PlasGO: enhancing GO-based function prediction for plasmid-encoded proteins based on genetic structure.

Background: Plasmid, as a mobile genetic element, plays a pivotal role in facilitating the transfer of traits, such as antimicrobial resistance, among the bacterial community. Annotating plasmid-encoded proteins with the widely used Gene Ontology (GO) vocabulary is a fundamental step in various tasks, including plasmid mobility classification. However, GO prediction for plasmid-encoded proteins faces 2 major challenges: the high diversity of functions and the limited availability of high-quality GO annotations.

Results: In this study, we introduce PlasGO, a tool that leverages a hierarchical architecture to predict GO terms for plasmid proteins. PlasGO utilizes a powerful protein language model to learn the local context within protein sentences and a BERT model to capture the global context within plasmid sentences. Additionally, PlasGO allows users to control the precision by incorporating a self-attention confidence weighting mechanism. We rigorously evaluated PlasGO and benchmarked it against 7 state-of-the-art tools in a series of experiments. The experimental results collectively demonstrate that PlasGO has achieved commendable performance. PlasGO significantly expanded the annotations of the plasmid-encoded protein database by assigning high-confidence GO terms to over 95% of previously unannotated proteins, showcasing impressive precision of 0.8229, 0.7941, and 0.8870 for the 3 GO categories, respectively, as measured on the novel protein test set.

Conclusions: PlasGO, a hierarchical tool incorporating protein language models and BERT, significantly expanded plasmid protein annotations by predicting high-confidence GO terms. These annotations have been compiled into a database, which will serve as a valuable contribution to downstream plasmid analysis and research.