단백질 상호작용 네트워크에서 multipath가 공존질환에 미치는 영향

Abstract

Human diseases are often associated with each other in a similar phenotype or co-occur in the same individual as a comorbid disease. Molecular connections of human diseases have been under intense investigation and found to be explained by either shared genes or protein-protein interactions (PPIs) which connect disease genes into phenotypically similar disease modules. These network connections of disease genes are crucial to establish genotype-phenotype relationship of human diseases. However, human interactome map remains incomplete thus that disease pairs that can be explained by direct PPIs are limited. Here, we investigated multipath interactions of disease genes occurred in human PPI network and discovered that indirect but multipath PPIs explain the phenotypic relationship of comorbid disease pairs. Multipath of disease genes successfully increase the coverage of disease pairs explained by current PPI network. Furthermore, we found that disease pairs connected by multipath interactions tend to share biological functions and subcellular localizations. Multipath interactions in the PPI network expand the molecular connections of phenotypic relationships among disease modules, important for the understanding of disease progression and diagnosis.