DPDR-CPI, a server that predicts Drug Positioning and Drug Repositioning via Chemical-Protein Interactome.
The cost of developing a new drug has increased sharply over the past years. To ensure a reasonable return-on-investment, it is useful for drug discovery researchers in both industry and academia to identify all the possible indications for early pipeline molecules. For the first time, we propose the term computational "drug candidate positioning" or "drug positioning", to describe the above process. It is distinct from drug repositioning, which identifies new uses for existing drugs and maximizes their value. Since many therapeutic effects are mediated by unexpected drug-protein interactions, it is reasonable to analyze the chemical-protein interactome (CPI) profiles to predict indications. Here we introduce the server DPDR-CPI, which can make real-time predictions based only on the structure of the small molecule. When a user submits a molecule, the server will dock it across 611 human proteins, generating a CPI profile of features that can be used for predictions. It can suggest the likelihood of relevance of the input molecule towards ~1,000 human diseases with top predictions listed. DPDR-CPI achieved an overall AUROC of 0.78 during 10-fold cross-validations and AUROC of 0.76 for the independent validation. The server is freely accessible via http://cpi.bio-x.cn/dpdr/.
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Heng
H
Luo
Center for Computational Health, IBM T.J. Watson Research Center, Yorktown Heights, NY 10598, USA.
Ping
P
Zhang
Center for Data Analytics and Biomedical Informatics, Temple University, Philadelphia, PA 19122, USA.
Xi Hang
XH
Cao
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Dizheng
D
Du
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Hao
H
Ye
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Hui
H
Huang
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Can
C
Li
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Shengying
S
Qin
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Chunling
C
Wan
Collaborative Innovation Center for Genetics and Development, State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200438, China.
Leming
L
Shi
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Lin
L
He
Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200030, China.
Lun
L
Yang
D019540:Area Under Curve; D058492:Drug Repositioning; D006801:Humans; D020407:Internet; D062105:Molecular Docking Simulation; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011724:Pyridazines / Q000737:chemistry / Q000378:metabolism; D012372:ROC Curve; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
C516117:4-bromo-6-(3-(4-chlorophenyl)propoxy)-5-(3-pyridylmethylamino)-3(2H)-pyridazinone hydrochloride; D004364:Pharmaceutical Preparations; D011506:Proteins; D011724:Pyridazines; D045162:Thiazolidinediones; D000077154:Rosiglitazone