutual dysfunction of multiple pathways. Furthermore, some similar molecular mechanisms are shared between RA and other immune diseases. Therefore it is vital to reveal the molecular mechanism of RA through searching for subpathways of immune diseases and investigating the crosstalk effect among subpathways. Here we exploited an integrated approach combining both construction of a subpathway–subpathway interaction network and a random walk strategy to prioritize RA risk subpathways. Our research can be divided into three parts: (1) acquisition of risk genes and identification of risk subpathways of 85 immune diseases by using subpathway-lenient distance similarity (subpathway-LDS) method; (2) construction of a global immune subpathway interaction (GISI) network with subpathways identified by subpathway-LDS; (3) optimization of RA risk subpathways by random walk strategy based on GISI network. The results showed that our method could effectively identify RA risk subpathways, such as MAPK signaling pathway, prostate cancer pathway and chemokine signaling pathway. The integrated strategy considering crosstalk between immune subpathways significantly improved the effect of risk subpathway identification. With the development of GWAS, our method will provide insight into exploring molecular mechanisms of immune diseases and might be a promising approach for studying other diseases.