针对基因组合注释难题,提出全局收敛点检索方法,显著降低大模型调用次数。
GATHER: Convergence-Centric Hyper-Entity Retrieval for Zero-Shot Cell-Type Annotation

- 通过全局多源图遍历定位多个基因共同可达的收敛节点,捕捉基因协同效应。
- 在免疫和肺部数据集上准确率分别达27.45%和59.64%,仅需单次大模型调用。
- 适合生物信息学中零样本细胞类型注释场景,尤其对高维基因查询高效实用。
零样本单细胞类型注释旨在不依赖训练数据的情况下,仅根据表达基因确定细胞类型。现有基于知识图谱的RAG方法通过从源实体扩展并依赖迭代大模型推理来检索证据,但在每条查询包含数十至数百个基因的场景下,单一基因无决定性作用,标签仅由基因共现产生。传统基于个体基因的局部探索策略难以应对这种超实体查询,导致可扩展性差且大模型调用成本高。本文提出GATHER(Graph-Aware Traversal with Hyper-Entity Retrieval),一种面向超实体查询的收敛中心检索器。它进行全局多源图遍历,识别出被多个输入基因共同可达的拓扑收敛点——即高信息量的超实体,能捕捉基因间的协同关系。结合节点与路径重要性评分,GATHER在检索阶段完全无需大模型参与。在自构建的细胞中心生物知识图谱(VCKG)上,GATHER在两大数据集(Immune、Lung)上超越强基线方法(ToG、ToG-2、RoG、PoG),实现最高精确匹配准确率(27.45% 和 59.64%),且每样本仅需一次大模型调用,远低于基线的2–61次。结果表明,收敛节点能将多实体信号压缩为紧凑高信息量证据,其单位信息量优于多跳路径,提供了一种高效的全局替代方案。
原文摘要 · Abstract (English)
Zero-shot single-cell cell-type annotation aims to determine a cell's type from a given set of expressed genes without any training. Existing knowledge-graph-based RAG approaches retrieve evidence by expanding from source entities and relying on iterative LLM reasoning. However, in this setting each query contains tens to hundreds of genes, where no single gene is decisive and the label emerges only from their collective co-occurrence. Such hyper-entity queries fundamentally challenge local, entity-wise exploration strategies, which reason from individual genes, leading to poor scalability and substantial LLM cost. We propose GATHER (Graph-Aware Traversal with Hyper-Entity Retrieval), a convergence-centric retriever tailored to hyper-entity queries. It performs global multi-source graph traversal and identifies topological convergence points -- nodes jointly reachable from many input genes. These convergence nodes act as high-information hyper-entities that capture entity synergy. By incorporating node- and path-importance scoring, GATHER selects informative evidence entirely without LLM involvement during retrieval. Instantiated on a self-constructed cell-centric biological knowledge graph (VCKG), GATHER outperforms strong KG-RAG baselines (ToG, ToG-2, RoG, PoG) on two datasets (Immune and Lung), achieving the highest exact-match accuracy (27.45% and 59.64%) with only a single LLM call per sample, compared to 2--61 calls for KG-RAG baselines. Our results demonstrate that convergence nodes compress multi-entity signals into compact, high-information evidence that conveys more per item than multi-hop paths, providing an efficient global alternative to local entity-wise reasoning.
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