LLM4Cell: Taxonomy and Evaluation of LLM and Agentic Models for Single-Cell Biology

摘要

Large language models (LLMs) and emerging agentic frameworks are beginning to influence single-cell biology by enabling natural-language interfaces, generative annotation, and multimodal data integration. However, progress remains fragmented across data modalities, model families, and evaluation practices. LLM4Cell presents a unified survey of 58 foundation and agentic models developed for single-cell research, spanning RNA, ATAC, multi-omic, and spatial modalities. We organize these methods into five families foundation, text-bridge, spatial/multimodal, epigenomic, and agentic and map them to eight key analytical tasks, including annotation, trajectory inference, perturbation modeling, and drug-response prediction. Drawing on over 40 public datasets, we analyze benchmark coverage, data diversity, and ethical or scalability constraints, and synthesize reported capabilities across ten domain-level dimensions related to biological grounding, multimodal alignment, fairness, privacy, and interpretability. By explicitly linking datasets, modeling paradigms, and evaluation domains, LLM4Cell provides an integrated perspective on language-driven single-cell analysis and highlights open challenges in standardization, interpretability, and trustworthy model development.