Quantitative Biology

, Volume 3, Issue 3, pp 124–134 | Cite as

Network-based method to infer the contributions of proteins to the etiology of drug side effects

  • Rui Li
  • Ting Chen
  • Shao Li
Research Article


Studying the molecular mechanisms that underlie the relationship between drugs and the side effects they produce is critical for drug discovery and drug development. Currently, however, computational methods are still unavailable to assess drug-protein interactions with the aim of globally inferring the contributions of various classes of proteins toward the etiology of side effects. In this work, we integrated data reflecting drug-side effect relationships, drugtarget relationships, and protein-protein interactions to develop a novel network-based probabilistic model, SidePro, to evaluate the contributions of proteins toward the etiology of side effects. For a given side effect, the method applies an expectation—maximization algorithm and a diffusion kernel-based approach to estimate each protein’s contribution. We applied this method to a wide range of side effects and validated the results using cross-validation and records from the Side Effect Resource database. We also studied a specific side effect, nephrotoxicity, which is known to be associated with the irrational use of the Chinese herbal compound triptolide, a diterpenoid epoxide in the Thunder of God Vine, Tripterygium wilfordii (Lei-Gong-Teng). Using triptolide as an example, we scored the target proteins of triptolide using our model and investigated the high-scoring proteins and their related biological processes. The results demonstrated that our model could differentiate between the potential side effect targets and therapeutic targets of triptolide. Overall, the proposed model could accurately pinpoint the molecular mechanisms of drug side effects, thus making contribution to safe and effective drug development.


network pharmacology drug targets side effects triptolide 


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Copyright information

© Higher Education Press and Springer-Verlag GmbH 2015

Authors and Affiliations

  1. 1.MOE Key Laboratory of Bioinformatics and Bioinformatics Division, TNLIST, Department of AutomationTsinghua UniversityBeijingChina
  2. 2.Program in Computational Biology and BioinformaticsUniversity of Southern CaliforniaLos AngelesUSA

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