The identification of drug-target interactions (DTIs) plays a crucial role in drug discovery. However, the traditional high-throughput techniques based on clinical trials are costly, cumbersome, and time-consuming for identifying DTIs. Hence, new intelligent computational methods are urgently needed to surmount these defects in predicting DTIs. In this paper, we propose a novel computational method that combines position-specific scoring matrix (PSSM), elastic net based sparse features extraction, and rotation forest (RF) classifier. Specifically, we converted each protein primary sequence into PSSM, which contains biological evolutionary information. Then we extract the hidden sparse feature descriptors in PSSM by elastic net based sparse feature extraction method (ESFE). After that, we fuse them with the features of drug, which are represented by molecular fingerprints. Finally, rotation forest classifier works on detecting the potential drug-target interactions. When performing the proposed method by the experiments of fivefold cross validation (CV) on enzyme, ion channel, G protein-coupled receptors (GPCRs), and nuclear receptor datasets, this method achieves average accuracies of 90.32%, 88.91%, 80.65%, and 79.73%, respectively. We also compared the proposed model with the state-of-the-art support vector machine (SVM) classifier and other effective methods on the same datasets. The comparison results distinctly indicate that the proposed model possesses the efficient and robust ability to predict DTIs. We expect that the new model will be able to take effects on predicting massive DTIs.
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