Studies On Type2Diabetes Mellitus By Protein-protein Interaction And Network Biology Methods

Diabetes mellitus is a complex multifactorial disease classified by abnormal metabolism and chronic hyperglycemia. Resistance to insulin action and defects in insulin secretion can result in the progress of diabetes mellitus, and type2diabetes mellitus (T2DM) accounts for over90%in the western world. Two different research methods were used in this thesis to study the generation mechanism of T2DM systematically.In chapter one, the research background and the websites and tools used were introduced briefly.In the second chapter, we screened some new potential targets of T2DM by protein-protein interactions methods. First, we constructed a largest total human protein-protein interaction set through integrating data of different websites so far. Then, we got some targets of T2DM with relating papers from the Comparative Toxicogenomics Database (CTD) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). To enlarge the extent, we obtained an expanding protein set of targets and proteins related to targets in the protein-protein interaction set. The expanding proteins were then integrated with the data of microarray gene expression values. Finally,9potential targets relating to4tissues based on the network topological theory were picked up.In the third chapter, a comprehensive pathway of T2DM was constructed. An XML format pathway based on CellDesigner was constructed by literature mining and integrating pathways. The mechanism of glucose transportation and the insulin modulation between different tissues or organs strengthened the relations of different molecules and pathways.In the last chapter, we summarized the whole thesis.