A GraphSAGE-based model with fingerprints only to predict drug-drug interactions

Abstract

<abstract> <p>Drugs are an effective way to treat various diseases. Some diseases are so complicated that the effect of a single drug for such diseases is limited, which has led to the emergence of combination drug therapy. The use multiple drugs to treat these diseases can improve the drug efficacy, but it can also bring adverse effects. Thus, it is essential to determine drug-drug interactions (DDIs). Recently, deep learning algorithms have become popular to design DDI prediction models. However, most deep learning-based models need several types of drug properties, inducing the application problems for drugs without these properties. In this study, a new deep learning-based model was designed to predict DDIs. For wide applications, drugs were first represented by commonly used properties, referred to as fingerprint features. Then, these features were perfectly fused with the drug interaction network by a type of graph convolutional network method, GraphSAGE, yielding high-level drug features. The inner product was adopted to score the strength of drug pairs. The model was evaluated by 10-fold cross-validation, resulting in an AUROC of 0.9704 and AUPR of 0.9727. Such performance was better than the previous model which directly used drug fingerprint features and was competitive compared with some other previous models that used more drug properties. Furthermore, the ablation tests indicated the importance of the main parts of the model, and we analyzed the strengths and limitations of a model for drugs with different degrees in the network. This model identified some novel DDIs that may bring expected benefits, such as the combination of PEA and cannabinol that may produce better effects. DDIs that may cause unexpected side effects have also been discovered, such as the combined use of WIN 55,212-2 and cannabinol. These DDIs can provide novel insights for treating complex diseases or avoiding adverse drug events.</p> </abstract>