Graph Neural Network-Based Modeling with Subcategory Exploration for Drug Repositioning

Drug repositioning is a cost-effective approach to identifying new indications for existing drugs by predicting their associations with new diseases or symptoms. Recently, deep learning-based models have become the mainstream for drug repositioning. Existing methods typically regard the drug-repositioning task as a binary classification problem to find the new drug–disease associations. However, drug–disease associations may encompass some potential subcategories that can be used to enhance the classification performance. In this paper, we propose a prototype-based subcategory exploration (PSCE) model to guide the model learned with the information of a potential subcategory for drug repositioning. To achieve this, we first propose a prototype-based feature-enhancement mechanism (PFEM) that uses clustering centroids as the attention to enhance the drug–disease features by introducing subcategory information to improve the association prediction. Second, we introduce the drug–disease dual-task classification head (D3TC) of the model, which consists of a traditional binary classification head and a subcategory-classification head to learn with subcategory exploration. It leverages finer-grained pseudo-labels of subcategories to introduce additional knowledge for precise drug–disease association classification. In this study, we conducted experiments on four public datasets to compare the proposed PSCE with existing state-of-the-art approaches and our PSCE achieved a better performance than the existing ones. Finally, the effectiveness of the PFEM and D3TC was demonstrated using ablation studies.