DOI: 10.3390/life16061032 ISSN: 2075-1729

Responsible Use of Large Language Models in Microbial Genomics and Bioinformatics: A Life-Science Framework for Reliability, Reproducibility, and Risk-Aware Interpretation

Mia Yang Ang, Li Chen, Lanni Song, Leonard Lipovich, Siew Woh Choo

Large language models (LLMs) are increasingly adopted in life-science research for scientific writing, coding, literature synthesis, workflow troubleshooting, and preliminary data interpretation. In microbial genomics and bioinformatics, their appeal is clear because researchers routinely integrate genome annotations, antimicrobial resistance profiles, virulence determinants, taxonomic assignments, microbiome outputs, workflow scripts, and primary literature. Yet this domain also highlights major risks, including hallucinated biological claims, inaccurate citations, irreproducible code, unsupported genotype-to-phenotype inference, and inappropriate clinical or public health framing. This narrative review examines responsible LLM use in microbial genomics as a representative life-science setting where interpretation depends on database provenance, validated workflows, expert assessment, and reproducible evidence chains. It considers applications in genome annotation, antimicrobial resistance interpretation, virulence analysis, microbiome and metagenomics workflows, coding support, and scientific writing. The review further presents MicrobeGuardGPT as a conceptual reliability framework for assessing LLM-assisted microbial genomics outputs before scientific, clinical, or public health use. By connecting task domains, evidence verification, expert validation, and reliability classification, the framework supports risk-aware LLM integration in bioinformatics. Responsible implementation will require domain-specific benchmarks, curated database linkage, transparent reporting, reproducible workflows, human oversight, and governance standards tailored to biological interpretation across research, diagnostic, surveillance, outbreak-response, educational, and translational contexts.

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