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.