Mixture drug-count response model for the high-dimensional drug combinatory effect on myopathy.
アブストラクト Drug-drug interactions (DDIs) are a common cause of adverse drug events (ADEs). The electronic medical record (EMR) database and the FDA's adverse event reporting system (FAERS) database are the major data sources for mining and testing the ADE associated DDI signals. Most DDI data mining methods focus on pair-wise drug interactions, and methods to detect high-dimensional DDIs in medical databases are lacking. In this paper, we propose 2 novel mixture drug-count response models for detecting high-dimensional drug combinations that induce myopathy. The "count" indicates the number of drugs in a combination. One model is called fixed probability mixture drug-count response model with a maximum risk threshold (FMDRM-MRT). The other model is called count-dependent probability mixture drug-count response model with a maximum risk threshold (CMDRM-MRT), in which the mixture probability is count dependent. Compared with the previous mixture drug-count response model (MDRM) developed by our group, these 2 new models show a better likelihood in detecting high-dimensional drug combinatory effects on myopathy. CMDRM-MRT identified and validated (54; 374; 637; 442; 131) 2-way to 6-way drug interactions, respectively, which induce myopathy in both EMR and FAERS databases. We further demonstrate FAERS data capture much higher maximum myopathy risk than EMR data do. The consistency of 2 mixture models' parameters and local false discovery rate estimates are evaluated through statistical simulation studies. 投稿日 2017/11/25 投稿者 Wang, Xueying; Zhang, Pengyue; Chiang, Chien-Wei; Wu, Hengyi; Shen, Li; Ning, Xia; Zeng, Donglin; Wang, Lei; Quinney, Sara K; Feng, Weixing; Li, Lang ジャーナル名 Statistics in medicine 組織名 Institute of Intelligent System and Bioinformatics, College of Automation, Harbin;Engineering University, NO.145-1, Nantong Street, Nangang District, Harbin,;150001, Heilongjiang, China.;Center for Computational Biology and Bioinformatics, School of Medicine, Indiana;University, 410 W. 10th St., Suite 5000, Indianapolis, IN, 46202, USA.;Department of Radiology, School of Medicine, Indiana University, 355 W. 16th;Street, Suite 4100, Room 4099, Indianapolis, 46202, IN, USA.;Computer and Information Science, IUPUI, 723 W Michigan St, SL 265, Indianapolis,;IN, 46202, USA.;Department of Biostatistics, University of North Carolina at Chapel Hill, 3103B;McGavran-Greenberg Hall, CB #7420, Chapel Hill, NC, 27599, USA.;Department of Medical and Molecular Genetics, School of Medicine, Indiana;University, 975 West Walnut Street, Medical Research and Library Building, IB;130, Indianapolis, 46202, IN, USA.;Department of Obstetrics and Gynecology, School of Medicine, Indiana University,;550 University Blvd, Indianapolis, 46202, IN, USA.;Division of Clinical Pharmacology, School of Medicine, Indiana University,;Research Institute (R2), Room 402, 950 West Walnut Street, Indianapolis, 46202,;IN, USA.;Indiana Institute of Personalized Medicine, School of Medicine, Indiana;University, Research Institute (R2), Room 402, 950 West Walnut Street,;Indianapolis, 46202, IN, USA. Pubmed リンク https://www.ncbi.nlm.nih.gov/pubmed/29171062/