Accurate prediction of virulence factors using pre-train protein language model and ensemble learning.

Abstract

Background: As bacterial pathogens develop increasing resistance to antibiotics, strategies targeting virulence factors (VFs) have emerged as a promising and effective approach for treating bacterial infections. Existing methods mainly relied on sequence similarity, and remote homology relationships cannot be discovered by sequence analysis alone.

Results: To address this limitation, we developed a protein language model and ensemble learning approach for VF identification (PLMVF). Specifically, we extracted features from protein sequences using ESM-2 and their three-dimensional (3D) structures using ESMFold. We calculated the true TM-score of the proteins based on their 3D structures and trained a TM-predictor model to predict structural similarity, thereby capturing hidden remote homology information within the sequences. Subsequently, we concatenated the sequence-level features extracted by ESM-2 with the predicted TM-score features to form a comprehensive feature set for prediction. Extensive experimental validation demonstrated that PLMVF achieved an accuracy (ACC) of 86.1%, significantly outperforming existing models across multiple evaluation metrics. This study provided an ideal tool for identifying novel targets in the development of anti-virulence therapies, offering promise for the effective prevention and control of pathogenic bacterial infections.

Conclusions: The proposed PLMVF model offers an efficient computational approach for VF identification.