MAMGN-HTI: A Graph Neural Network Model with Metapath and Attention Mechanisms for Hyperthyroidism Herb-Target Interaction Prediction.

The accurate prediction of herb-target interactions is essential for the modernization of traditional Chinese medicine (TCM) and the advancement of drug discovery. Nonetheless, the inherent complexity of herbal compositions and diversity of molecular targets render experimental validation both time-consuming and labor-intensive. We propose a graph neural network model, MAMGN-HTI, which integrates metapaths with attention mechanisms. A heterogeneous graph consisting of herbs, efficacies, ingredients, and targets is constructed, where semantic metapaths capture latent relationships among nodes. An attention mechanism is employed to dynamically assign weights, thereby emphasizing the most informative metapaths. In addition, ResGCN and DenseGCN architectures are combined with cross-layer skip connections to improve feature propagation and enable effective feature reuse. Experiments show that MAMGN-HTI outperforms several state-of-the-art methods across multiple metrics, exhibiting superior accuracy, robustness, and generalizability in HTI prediction and candidate drug screening. Validation against literature and databases further confirms the model's predictive reliability. The model also successfully identified herbs with potential therapeutic effects for hyperthyroidism, including Vinegar-processed Bupleuri Radix (Cu Chaihu), Prunellae Spica (Xiakucao), and Processed Cyperi Rhizoma (Zhi Xiangfu). MAMGN-HTI provides a reliable computational framework and theoretical foundation for applying TCM in hyperthyroidism treatment, providing mechanistic insights while improving research efficiency and resource utilization.