Network-based characterization of disease-disease relationships in terms of drugs and therapeutic targets

Abstract

Motivation: Disease states are distinguished from each other in terms of differing clinical phenotypes, but characteristic molecular features are often common to various diseases. Similarities between diseases can be explained by characteristic gene expression patterns. However, most disease-disease relationships remain uncharacterized. Results: In this study, we proposed a novel approach for network-based characterization of disease-disease relationships in terms of drugs and therapeutic targets. We performed large-scale analyses of omics data and molecular interaction networks for 79 diseases, including adrenoleukodystrophy, leukaemia, Alzheimer's disease, asthma, atopic dermatitis, breast cancer, cystic fibrosis and inflammatory bowel disease. We quantified disease-disease similarities based on proximities of abnormally expressed genes in various molecular networks, and showed that similarities between diseases could be explained by characteristic molecular network topologies. Furthermore, we developed a kernel matrix regression algorithm to predict the commonalities of drugs and therapeutic targets among diseases. Our comprehensive prediction strategy indicated many new associations among phenotypically diverse diseases.