CellAgent: LLM-Driven Multi-Agent Framework for Natural Language-Based Single-Cell Analysis

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) data analysis are pivotal for advancing biological research, enabling precise characterization of cellular heterogeneity. However, existing analysis approaches require extensive manual programming and complex tool integration, posing significant challenges for researchers. To address this, we introduce CellAgent, an autonomous, LLM-driven approach that performs end-to-end scRNA-seq and spatial transcriptomics data analysis through natural language interactions. CellAgent employs a multi-agent hierarchical decision-making framework, simulating a “deep-thinking” workflow to ensure that analytical steps are logically coherent and aligned with the overarching research goal. To further enhance its capabilities, we develop sc-Omni, a high-performance, expert-curated toolkit that consolidates essential tools for scRNA-seq and spatial transcriptomics analysis. Additionally, we introduce a self-reflective optimization mechanism, enabling automated, iterative refinement of results through specialized evaluation methods, effectively replacing traditional manual assessments. Benchmarking against human experts demonstrates that CellAgent achieves significant improvement in efficiency across multiple downstream applications while maintaining excellent performance comparable to existing approaches and preserving natural language interactions. By translating high-level scientific questions into optimized computational workflows, CellAgent represents a step toward a new, more accessible paradigm in bioinformatics, allowing researchers to perform complex data analyses autonomously. In lowering technical barriers, CellAgent serves to advance the democratization of the scientific discovery process in genomics.