MASMDDI: multi-layer adaptive soft-mask graph neural network for drug-drug interaction prediction.

Accurately predicting Drug-Drug Interaction (DDI) is a critical and challenging aspect of the drug discovery process, particularly in preventing adverse reactions in patients undergoing combination therapy. However, current DDI prediction methods often overlook the interaction information between chemical substructures of drugs, focusing solely on the interaction information between drugs and failing to capture sufficient chemical substructure details. To address this limitation, we introduce a novel DDI prediction method: Multi-layer Adaptive Soft Mask Graph Neural Network (MASMDDI). Specifically, we first design a multi-layer adaptive soft mask graph neural network to extract substructures from molecular graphs. Second, we employ an attention mechanism to mine substructure feature information and update latent features. In this process, to optimize the final feature representation, we decompose drug-drug interactions into pairwise interaction correlations between the core substructures of each drug. Third, we use these features to predict the interaction probabilities of DDI tuples and evaluate the model using real-world datasets. Experimental results demonstrate that the proposed model outperforms state-of-the-art methods in DDI prediction. Furthermore, MASMDDI exhibits excellent performance in predicting DDIs of unknown drugs in two tasks that are more aligned with real-world scenarios. In particular, in the transductive scenario using the DrugBank dataset, the ACC and AUROC and AUPRC scores of MASMDDI are 0.9596, 0.9903, and 0.9894, which are 2% higher than the best performing baseline.