arXiv:2607.23821cs.LGq-bio.GN2026-07

SCTA框架让单细胞基因发现更稳定可解释

SCTA: An Agentic Framework for Stable and Interpretable Target Gene Discovery from Single-Cell RNA Sequencing

论文配图:SCTA: An Agentic Framework for Stable and Interpretable Target Gene Discovery from Single-Cell RNA Sequencing
图 1 · 摘自论文原文
  • 将基因发现拆解为多个专业代理,按分析流程分步决策
  • 在胰腺炎数据上多次运行仍稳定选出关键靶点
  • 适合精准医学中需要可靠靶点的疾病研究者

从单细胞RNA测序(scRNA-seq)数据中识别治疗靶点仍是转化生物学中的核心挑战。与批量检测不同,scRNA-seq能捕捉异质性细胞状态和稀有亚群,但这种异质性也使靶点发现对分析流程中的预处理、细胞群体选择、差异表达分析及下游生物学解读等环节高度敏感。现有工作流和通用分析代理常产生不稳定或难以解释的靶点假设,限制了其在疾病导向发现中的可靠性。我们提出SCTA(Single-Cell Target Agent),一个以决策为中心的智能体框架,用于实现稳定且可解释的靶点发现。SCTA不将分析视为单一通用推理任务,而是将靶点发现分解为与单细胞分析流程中的关键决策点对应的专用代理,并通过结构化生物证据约束下游推理。在遗传性慢性胰腺炎的代表性消融研究中,我们证明SCTA的完整证据整合在独立运行中表现出最强的目标选择稳定性,同时恢复出与既往研究一致的生物学相关机制。结果表明,针对单细胞分析结构设计的决策感知代理协同策略,可提升靶点发现的鲁棒性、可解释性和临床实用性。

原文摘要 · Abstract (English)

Identifying therapeutic target genes from single-cell RNA sequencing (scRNA-seq) data remains a fundamental challenge in translational biology. Unlike bulk assays, scRNA-seq captures heterogeneous cellular states and rare subpopulations, but this same heterogeneity makes target discovery highly sensitive to analytical choices throughout the pipeline, including preprocessing, cell population selection, differential expression analysis, and downstream biological interpretation. As a result, existing workflows and general-purpose analysis agents often produce unstable or difficult-to-interpret target hypotheses, limiting their reliability for disease-focused discovery. We present SCTA (Single-Cell Target Agent), a decision-centric agentic framework for stable and interpretable target gene discovery from scRNA-seq data. Rather than treating analysis as a single general-purpose reasoning task, SCTA decomposes target discovery into specialized agents aligned with key decision points in the single-cell pipeline and constrains downstream reasoning with structured biological evidence. In a representative ablation study on hereditary chronic pancreatitis, we demonstrate that SCTA's full evidence integration yields the most stable target selection across independent runs among the tested configurations, while recovering biologically coherent, disease-relevant mechanisms validated in prior studies. These results suggest that decision-aware agent orchestration tailored to the structure of single-cell analysis can improve the robustness, interpretability, and practical utility of target discovery in precision medicine.

单细胞分析靶点发现智能体框架

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