PhaGO: Protein function annotation for bacteriophages by integrating the genomic context

TL;DR

PhaGO is a novel tool that leverages genomic context and advanced embedding models to improve protein function annotation in bacteriophages, especially for diverged and uncommon proteins, aiding in understanding phage biology.

Contribution

This work introduces PhaGO, a new annotation method that integrates genomic modularity and Transformer-based embeddings to enhance phage protein function prediction.

Findings

Outperforms existing methods with 6.78% and 13.05% improvements in annotating diverged and uncommon proteins.

Can annotate proteins without homology search results, addressing a key challenge in phage genomics.

Successfully identified 688 potential holins, demonstrating practical utility.

Abstract

Bacteriophages are viruses that target bacteria, playing a crucial role in microbial ecology. Phage proteins are important in understanding phage biology, such as virus infection, replication, and evolution. Although a large number of new phages have been identified via metagenomic sequencing, many of them have limited protein function annotation. Accurate function annotation of phage proteins presents several challenges, including their inherent diversity and the scarcity of annotated ones. Existing tools have yet to fully leverage the unique properties of phages in annotating protein functions. In this work, we propose a new protein function annotation tool for phages by leveraging the modular genomic structure of phage genomes. By employing embeddings from the latest protein foundation models and Transformer to capture contextual information between proteins in phage genomes, PhaGO surpasses state-of-the-art methods in annotating diverged proteins and proteins with uncommon functions by 6.78% and 13.05% improvement, respectively. PhaGO can annotate proteins lacking homology search results, which is critical for characterizing the rapidly accumulating phage genomes. We demonstrate the utility of PhaGO by identifying 688 potential holins in phages, which exhibit high structural conservation with known holins. The results show the potential of PhaGO to extend our understanding of newly discovered phages.