ReCellTy: Domain-Specific Knowledge Graph Retrieval-Augmented LLMs Reasoning Workflow for Single-Cell Annotation
On the map: LLM reasoning → Clinical and biomedical applications
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Abstract (arXiv)
With the rapid development of large language models (LLMs), their application to cell type annotation has drawn increasing attention. However, general-purpose LLMs often face limitations in this specific task due to the lack of guidance from external domain knowledge. To enable more accurate and fully automated cell type annotation, we develop a globally connected knowledge graph comprising 18850 biological information nodes, including cell types, gene markers, features, and other related entities, along with 48,944 edges connecting these nodes, which is used by LLMs to retrieve entities associated with differential genes for cell reconstruction. Additionally, a multi-task reasoning workflow is designed to optimise the annotation process. Compared to general-purpose LLMs, our method improves human evaluation scores by up to 0.21 and semantic similarity by 6.1% across multiple tissue types, while more closely aligning with the cognitive logic of manual annotation. Meanwhile, it narrows the performance gap between large and small LLMs in cell type annotation, offering a paradigm for structured knowledge integration and reasoning in bioinformatics.
Key facts. No citing papers in the map yet (data through 14 Oct 2026). Placed in Clinical and biomedical applications, one of 17 directions in LLM reasoning. Builds on 12 of its 36 references that are in the map. First posted on arXiv 24 Apr 2025.
Builds on
12 of 36 references.
References · 12
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- 2024KG4Diagnosis: A Hierarchical Multi-Agent LLM Framework with Knowledge Graph Enhancement for Medical Diagnosiscited by 26
- 2024Learning the rules of peptide self-assembly through data mining with large language modelscited by 5
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- 2026SC-Arena: A Natural Language Benchmark for Single-Cell Reasoning with Knowledge-Augmented Evaluation
- 2024Single-Cell Omics Arena: A Benchmark Study for Large Language Models on Cell Type Annotation Using Single-Cell Data
- 2026SciHorizon-GENE: Benchmarking LLM for Life Sciences Inference from Gene Knowledge to Functional Understanding
- 2025LLM4Cell: A Survey of Large Language and Agentic Models for Single-Cell Biology
- 2025Towards Applying Large Language Models to Complement Single-Cell Foundation Models
- 2025Cell-o1: Training LLMs to Solve Single-Cell Reasoning Puzzles with Reinforcement Learning
- 2026GATHER: Convergence-Centric Hyper-Entity Retrieval for Zero-Shot Cell-Type Annotation
- 2026LLMBDC: Language Model for Biological Domains Oriented Clustering of Gene Ontology