title: Large-scale exploration and analysis of drug combinations.
abstract: BACKGROUND
  Drug combinations are a promising strategy for combating complex diseases by improving the efficacy and reducing corresponding side effects. Currently, a widely studied problem in pharmacology is to predict effective drug combinations, either through empirically screening in clinic or pure experimental trials. However, the large-scale prediction of drug combination by a systems method is rarely considered.
  
  
  RESULTS
  We report a systems pharmacology framework to predict drug combinations (PreDCs) on a computational model, termed probability ensemble approach (PEA), for analysis of both the efficacy and adverse effects of drug combinations. First, a Bayesian network integrating with a similarity algorithm is developed to model the combinations from drug molecular and pharmacological phenotypes, and the predictions are then assessed with both clinical efficacy and adverse effects. It is illustrated that PEA can predict the combination efficacy of drugs spanning different therapeutic classes with high specificity and sensitivity (AUC = 0.90), which was further validated by independent data or new experimental assays. PEA also evaluates the adverse effects (AUC = 0.95) quantitatively and detects the therapeutic indications for drug combinations. Finally, the PreDC database includes 1571 known and 3269 predicted optimal combinations as well as their potential side effects and therapeutic indications.
  
  
  METHODS
  The PreDC database is available at http://sm.nwsuaf.edu.cn/lsp/predc.php.
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Peng
authors: P
authors: Li
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Chao
authors: C
authors: Huang
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Yingxue
authors: Y
authors: Fu
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Jinan
authors: J
authors: Wang
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Ziyin
authors: Z
authors: Wu
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Jinlong
authors: J
authors: Ru
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Chunli
authors: C
authors: Zheng
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Zihu
authors: Z
authors: Guo
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Xuetong
authors: X
authors: Chen
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Wei
authors: W
authors: Zhou
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Wenjuan
authors: W
authors: Zhang
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Yan
authors: Y
authors: Li
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Jianxin
authors: J
authors: Chen
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Aiping
authors: A
authors: Lu
authors: Lab of Systems Pharmacology, Center of Bioinformatics, College of Life Science, Northwest A&F University, Yangling, Shaanxi, China, School of Chemical engineering, Dalian University of Technology, Dalian, Liaoning, China, Beijing University of Chinese Medicine, ChaoYang District, Beijing, China and School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
authors: Yonghua
authors: Y
authors: Wang
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods*; D062313:Databases, Pharmaceutical; D004338:Drug Combinations; D004347:Drug Interactions; D004357:Drug Synergism; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008962:Models, Theoretical; D011336:Probability
chemical_list: D004338:Drug Combinations