title: Predicting unintended effects of drugs based on off-target tissue effects.
abstract: Unintended effects of drugs can be caused by various mechanisms. Conventional analysis of unintended effects has focused on the target proteins of drugs. However, an interaction with off-target tissues of a drug might be one of the unintended effect-related mechanisms. We propose two processes to predict a drug's unintended effects by off-target tissue effects: 1) identification of a drug's off-target tissue and; 2) tissue protein - symptom relation identification (tissue protein - symptom matrix). Using this method, we predicted that 1,177 (10.7%) side-effects were related to off-target tissue effects in 11,041 known side-effects. Off-target tissues and unintended effects of successful repositioning drugs were also predicted. The effectiveness of relations of the proposed tissue protein - symptom matrix were evaluated by using the literature mining method. We predicted unintended effects of drugs as well as those effect-related off-target tissues. By using our prediction, we are able to reduce drug side-effects on off-target tissues and provide a chance to identify new indications of drugs of interest.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Docyong
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Jaehyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Sunjae
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
authors.forename: Junseok
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea; Bio-Synergy Research Center, Daejeon, Republic of Korea. Electronic address: dhlee@kaist.ac.kr.
authors.forename: Doheon
authors.initials: D
authors.lastname: Lee
mesh_terms: D015195:Drug Design; D058492:Drug Repositioning / Q000379:methods*; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D006801:Humans; D009928:Organ Specificity / Q000502:physiology; D055553:Prescription Drugs / Q000009:adverse effects* / Q000378:metabolism*; D025941:Protein Interaction Mapping / Q000379:methods*; D020543:Proteome / Q000378:metabolism*
chemical_list: D055553:Prescription Drugs; D020543:Proteome
keywords: Drug repositioning; Off-target tissue effect; Side-effect prediction; Tissue protein-symptom matrix; Unintended effect