SEGT-GO: a graph transformer method based on PPI serialization and explanatory artificial intelligence for protein function prediction

Background: A massive amount of protein sequences have been obtained, but their functions remain challenging to discern. In recent research on protein function prediction, Protein-Protein Interaction (PPI) Networks have played a crucial role. Uncovering potential function relationships between distant proteins within PPI networks is essential for improving the accuracy of protein function prediction. Most current studies attempt to capture these distant relationships by stacking graph network layers, but performance gains diminish as the number of layers increases. Results: To further explore the potential functional relationships between multi-hop proteins in PPI networks, this paper proposes SEGT-GO, a Graph Transformer method based on PPI multi-hop neighborhood Serialization and Explainable artificial intelligence for large-scale multispecies protein function prediction. The multi-hop neighborhood serialization maps multi-hop information in the PPI Network into serialized feature embeddings, enabling the Graph Transformer to learn deeper functional features within the PPI Network. Based on game theory, the SHAP eXplainable Artificial Intelligence (XAI) framework optimizes model input and filters out feature noise, enhancing model performance. Conclusions: Compared to the advanced network method DeepGraphGO, SEGT-GO achieves more competitive results in standard large-scale datasets and superior results on small ones, validating its ability to extract functional information from deep proteins. Furthermore, SEGT-GO achieves superior results in cross-species learning and prediction of the functions of unseen proteins, further proving the method’s strong generalization.