Dual-Network Cross-Learning for Metabolite-Disease Association Prediction.

In recent years, increasing evidence has demonstrated a close association between metabolites and various complex human diseases, providing valuable insights for disease diagnosis, treatment, and prevention. Although deep learning-based approaches have achieved certain success in predicting metabolic disease associations, challenges remain in enriching graph information and effectively integrating metabolic and disease features. To address these issues, this paper proposes a model named DCMDA, which extracts deep features of both metabolites and diseases using Dual-network Cross-learning for Metabolite-Disease Association prediction. DCMDA consists of three parts. The data processing module integrates similarity networks with association networks to construct a heterogeneous network. The feature extraction module extracts features from the metabolite-disease association network based on the non-negative matrix factorization method and from the heterogeneous network using graph autoencoder techniques. The feature fusion module combines the association matrix feature with the heterogeneous network feature through a Cross-Attention mechanism, thereby obtaining deep representations of metabolites and diseases. These features are then used to train the model to predict association scores between metabolites and diseases. Experimental results demonstrate that in 5-fold cross-validation, DCMDA achieves an area under the receiver operating characteristic curve (AUC) of 97.8% and an area under the precision-recall curve (AUPR) of 97.9%, outperforming state-of-the-art prediction methods.