Drug-target interaction prediction using ensemble learning and dimensionality reduction

Abstract

Experimental prediction of drug-target interactions is expensive, time-consuming and tedious. Fortunately, computational methods help narrow down the search space for interaction candidates to be further examined via wet-lab techniques. Nowadays, the number of attributes/features for drugs and targets, as well as the amount of their interactions, are increasing, making these computational methods inefficient or occasionally prohibitive. This motivates us to derive a reduced feature set for prediction. In addition, since ensemble learning techniques are widely used to improve the classification performance, it is also worthwhile to design an ensemble learning framework to enhance the performance for drug-target interaction prediction. In this paper, we propose a framework for drug-target interaction prediction leveraging both feature dimensionality reduction and ensemble learning. First, we conducted feature subspacing to inject diversity into the classifier ensemble. Second, we applied three different dimensionality reduction methods to the subspaced features. Third, we trained homogeneous base learners with the reduced features and then aggregated their scores to derive the final predictions. For base learners, we selected two classifiers, namely Decision Tree and Kernel Ridge Regression, resulting in two variants of ensemble models, EnsemDT and EnsemKRR, respectively. In our experiments, we utilized AUC (Area under ROC Curve) as an evaluation metric. We compared our proposed methods with various state-of-the-art methods under 5-fold cross validation. Experimental results showed EnsemKRR achieving the highest AUC (94.3%) for predicting drug-target interactions. In addition, dimensionality reduction helped improve the performance of EnsemDT. In conclusion, our proposed methods produced significant improvements for drug-target interaction prediction.

Keywords: Dimensionality reduction; Drug-target interaction prediction; Ensemble learning; Feature subspacing; Kernel ridge regression.