Predicting Disease-Metabolite Associations Based on the Metapath Aggregation of Tripartite Heterogeneous Networks.

The exploration of the interactions between diseases and metabolites holds significant implications for the diagnosis and treatment of diseases. However, traditional experimental methods are time-consuming and costly, and current computational methods often overlook the influence of other biological entities on both. In light of these limitations, we proposed a novel deep learning model based on metapath aggregation of tripartite heterogeneous networks (MAHN) to explore disease-related metabolites. Specifically, we introduced microbes to construct a tripartite heterogeneous network and employed graph convolutional network and enhanced GraphSAGE to learn node features with metapath length 3. Additionally, we utilized node-level and semantic-level attention mechanisms, a more granular approach, to aggregate node features with metapath length 2. Finally, the reconstructed association probability is obtained by fusing features from different metapaths into the bilinear decoder. The experiments demonstrate that the proposed MAHN model achieved superior performance in five-fold cross-validation with Acc (91.85%), Pre (90.48%), Recall (93.53%), F1 (91.94%), AUC (97.39%), and AUPR (97.47%), outperforming four state-of-the-art algorithms. Case studies on two complex diseases, irritable bowel syndrome and obesity, further validate the predictive results, and the MAHN model is a trustworthy prediction tool for discovering potential metabolites. Moreover, deep learning models integrating multi-omics data represent the future mainstream direction for predicting disease-related biological entities.