HBFormer: a single-stream framework based on hybrid attention mechanism for identification of human-virus protein–protein interactions

Motivation: Exploring human-virus protein–protein interactions (PPIs) is crucial for unraveling the underlying pathogenic mechanisms of viruses. Limitations in the coverage and scalability of high-throughput approaches have impeded the identification of certain key interactions. Current popular computational methods adopt a two-stream pipeline to identify PPIs, which can only achieve relation modeling of protein pairs at the classification phase. However, the fitting capacity of the classifier is insufficient to comprehensively mine the complex interaction patterns between protein pairs. Results: In this study, we propose a pioneering single-stream framework HBFormer that combines hybrid attention mechanism and multimodal feature fusion strategy for identifying human-virus PPIs. The Transformer architecture based on hybrid attention can bridge the bidirectional information flows between human protein and viral protein, thus unifying joint feature learning and relation modeling of protein pairs. The experimental results demonstrate that HBFormer not only achieves superior performance on multiple human-virus PPI datasets but also outperforms 5 other state-of-the-art human-virus PPI identification methods. Moreover, ablation studies and scalability experiments further validate the effectiveness of our single-stream framework.