PhageHost-GNN: novelty-aware and locally adaptable strain-level Klebsiella-phage prediction

Abstract

Interest in bacteriophages as alternative treatments for bacterial infections has grown amid the ongoing crisis of multidrug resistance. However, their narrow host range makes it labor-intensive to identify matching phages for bacterial isolates using conventional experimental methods. Although existing computational models based on biomolecular features have shown promise for phage-host matching, the performance of alternative model settings, including data embeddings, across datasets with different degrees of novelty remains underexplored. This study introduces PhageHost-GNN, a novelty-aware framework using routed models to predict strain-level Klebsiella-phage interactions, evaluated under three clinical scenarios. Using multiple embedding models to encode sequence, structural, and genomic-context features, the framework achieved AUPRCs reaching 0.784, 0.731, and 0.642 in host-unseen, phage-unseen, and both-unseen in silico evaluations, respectively. Benchmarks on experimentally validated datasets showed the clearest advantage over fixed embeddings when both hosts and phages were new to the trained model. In addition to direct inference and de novo training, the framework further implements a fine-tuning pipeline to adapt existing models to local custom datasets while reducing model-training time. Overall, PhageHost-GNN provides a flexible framework for model selection, evaluation, and local adaptation in practical phage-therapy screening. New aspects/highlights Novelty-aware and multi-model routing for phage-host prediction. Implementation of three clinically practical inference settings. Flexible clinical adaptation via de novo training or fine-tuning based on the novelty of local strain datasets.