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Single-cell omics arena: evaluation of large language models for automatic cell-type annotations on single-cell omics
Junhao Liu1, Siwei Xu1, Yongxian Wu2
1Department of Computer Science, University of California, Irvine, 6210 Donald Bren Hall, Irvine, CA 92697, United States.
Briefings in Bioinformatics
|November 24, 2025
Summary
Large language models (LLMs) can automate cell-type annotation from single-cell RNA sequencing data. A new benchmark, Single-cell Omics Arena, evaluates LLMs and introduces methods for enhanced accuracy and cross-modality applications.
Area of Science:
- Single-cell genomics
- Computational biology
- Artificial intelligence in biology
Background:
- Single-cell sequencing allows detailed tissue analysis but cell-type annotation is challenging.
- Automated methods are needed to overcome labor-intensive, expert-driven cell identification.
- Large language models (LLMs) show promise for extracting biological knowledge and automating annotations.
Purpose of the Study:
- To evaluate the efficacy of modern LLMs for automated cell-type annotation.
- To establish a comprehensive benchmark for assessing LLM performance on single-cell RNA sequencing (scRNA-seq) data.
- To develop advanced prompting techniques and cross-modality translation for improved annotation.
Main Methods:
- Compiled 11 scRNA-seq datasets and 1226 annotation tasks for benchmarking.
- Evaluated eight different LLMs on their cell-type annotation capabilities.
- Developed domain-specific chain-of-thought prompting and VAE-based cross-modality translation.
Main Results:
- Established the Single-cell Omics Arena benchmark for evaluating LLMs in cell-type annotation.
- Demonstrated LLMs' ability to perform automated cell-type annotation using interpretable features like gene names.
- Showcased enhanced accuracy via chain-of-thought prompting and extended applicability to non-RNA data using VAEs.
Conclusions:
- LLMs offer a powerful tool for automating cell-type annotation in scRNA-seq data.
- The Single-cell Omics Arena benchmark provides valuable insights into LLM performance.
- Cross-modality translation enables LLM application to diverse single-cell omics data types.

