Similarity-based prediction for Anatomical Therapeutic Chemical classification of drugs by integrating multiple data sources

Zhongyang Liu; Feifei Guo; Jiangyong Gu; Yong Wang; Yang Li; Dan Wang; Liang Lu; Dong Li; Fuchu He

doi:10.1093/bioinformatics/btv055

Similarity-based prediction for Anatomical Therapeutic Chemical classification of drugs by integrating multiple data sources

Bioinformatics. 2015 Jun 1;31(11):1788-95. doi: 10.1093/bioinformatics/btv055. Epub 2015 Jan 31.

Authors

Zhongyang Liu¹, Feifei Guo², Jiangyong Gu³, Yong Wang³, Yang Li¹, Dan Wang¹, Liang Lu¹, Dong Li¹, Fuchu He¹

Affiliations

¹ State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China, National Center for Protein Sciences Beijing, Beijing 102206, China, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China, Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China and Preclinical School, Beijing University of Chinese Medicine, Beijing 100029, China State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China, National Center for Protein Sciences Beijing, Beijing 102206, China, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China, Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China and Preclinical School, Beijing University of Chinese Medicine, Beijing 100029, China.
² State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China, National Center for Protein Sciences Beijing, Beijing 102206, China, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China, Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China and Preclinical School, Beijing University of Chinese Medicine, Beijing 100029, China State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China, National Center for Protein Sciences Beijing, Beijing 102206, China, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China, Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China and Preclinical School, Beijing University of Chinese Medicine, Beijing 100029, China State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China, National Center for Protein Sciences Beijing, Beijing 102206, China, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China, Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China and Preclinical School, Beijing University of Chinese Medicine, Beijing 100029, China.
³ State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China, National Center for Protein Sciences Beijing, Beijing 102206, China, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, China, Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China and Preclinical School, Beijing University of Chinese Medicine, Beijing 100029, China.

PMID: 25638810
DOI: 10.1093/bioinformatics/btv055

Abstract

Motivation: Anatomical Therapeutic Chemical (ATC) classification system, widely applied in almost all drug utilization studies, is currently the most widely recognized classification system for drugs. Currently, new drug entries are added into the system only on users' requests, which leads to seriously incomplete drug coverage of the system, and bioinformatics prediction is helpful during this process.

Results: Here we propose a novel prediction model of drug-ATC code associations, using logistic regression to integrate multiple heterogeneous data sources including chemical structures, target proteins, gene expression, side-effects and chemical-chemical associations. The model obtains good performance for the prediction not only on ATC codes of unclassified drugs but also on new ATC codes of classified drugs assessed by cross-validation and independent test sets, and its efficacy exceeds previous methods. Further to facilitate the use, the model is developed into a user-friendly web service SPACE ( S: imilarity-based P: redictor of A: TC C: od E: ), which for each submitted compound, will give candidate ATC codes (ranked according to the decreasing probability_score predicted by the model) together with corresponding supporting evidence. This work not only contributes to knowing drugs' therapeutic, pharmacological and chemical properties, but also provides clues for drug repositioning and side-effect discovery. In addition, the construction of the prediction model also provides a general framework for similarity-based data integration which is suitable for other drug-related studies such as target, side-effect prediction etc.

Availability and implementation: The web service SPACE is available at http://www.bprc.ac.cn/space.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Computational Biology
Databases, Factual
Drug Discovery*
Drug Repositioning
Drug Therapy
Drug-Related Side Effects and Adverse Reactions
Internet
Models, Theoretical
Pharmaceutical Preparations / classification*
Software
Systems Integration

Substances

Pharmaceutical Preparations