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Updated: Sep 13, 2025

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GeneAgent: self-verification language agent for gene-set analysis using domain databases.

Zhizheng Wang1, Qiao Jin1, Chih-Hsuan Wei1

  • 1Division of Intramural Research, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.

Nature Methods
|July 28, 2025
PubMed
Summary
This summary is machine-generated.

GeneAgent, an AI tool, enhances gene-set analysis by reducing factual errors. It autonomously verifies information against biological databases, outperforming existing models like GPT-4 for accurate functional gene descriptions.

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Artificial Intelligence in Genomics

Background:

  • Gene-set analysis identifies biological mechanisms for gene groups.
  • Large language models (LLMs) show potential for gene function description but risk factual inaccuracies (hallucinations).

Purpose of the Study:

  • To develop and evaluate GeneAgent, an LLM-based AI agent designed to reduce hallucinations in gene-set analysis.
  • To improve the accuracy and comprehensiveness of functional descriptions for gene sets.

Main Methods:

  • GeneAgent autonomously interacts with biological databases to verify its generated gene set descriptions.
  • LLM-based AI agent for gene-set analysis.
  • Evaluation using 1,106 diverse gene sets and novel gene sets from mouse melanoma cell lines.

Main Results:

  • GeneAgent demonstrated significantly higher accuracy compared to GPT-4 across 1,106 evaluated gene sets.
  • Expert review confirmed GeneAgent's superior relevance and comprehensiveness for novel gene sets.
  • GeneAgent effectively reduces hallucinations in LLM-generated functional descriptions.

Conclusions:

  • GeneAgent offers a more accurate and reliable approach to gene-set analysis compared to existing LLMs.
  • This AI agent expedites biological knowledge discovery by providing validated functional insights.
  • GeneAgent represents a significant advancement in applying AI for biological mechanism identification.