ProtAlign-ARG: antibiotic resistance gene characterization integrating protein language models and alignment-based scoring
Abstract The evolution and spread of antibiotic resistance pose a global health challenge. Whole genome and metagenomic sequencing offer a promising approach to monitoring the spread, but typical alignment-based approaches for antibiotic resistance gene (ARG) detection are inherently limited in the...
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| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-14545-4 |
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| Summary: | Abstract The evolution and spread of antibiotic resistance pose a global health challenge. Whole genome and metagenomic sequencing offer a promising approach to monitoring the spread, but typical alignment-based approaches for antibiotic resistance gene (ARG) detection are inherently limited in the ability to detect new variants. Large protein language models could present a powerful alternative but are limited by databases available for training. Here we introduce ProtAlign-ARG, a novel hybrid model combining a pre-trained protein language model and an alignment scoring-based model to expand the capacity for ARG detection from DNA sequencing data. ProtAlign-ARG learns from vast unannotated protein sequences, utilizing raw protein language model embeddings to improve the accuracy of ARG classification. In instances where the model lacks confidence, ProtAlign-ARG employs an alignment-based scoring method, incorporating bit scores and e-values to classify ARGs according to their corresponding classes of antibiotics. ProtAlign-ARG demonstrated remarkable accuracy in identifying and classifying ARGs, particularly excelling in recall compared to existing ARG identification and classification tools. We also extended ProtAlign-ARG to predict the functionality and mobility of ARGs, highlighting the model’s robustness in various predictive tasks. A comprehensive comparison of ProtAlign-ARG with both the alignment-based scoring model and the pre-trained protein language model demonstrated the superior performance of ProtAlign-ARG. |
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| ISSN: | 2045-2322 |