ColdDTA: Utilizing data augmentation and attention-based feature fusion for drug-target binding affinity prediction

Abstract

Accurate prediction of drug-target affinity (DTA) plays a crucial role in drug discovery and development. Recently, deep learning methods have shown excellent predictive performance on randomly split public datasets. However, verifications are still required on this splitting method to reflect real-world problems in practical applications. And in a cold-start experimental setup, where drugs or proteins in the test set do not appear in the training set, the performance of deep learning models often significantly decreases. This indicates that improving the generalization ability of the models remains a challenge. To this end, in this study, we propose ColdDTA: using data augmentation and attention-based feature fusion to improve the generalization ability of predicting drug-target binding affinity. Specifically, ColdDTA generates new drug-target pairs by removing subgraphs of drugs. The attention-based feature fusion module is also used to better capture the drug-target interactions. We conduct cold-start experiments on three benchmark datasets, and the consistency index (CI) and mean square error (MSE) results on the Davis and KIBA datasets show that ColdDTA outperforms the five state-of-the-art baseline methods. Meanwhile, the results of area under the receiver operating characteristic (ROC-AUC) on the BindingDB dataset show that ColdDTA also has better performance on the classification task. Furthermore, visualizing the model weights allows for interpretable insights. Overall, ColdDTA can better solve the realistic DTA prediction problem. The code has been available to the public.