MathEagle: Accurate prediction of drug-drug interaction events via multi-head attention and heterogeneous attribute...

Drug-drug interaction events influence the effectiveness of drug combinations and can lead to unexpected side effects or exacerbate underlying diseases, jeopardizing patient prognosis. Most existing methods are restricted to predicting whether two drugs interact or the type of drug-drug interactions, while very few studies endeavor to predict the specific risk levels of side effects of drug combinations.

In this study, we propose MathEagle, a novel approach to predict accurate risk levels of drug combinations based on multi-head attention and heterogeneous attribute graph learning. Initially, we model drugs and three distinct risk levels between drugs as a heterogeneous information graph. Subsequently, behavioral and chemical structure features of drugs are utilized by message passing neural networks and graph embedding algorithms, respectively. Ultimately, MathEagle employs heterogeneous graph convolution and multi-head attention mechanisms to learn efficient latent representations of drug nodes and estimates the risk levels of pairwise drugs in an end-to-end manner.

To assess the effectiveness and robustness of the model, five-fold cross-validation, ablation experiments, and case studies were conducted. MathEagle achieved an accuracy of 85.85 % and an AUC of 0.9701 on the drug risk level prediction task and is superior to all comparative models. The MathEagle predictor is freely accessible at http://120.77.11.78/MathEagle/.

The experimental results indicate that MathEagle can function as an effective tool for predicting accurate risk of drug combinations, aiding in guiding clinical medication, and enhancing patient outcomes.