用多智能体推理框架提升单细胞注释准确率,解决难判别基因和新状态标注难题。
MAT-Cell: A Multi-Agent Tree-Structured Reasoning Framework for Batch-Level Single-Cell Annotation

- 分两阶段:先构建候选特异性前提,再通过多轮辩论生成可追溯的推理树
- 在五个数据集上平均准确率达75.5%,显著优于基线模型(64.2%)
- 适合需要高可解释性、低部署成本的单细胞数据分析人员
当最丰富基因不具区分性或目标状态未被固定参考图谱覆盖时,自动化单细胞注释面临挑战。MAT-Cell是一种提示驱动的批处理单细胞注释框架,将证据定位与标签决策分离。首先通过逆向验证查询(RVQ)整合组织上下文、差异表达基因及大语言模型生成的生物先验,形成候选特异性前提;验证者智能体将这些前提转化为显式的前提-主张推理树,并通过有限轮次的多智能体辩论对主张进行比较、质疑与修正,最终达成共识或裁定。返回的三段论推导树(SDT)提供可审计的辩论轨迹,而非形式化证明。在五个数据集的开放候选基准测试中,本地部署的Qwen3-30B模型配合MAT-Cell实现75.5%平均准确率,优于最强的链式思维基线(64.2%)和scPilot变体(51.9%)。在三个物种的真值候选基准中,MAT-Cell在不同模型骨架下保持竞争力,本地推理大幅降低批量注释的经济成本。代码已公开于https://anonymous.4open.science/r/MATCell-4067。
原文摘要 · Abstract (English)
Automated single-cell annotation is difficult when the most abundant genes are not the most discriminative ones, or when a target state is poorly covered by a fixed reference atlas. GPTCelltype-style one-shot prompting allows large language models (LLMs) to produce plausible labels from generic expression signals, while reference-based annotators can force unfamiliar states into the nearest known category. We propose MAT-Cell, a prompt-driven framework for batch-level single-cell annotation that separates evidence grounding from label decision. MAT-Cell first uses Reverse Verification Query (RVQ) to combine tissue context, observed differentially expressed genes, and LLM-elicited biological priors into structured candidate-specific premises. Verifier agents then convert these premises into explicit premise-to-claim reasoning trees, and bounded multi-round debate compares,challenges, and revises the resulting claims before consensus or final adjudication.The returned Syllogistic Derivation Tree (SDT) provides an auditable debate trace rather than a formal proof of the annotation. In open-candidate benchmarks across five datasets, a locally deployed Qwen3-30B model with MAT-Cell achieves 75.5% average accuracy, compared with 64.2% for the strongest evaluated CoT baseline and 51.9% for the strongest evaluated scPilot variant. In oracle-candidate bench-marks across three species,MAT-Cell remains competitive across backbones, and local inference substantially reduces monetary cost for batch annotation. Code is available at: https://anonymous.4open.science/r/MATCell-4067
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