the implications of relationships between human diseases and metabolic subpathways的影响人类疾病和代谢subpathways之间的关系.pdf

The Implications of Relationships between Human Diseases and Metabolic Subpathways 1 . 1. 1. 1 1 2 1 Xia Li * , Chunquan Li , Desi Shang , Jing Li , Junwei Han , Yingbo Miao , Yan Wang , Qianghu 1 1 1 1 1 1 Wang , Wei Li , Chao Wu , Yunpeng Zhang , Xiang Li , Qianlan Yao 1 Bio-Pharmaceutical Key Laboratory of Heilongjiang Province, and College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China, 2 College of Pharmacy, Nankai University, Tianjin, China Abstract One of the challenging problems in the etiology of diseases is to explore the relationships between initiation and progression of diseases and abnormalities in local regions of metabolic pathways. To gain insight into such relationships, we applied the ‘‘k-clique’’ subpathway identification method to all disease-related gene sets. For each disease, the disease risk regions of metabolic pathways were then identified and considered as subpathways associated with the disease. We finally built a disease-metabolic subpathway network (DMSPN). Through analyses based on network biology, we found that a few subpathways, such as that of cytochrome P450, were highly connected with many diseases, and most belonged to fundamental metabolisms, suggesting that abnormalities of fundamental metabolic processes tend to cause more types of diseases. According to the categories of diseases and subpathways, we tested the clustering phenomenon of diseases and metabolic subpathways in the DMSPN. The results showed that both disease nodes and subpathway nodes displayed slight clustering phenomenon. We also tested correlations