Large-scale identification of adverse drug reaction-related proteins through a random walk model.
Adverse drug reactions (ADRs) are responsible for drug failure in clinical trials and affect life quality of patients. The identification of ADRs during the early phases of drug development is an important task. Therefore, predicting potential protein targets eliciting ADRs is essential for understanding the pathogenesis of ADRs. In this study, we proposed a computational algorithm,Integrated Network for Protein-ADR relations (INPADR), to infer potential protein-ADR relations based on an integrated network. First, the integrated network was constructed by connecting the protein-protein interaction network and the ADR similarity network using known protein-ADR relations. Then, candidate protein-ADR relations were further prioritized by performing a random walk with restart on this integrated network. Leave-one-out cross validation was used to evaluate the ability of the INPADR. An AUC of 0.8486 was obtained, which was a significant improvement compared to previous methods. We also applied the INPADR to two ADRs to evaluate its accuracy. The results suggested that the INPADR is capable of finding novel protein-ADR relations. This study provides new insight to our understanding of ADRs. The predicted ADR-related proteins will provide a reference for preclinical safety pharmacology studies and facilitate the identification of ADRs during the early phases of drug development.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Xiaowen
X
Chen
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Hongbo
H
Shi
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Feng
F
Yang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Lei
L
Yang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Yingli
Y
Lv
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Shuyuan
S
Wang
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Enyu
E
Dai
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, 150081, China.
Dianjun
D
Sun
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
Wei
W
Jiang
D000465:Algorithms; D019540:Area Under Curve; D019295:Computational Biology / Q000379:methods*; D062313:Databases, Pharmaceutical; D030562:Databases, Protein; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism*; D053263:Gene Regulatory Networks; D006801:Humans; D025941:Protein Interaction Mapping / Q000379:methods*; D060066:Protein Interaction Maps; D011506:Proteins / Q000378:metabolism*
D011506:Proteins