Drug-target interaction prediction by integrating chemical, genomic, functional and pharmacological data

In silico prediction of unknown drug-target interactions (DTIs) has become a popular tool for drug repositioning and drug development. A key challenge in DTI prediction lies in integrating multiple types of data for accurate DTI prediction. Although recent studies have demonstrated that genomic, chemical and pharmacological data can provide reliable information for DTI prediction, it remains unclear whether functional information on proteins can also contribute to this task. Little work has been developed to combine such information with other data to identify new interactions between drugs and targets. In this paper, we introduce functional data into DTI prediction and construct biological space for targets using the functional similarity measure. We present a probabilistic graphical model, called conditional random field (CRF), to systematically integrate genomic, chemical, functional and pharmacological data plus the topology of DTI networks into a unified framework to predict missing DTIs. Tests on two benchmark datasets show that our method can achieve excellent prediction performance with the area under the precision-recall curve (AUPR) up to 94.9. These results demonstrate that our CRF model can successfully exploit heterogeneous data to capture the latent correlations of DTIs, and thus will be practically useful for drug repositioning. Supplementary Material is available at http://iiis.tsinghua.edu.cn/~compbio/papers/psb2014/psb2014_sm.pdf.