Human Pathway-Based Disease Network.

Constructing disease-disease similarity network is important in elucidating the associations between the origin and molecular mechanism of diseases, and in researching disease function and medical research. In this paper, we use a high-quality protein interaction network and a collection of pathway databases to construct a Human Pathway-based Disease Network (HPDN) to explore the relationship between diseases and their intrinsic interactions. We find that the similarity of two diseases has a strong correlation with the number of their shared functional pathways and the interaction between their related gene sets. Comparing HPDN with disease networks based on genes and symptoms respectively, we find the three networks have high overlap rates. Additionally, HPDN can predict new disease-disease correlations, which are supported by Comparative Toxicogenomics Database (CTD) benchmark and large-scale biomedical literature database. The comprehensive, high-quality relations between diseases based on pathways can further be applied to study important matters in systems medicine, for instance, drug repurposing. Based on a dense subgraph in our network, we find two drugs, prednisone and folic acid, may have new indications, which will provide potential directions for the treatments of complex diseases.