文章基本信息

标题：Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations
本地全文：下载
作者：Santiago Vilar ; George Hripcsak
期刊名称：Journal of Cheminformatics
印刷版ISSN：1758-2946
电子版ISSN：1758-2946
出版年度：2016
卷号：8
期号：1
页码：35
DOI：10.1186/s13321-016-0147-1
语种：English
出版社：BioMed Central
摘要：Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.
关键词：3D molecular structure ; Pharmacophoric ; Target ; Adverse effect