AttenSyn: An Attention-Based Deep Graph Neural Network for Anticancer Synergistic Drug Combination Prediction.

Identifying synergistic drug combinations is fundamentally important to treat a variety of complex diseases while avoiding severe adverse drug-drug interactions. Although several computational methods have been proposed, they highly rely on handcrafted feature engineering and cannot learn better interactive information between drug pairs, easily resulting in relatively low performance. Recently, deep-learning methods, especially graph neural networks, have been widely developed in this area and demonstrated their ability to address complex biological problems. In this study, we proposed AttenSyn, an attention-based deep graph neural network for accurately predicting synergistic drug combinations. In particular, we adopted a graph neural network module to extract high-latent features based on the molecular graphs only and exploited the attention-based pooling module to learn interactive information between drug pairs to strengthen the representations of drug pairs. Comparative results on the benchmark datasets demonstrated that our AttenSyn performs better than the state-of-the-art methods in the prediction of anticancer synergistic drug combinations. Additionally, to provide good interpretability of our model, we explored and visualized some crucial substructures in drugs through attention mechanisms. Furthermore, we also verified the effectiveness of our proposed AttenSyn on two cell lines by visualizing the features of drug combinations learnt from our model, exhibiting satisfactory generalization ability.