DTIRF: Predicting Drug-Target Interactions Based on Improved Rotation Forest from Drug Molecular Structure and Protein Sequence

Abstract

Background: The identification and prediction of Drug-Target Interaction (DTI) is the basis for screening drug candidates, which plays a vital role in the development of innovative drugs. However, due to the time-consuming and high cost constraints of biological experimental methods, traditional drug target identification technologies are often difficult to develop on a large scale. Therefore, in silico methods are urgently needed to predict drug-target interactions in a genome-wide manner. Results: In this article, we design a new in silico approach, named DTIRF, to predict the DTI combine feature weighted Rotation Forest (FwRF) classifier with protein amino acids information. More specifically, we first use Position-Specific Score Matrix (PSSM) to numerically convert protein sequences and utilize Pseudo Position-Specific Score Matrix (PsePSSM) to extract their features. Then a unified digital descriptor is formed by combining molecular fingerprints representing drug information. Finally, the feature weighted rotation forest is applied to implement on Enzyme, Ion Channel, GPCR, and Nuclear Receptor data sets. The results of the five-fold cross-validation experiment show that the prediction accuracy of this approach reaches 91.68%, 88.11%, 84.72% and 78.33% on four benchmark data sets, respectively. To further validate the performance of the DTIRF, we compare it with other excellent methods and Support Vector Machine (SVM) model. In addition, 7 of the 10 highest predictive scores in predicting novel DTIs were validated by relevant databases. Conclusions: The experimental results of cross-validation indicated that DTIRF is feasible in predicting the relationship among drugs and target, and can provide help for the discovery of new candidate drugs.