Drug-target interaction prediction using reliable negative samples and effective feature selection methods

Abstract

Machine learning-based approaches in the field of drug discovery have dramatically reduced the time and cost of the laboratory process of detecting potential drug-target interactions (DTIs). Standard binary classifiers require both positive and negative samples in the training and validation phases. One of the major challenges in the DTI context is the lack of access to non-interacting pairs as negative samples in the learning process. Many recent studies in this field have randomly selected negative samples from unlabeled drug-target pairs. Therefore, due to the probability of the presence of unknown positive samples in a set considered as negative samples, the model results may be affected and appear with a high rate of false positive. In this study, an algorithm called Reliable Non-Interacting Drug-Target Pairs (RNIDTP) is proposed to select reliable negative samples and an efficient algorithm to select relevant features for drug-target interaction prediction. To validate the performance of the proposed RNIDTP algorithm in the selection of negative samples, a benchmark drug-target interactions dataset is used. The results demonstrate the superiority of the proposed algorithm compared with other algorithms in most cases. The results also indicate that by using an appropriate algorithm for the selection of negative samples, the performance of the learning process is significantly increased compared to random selection.