Constructing Disease Similarity Networks Based on Disease Module Theory

Quantifying the associations between diseases is now playing an important role in modern biology and medicine. Actually discovering associations between diseases could help us gain deeper insights into pathogenic mechanisms of complex diseases, thus could lead to improvements in disease diagnosis, drug repositioning, and drug development. Due to the growing body of high-throughput biological data, a number of methods have been developed for computing similarity between diseases during the past decade. However, these methods rarely consider the interconnections of genes related to each disease in protein-protein interaction network (PPIN). Recently, the disease module theory has been proposed, which states that disease-related genes or proteins tend to interact with each other in the same neighborhood of a PPIN. In this study, we propose a new method called ModuleSim to measure associations between diseases by using disease-gene association data and PPIN data based on disease module theory. The experimental results show that by considering the interactions between disease modules and their modularity, the disease similarity calculated by ModuleSim has a significant correlation with disease classification of Disease Ontology (DO). Furthermore, ModuleSim outperforms other four popular methods which are all using disease-gene association data and PPIN data to measure disease-disease associations. In addition, the disease similarity network constructed by MoudleSim suggests that ModuleSim is capable of finding potential associations between diseases.