title: Network characteristic analysis of ADR-related proteins and identification of ADR-ADR associations.
abstract: Adverse drug reactions (ADRs) are caused by interactions between drugs or their metabolites and specific proteins. Knowledge of these proteins is important for facilitating mechanistic research of ADRs and new drug discovery. Here, we identified 41 network modules from an ADR-protein network; analysed the function of each module; revealed the potential accompanying actions of the ADRs and the new ADR-related proteins (ADRPs) to a unique ADR and studied the characteristics of composition, subcellular location and tissue distribution of these ADRPs by comparing them with drug-related proteins (DRPs). The results indicated that ADRs are mainly caused by risk drug-related proteins (RDRPs) and that drug off-target effects are a secondary cause. Biological processes that enzymes involve are the main reason for the occurrence of ADRs. However, drug-related transporters have a higher risk of inducing ADRs than drug-related enzymes do, and ADRPs locating in the cell membrane tend to induce multiple ADRs.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, PR China. chenxiujie@ems.hrbmu.edu.cn
authors.forename: Xiujie
authors.initials: X
authors.lastname: Chen
authors.forename: Xiangqiong
authors.initials: X
authors.lastname: Liu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Jia
authors.forename: Fujian
authors.initials: F
authors.lastname: Tan
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Yang
authors.forename: Sheng
authors.initials: S
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism*; D006801:Humans; D010600:Pharmacology; D011506:Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D011506:Proteins