PhaGO：通过整合基因组上下文实现噬菌体的蛋白质功能注释
PhaGO: Protein function annotation for bacteriophages by integrating the genomic context
AI总结：
针对噬菌体蛋白功能注释难的问题，研究提出PhaGO工具，结合蛋白基础模型嵌入与Transformer捕获基因组上下文信息，在分化及罕见功能蛋白注释上优于现有方法，还可注释无同源搜索结果的蛋白并鉴定出潜在穿孔素。
摘要：
噬菌体是靶向细菌的病毒，在微生物生态中发挥着关键作用。噬菌体蛋白对于理解噬菌体生物学（如病毒感染、复制和进化）至关重要。尽管通过宏基因组测序已鉴定出大量新噬菌体，但其中许多噬菌体的蛋白质功能注释十分有限。噬菌体蛋白的准确功能注释存在若干挑战，包括其固有的多样性以及已注释蛋白的稀缺性。现有工具尚未充分利用噬菌体的独特特性来进行蛋白质功能注释。在本研究中，我们利用噬菌体基因组的模块化基因组结构，提出了一种新型噬菌体蛋白质功能注释工具。通过采用最新蛋白质基础模型的嵌入向量和Transformer来捕获噬菌体基因组中蛋白质之间的上下文信息，PhaGO在注释分化蛋白和具有罕见功能的蛋白方面分别超越了当前最优方法6.78%和13.05%。PhaGO能够注释缺乏同源性搜索结果的蛋白质，这对于表征快速积累的噬菌体基因组至关重要。我们通过在噬菌体中鉴定出688种潜在的holin（穿孔素）证明了PhaGO的实用性，这些蛋白与已知holin表现出高度的结构保守性。研究结果显示了PhaGO拓展我们对新发现噬菌体认知的潜力。
英文摘要：
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.
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