Predicting drug-drug interactions: A deep learning approach with GCN-based collaborative filtering

초록

The use of combination drugs among patients is increasing due to effectiveness compared to monotherapies. However, healthcare providers should continue to be concerned about the potential risks associated with patient safety arising from drug-drug interactions (DDIs) when they use combination drugs. Whereas direct physicochemical interactions contribute to certain cases of DDIs, the majority of DDIs occur because one drug modulates enzymes, such as cytochrome P450, responsible for metabolizing another drug. Therefore, drugs that interact with the same family drugs are more likely to interact with each other by mediating specific enzymes. Adapted from techniques used to recommend users with similar interests, we introduce an AI recommendation model with graph convolutional network (GCN) and collaborative filtering that analyzes the connectivity of interacting drugs rather than their chemical structures. This approach deviates from typical classification models by not requiring sampling of undefined interactions as negative samples, allowing the prediction of potential interactions for all unknown drug pairs, circumventing the challenges associated with selecting negative interactions and data imbalance. Our methodology used the DrugBank database (version 5.1.9 released on January 3, 2022), encompassing 4,072 drugs and 1,391,790 drug pairs with interactions. Furthermore, the robustness of the model was verified through a 5-fold validation and external data validation using TWOSIDES data. Notably, our model's efficacy is established solely through the exploitation of DDI reports, offering a versatile framework capable of accurately predicting interactions among diverse drug types. The source code for this project is distributed on GitHub (https://github.com/yeonuk-Jeong/DDI-OCF).

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