title: Genome-scale screening of drug-target associations relevant to Ki using a chemogenomics approach.
abstract: The identification of interactions between drugs and target proteins plays a key role in genomic drug discovery. In the present study, the quantitative binding affinities of drug-target pairs are differentiated as a measurement to define whether a drug interacts with a protein or not, and then a chemogenomics framework using an unbiased set of general integrated features and random forest (RF) is employed to construct a predictive model which can accurately classify drug-target pairs. The predictability of the model is further investigated and validated by several independent validation sets. The built model is used to predict drug-target associations, some of which were confirmed by comparing experimental data from public biological resources. A drug-target interaction network with high confidence drug-target pairs was also reconstructed. This network provides further insight for the action of drugs and targets. Finally, a web-based server called PreDPI-Ki was developed to predict drug-target interactions for drug discovery. In addition to providing a high-confidence list of drug-target associations for subsequent experimental investigation guidance, these results also contribute to the understanding of drug-target interactions. We can also see that quantitative information of drug-target associations could greatly promote the development of more accurate models. The PreDPI-Ki server is freely available via: http://sdd.whu.edu.cn/dpiki.
authors.affiliation: Research Center of Modernization of Traditional Chinese Medicines, Central South University, Changsha, PR China.
authors.forename: Dong-Sheng
authors.initials: DS
authors.lastname: Cao
authors.forename: Yi-Zeng
authors.initials: YZ
authors.lastname: Liang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Deng
authors.forename: Qian-Nan
authors.initials: QN
authors.lastname: Hu
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Qing-Song
authors.initials: QS
authors.lastname: Xu
authors.forename: Guang-Hua
authors.initials: GH
authors.lastname: Zhou
authors.forename: Liu-Xia
authors.initials: LX
authors.lastname: Zhang
authors.forename: Zi-xin
authors.initials: ZX
authors.lastname: Deng
authors.forename: Shao
authors.initials: S
authors.lastname: Liu
mesh_terms: D004353:Drug Evaluation, Preclinical / Q000379:methods*; D023281:Genomics / Q000379:methods*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011336:Probability; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D012372:ROC Curve
chemical_list: D004364:Pharmaceutical Preparations; D011506:Proteins