Exploring disease comorbidity in a module-module interaction network

Understanding disease comorbidity contributes to improved quality of life in patients who are suffering from multiple diseases. Therefore, to better explore comorbid diseases, the clarification of associations between diseases based on biological functions is essential. In our study, we propose a method for identifying disease comorbidity in a module-based network, named the module-module interaction (MMI) network, which represents how biological functions influence each other. To construct the MMI network, we detected gene modules - sets of genes that have a higher probability of taking part in specific functions - and established a link between these modules. Subsequently, we constructed disease-related networks in the MMI network to understand inherent disease mechanisms and calculated comorbidity scores of disease pairs using Gene Ontology (GO) terms. Our results show that we can obtain further information on disease mechanisms by considering interactions between functional modules instead of between genes. In addition, we verified that predicted comorbid relationships of disease pairs based on the MMI network are more significant than those based on the protein-protein interaction (PPI) network. This study can be useful to elucidate the mechanisms underlying comorbidities for further study, which will provide a broader insight into the pathogenesis of diseases.