Abstract
Antibiotic resistance poses a significant threat to global health, making the development of alternative strategies to combat bacterial pathogens increasingly urgent. One such promising approach is the strategic use of bacteriophages (or phages) to specifically target and eradicate antibiotic-resistant bacteria. Phages, being among the most prevalent life forms on Earth, play a critical role in maintaining ecological balance by regulating bacterial communities and driving genetic diversity. Accurate prediction of phage hosts is essential for successfully applying phage therapy. However, existing prediction models may not fully encapsulate the complex dynamics of phage-host interactions in diverse microbial environments, indicating a need for improved accuracy through more sophisticated modeling techniques. In response to this challenge, this study introduces a novel phage-host prediction model, PHPGAT, which leverages a multimodal heterogeneous knowledge graph with the advanced GATv2 (Graph Attention Network v2) framework. The model first constructs a multimodal heterogeneous knowledge graph by integrating phage-phage, host-host, and phage-host interactions to capture the intricate connections between biological entities. GATv2 is then employed to extract deep node features and learn dynamic interdependencies, generating context-aware embeddings. Finally, an inner product decoder is designed to compute the likelihood of interaction between a phage and host pair based on the embedding vectors produced by GATv2. Evaluation results using two datasets demonstrate that PHPGAT achieves precise phage host predictions and outperforms other models. PHPGAT is available at https://github.com/ZhaoZMer/PHPGAT.