This study explores the application of generative Large Language Models (LLMs) in DNA sequence analysis, highlighting their advantages over encoder-based models like DNABERT2 and Nucleotide Transformer. While encoder models excel in classification, they struggle to integrate external textual information. In contrast, generative LLMs can incorporate domain knowledge, such as BLASTn annotations, to improve classification accuracy even without fine-tuning. We evaluate this capability on antimicrobial resistance (AMR) gene classification, comparing generative LLMs with encoder-based baselines. Results show that LLMs significantly enhance classification when supplemented with textual information. Additionally, we demonstrate their potential in DNA sequence generation, further expanding their applicability. Our findings suggest that LLMs offer a novel paradigm for integrating biological sequences with external knowledge, bridging gaps in traditional classification methods.

Antibiotic resistance identification is essential for public health, medical treatment, and drug development. Traditional sequence-based models struggle with accurate resistance prediction due to the lack of biological context. To address this, we propose an NLP-based model that integrates genetic sequences with structured textual annotations, including gene family classifications and resistance mechanisms. Our approach leverages pretrained language models for both genetic sequences and biomedical text, aligning biological metadata with sequence-based embeddings. We construct a novel dataset based on the Antibiotic Resistance Ontology (ARO), consolidating gene sequences with resistance-related textual information. Experiments show that incorporating domain knowledge significantly improves classification accuracy over sequence-only models, reducing reliance on exhaustive laboratory testing. By integrating genetic sequence processing with biomedical text understanding, our approach provides a scalable and interpretable solution for antibiotic resistance prediction.