An Ensemble Learning-Based Method for Inferring Drug-Target Interactions Combining Protein Sequences and Drug Fingerprints

Abstract

Identifying the interactions of the drug-target is central to the cognate areas including drug discovery and drug reposition. Although the high-throughput biotechnologies have made tremendous progress, the indispensable clinical trials remain to be expensive, laborious, and intricate. Therefore, a convenient and reliable computer-aided method has become the focus on inferring drug-target interactions (DTIs). In this research, we propose a novel computational model integrating a pyramid histogram of oriented gradients (PHOG), Position-Specific Scoring Matrix (PSSM), and rotation forest (RF) classifier for identifying DTIs. Specifically, protein primary sequences are first converted into PSSMs to describe the potential biological evolution information. After that, PHOG is employed to mine the highly representative features of PSSM from multiple pyramid levels, and the complete describers of drug-target pairs are generated by combining the molecular substructure fingerprints and PHOG features. Finally, we feed the complete describers into the RF classifier for effective prediction. The experiments of 5-fold Cross-Validations (CV) yield mean accuracies of 88.96%, 86.37%, 82.88%, and 76.92% on four golden standard data sets (enzyme, ion channel, G protein-coupled receptors (GPCRs), and nuclear receptor, respectively). Moreover, the paper also conducts the state-of-art light gradient boosting machine (LGBM) and support vector machine (SVM) to further verify the performance of the proposed model. The experimental outcomes substantiate that the established model is feasible and reliable to predict DTIs. There is an excellent prospect that our model is capable of predicting DTIs as an efficient tool on a large scale.