DD-HGNN$^+$: Drug-Disease Association Prediction via General Hypergraph Neural Network With Hierarchical Contrastive Learning and Cross Attention Learning.

Abstract

The research on identifying drug-disease associations (DDAs) is widely used in scenarios such as drug development, clinical decision-making, and drug repurposing, holding significant biological and medical significance. Existing methods for drug-disease association prediction have achieved decent performance, they primarily rely on simplistic drug-disease association graphs or similarity graphs. These methods often struggle to capture the high-order correlations of complex multimodal data, limiting their ability to handle the complexity of data associations effectively. In addition, real drug-disease associations are highly sparse, posing a significant challenge to prediction accuracy. To tackle these issues, we propose a general hypergraph neural network framework for drug-disease association prediction based on hierarchical contrastive learning and cross-attention learning. It leverages hypergraph neural networks to learn representations of drugs and diseases carrying high-order correlations and strengthens representation quality using interactive attention learning and hierarchical contrastive learning. Meanwhile, the $\lambda$-weighted loss function is utilized to adapt to the high sparsity property of real drug-disease associations during model training and improve prediction performance. Extensive experiments demonstrate that DD-HGNN$^+$ surpasses other state-of-the-art methods in predicting drug-disease associations and further validation through case studies on Leukemia and Colorectal Neoplasms underscores its reliability.