Complex Disease Interventions from a Network Model for Type 2 Diabetes

There is accumulating evidence that the proteins encoded by the genes associated with a common disorder interact with each other, participate in similar pathways and share GO terms. It has been anticipated that the functional modules in a disease related functional linkage network are informative to reveal significant metabolic processes and disease's associations with other complex disorders. In the current study, Type 2 diabetes associated functional linkage network (T2DFN) containing 2770 proteins and 15041 linkages was constructed. The functional modules in this network were scored and evaluated in terms of shared pathways, co-localization, co-expression and associations with similar diseases. The assembly of top scoring overlapping members in the functional modules revealed that, along with the well known biological pathways, circadian rhythm, diverse actions of nuclear receptors in steroid and retinoic acid metabolisms have significant occurrence in the pathophysiology of the disease. The disease's association with other metabolic and neuromuscular disorders was established through shared proteins. Nuclear receptor NRIP1 has a pivotal role in lipid and carbohydrate metabolism, indicating the need to investigate subsequent effects of NRIP1 on Type 2 diabetes. Our study also revealed that CREB binding protein (CREBBP) and cardiotrophin-1 (CTF1) have suggestive roles in linking Type 2 diabetes and neuromuscular diseases.