Predicting antibiotic resistance genes and bacterial phenotypes based on protein language models

Introduction Antibiotic resistance is emerging as a critical global public health threat. The precise prediction of bacterial antibiotic resistance genes (ARGs) and phenotypes is essential to understand resistance mechanisms and guide clinical antibiotic use. Although high-throughput DNA sequencing provides a foundation for identification, current methods lack precision and often require manual intervention. Methods We developed a novel deep learning model for ARG prediction by integrating bacterial protein sequences using two protein language models, ProtBert-BFD and ESM-1b. The model further employs data augmentation techniques and Long Short-Term Memory (LSTM) networks to enhance feature extraction and classification performance. Results The proposed model demonstrated superior performance compared to existing methods, achieving higher accuracy, precision, recall, and F1-score. It significantly reduced both false negative and false positive predictions in identifying ARGs, providing a robust computational tool for reliable gene-level resistance detection. Moreover, the model was successfully applied to predict bacterial resistance phenotypes, demonstrating its potential for clinical applicability. Discussion This study presents an accurate and automated approach for predicting antibiotic resistance genes and phenotypes, reducing the need for manual verification. The model offers a powerful technical tool that can support clinical decision-making and guide antibiotic use, thereby addressing an urgent need in the fight against antimicrobial resistance.