Analysis of disease organ as a novel phenotype towards disease genetics understanding

Discerning the modular nature of human diseases through computational approaches calls for diverse data. The finding sites of diseases, like other disease phenotypes, possess rich information in understanding disease genetics. Yet, analysis of the rich knowledge of disease finding sites has not been comprehensively investigated. In this study, we built a large-scale disease organ network (DON) based on 76,561 disease-organ associations (for 37,615 diseases and 3492 organs) extracted from the United Medical Language System (UMLS) Metathesaurus. We investigated how phenotypic organ similarity among diseases in DON reflects disease gene sharing. We constructed a disease genetic network (DGN) using curated disease-gene associations and demonstrated that disease pairs with higher organ similarities not only are more likely to share genes, but also tend to share more genes. Based on community detection algorithm, we showed that phenotypic disease clusters on DON significantly correlated with genetic disease clusters on DGN. We compared DON with a state-of-art disease phenotype network, disease manifestation network (DMN), that we have recently constructed, and demonstrated that DON contains complementary knowledge for disease genetics understanding.