DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical-protein interactome

被引:161
作者
Luo, Heng [1 ]
Chen, Jian [1 ]
Shi, Leming [2 ]
Mikailov, Mike [3 ]
Zhu, Huang [1 ]
Wang, Kejian [1 ]
He, Lin [1 ,4 ,5 ]
Yang, Lun [1 ,2 ,4 ]
机构
[1] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China
[2] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA
[3] US FDA, Ctr Devices & Radiol Hlth, Jefferson, AR 72079 USA
[4] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China
[5] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
GENE-EXPRESSION; BREAST-CANCER; MINOCYCLINE; DISEASE; ROSIGLITAZONE; PREDICTION; SIGNATURES; LIGAND;
D O I
10.1093/nar/gkr299
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical-protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical-protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user's molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug-drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/.
引用
收藏
页码:W492 / W498
页数:7
相关论文
共 51 条
[1]   Using histamine (H1) antagonists, in particular atypical anti psychotics, to treat anemia of chronic disease via interieukin-6 suppression [J].
Altschuler, EL ;
Kast, RE .
MEDICAL HYPOTHESES, 2005, 65 (01) :65-67
[2]   Drug repositioning: Identifying and developing new uses for existing drugs [J].
Ashburn, TT ;
Thor, KB .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (08) :673-683
[3]   Quality check of spontaneous adverse drug reaction reporting forms of different countries [J].
Bandekar, M. S. ;
Anwikar, S. R. ;
Kshirsagar, N. A. .
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, 2010, 19 (11) :1181-1185
[4]   Antibacterial property of the antipsychotic agent prochlorperazine, and its synergism with methdilazine [J].
Basu, LR ;
Mazumdar, K ;
Dutta, NK ;
Karak, P ;
Dastidar, SG .
MICROBIOLOGICAL RESEARCH, 2005, 160 (01) :95-100
[5]  
Berger S, 2011, SYST BIOL MED, V3, P129
[6]   Synergistic interaction between phenothiazines and antimicrobial agents against Burkholderia pseudomallei [J].
Chan, Ying Ying ;
Ong, Yong Mei ;
Chua, Mm Lee .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2007, 51 (02) :623-630
[7]   Evaluation of phenoxybenzamine in the CFA model of pain following gene expression studies and connectivity mapping [J].
Chang, Meiping ;
Smith, Sarah ;
Thorpe, Andrew ;
Barratt, Michael J. ;
Karim, Farzana .
MOLECULAR PAIN, 2010, 6
[8]   Systematic Evaluation of Drug-Disease Relationships to Identify Leads for Novel Drug Uses [J].
Chiang, A. P. ;
Butte, A. J. .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2009, 86 (05) :507-510
[9]   Integration of biological networks and gene expression data using Cytoscape [J].
Cline, Melissa S. ;
Smoot, Michael ;
Cerami, Ethan ;
Kuchinsky, Allan ;
Landys, Nerius ;
Workman, Chris ;
Christmas, Rowan ;
Avila-Campilo, Iliana ;
Creech, Michael ;
Gross, Benjamin ;
Hanspers, Kristina ;
Isserlin, Ruth ;
Kelley, Ryan ;
Killcoyne, Sarah ;
Lotia, Samad ;
Maere, Steven ;
Morris, John ;
Ono, Keiichiro ;
Pavlovic, Vuk ;
Pico, Alexander R. ;
Vailaya, Aditya ;
Wang, Peng-Liang ;
Adler, Annette ;
Conklin, Bruce R. ;
Hood, Leroy ;
Kuiper, Martin ;
Sander, Chris ;
Schmulevich, Ilya ;
Schwikowski, Benno ;
Warner, Guy J. ;
Ideker, Trey ;
Bader, Gary D. .
NATURE PROTOCOLS, 2007, 2 (10) :2366-2382
[10]   DOSE EQUIVALENCE OF ANTI-PSYCHOTIC DRUGS [J].
DAVIS, JM .
JOURNAL OF PSYCHIATRIC RESEARCH, 1974, 11 :65-69