LLM4Cell: A Survey of Large Language and Agentic Models for Single-Cell
  Biology
Authors: name: Sajib Acharjee Dip; name: Adrika Zafor; name: Bikash Kumar Paul; name: Uddip Acharjee Shuvo; name: Muhit Islam Emon; name: Xuan Wang; name: Liqing Zhang
Published: 2025-10-09 05:12:09

Abstract: Large language models (LLMs) and emerging agentic frameworks are beginning to
transform single-cell biology by enabling natural-language reasoning,
generative annotation, and multimodal data integration. However, progress
remains fragmented across data modalities, architectures, and evaluation
standards. LLM4Cell presents the first unified survey of 58 foundation and
agentic models developed for single-cell research, spanning RNA, ATAC,
multi-omic, and spatial modalities. We categorize these methods into five
families-foundation, text-bridge, spatial, multimodal, epigenomic, and
agentic-and map them to eight key analytical tasks including annotation,
trajectory and perturbation modeling, and drug-response prediction. Drawing on
over 40 public datasets, we analyze benchmark suitability, data diversity, and
ethical or scalability constraints, and evaluate models across 10 domain
dimensions covering biological grounding, multi-omics alignment, fairness,
privacy, and explainability. By linking datasets, models, and evaluation
domains, LLM4Cell provides the first integrated view of language-driven
single-cell intelligence and outlines open challenges in interpretability,
standardization, and trustworthy model development.