让虚拟细胞模型自动修正错误,从假设到代码闭环优化。
CellScientist: Dual-Space Hierarchical Orchestration for Closed-Loop Refinement of Virtual Cell Models

- 构建高阶假设与低阶代码的双空间框架,实现跨层级反馈。
- 在形态与转录组基准上优于基线模型,支持可审计的迭代修正。
- 适合需要精准迭代优化生物模型的研究者使用。
虚拟细胞建模(VCM)不仅需预测扰动响应,还需在预测失败时支持定向修正。现有大语言模型辅助建模流程面临修正路径模糊问题:预测偏差通过可执行实现发现,但修正可能涉及建模假设、表征设计、实现方式或任务约束。缺乏跨层级的结构化反馈传播,导致迭代修正可能仅修复代码,却忽略根本假设缺陷。我们提出CellScientist,一种双空间分层框架,将建模决策表示为结构化状态,在任务与接口约束下生成合法程序,并将执行偏差回传至目标假设或实现更新。该机制实现从假设→实现→假设的闭环,使失败成为模型精炼的结构化信号而非调试事件。在形态学与转录组基准测试中,结合单细胞扰动评估,经CellScientist选择的最终可执行模型在固定划分与评估协议下优于参考基线,且工作流生成可审计的修正轨迹。
原文摘要 · Abstract (English)
Virtual Cell Modeling (VCM) requires models that not only predict perturbation responses, but also support targeted revision when predictions fail. Current LLM-assisted modeling workflows face a refinement-routing problem: prediction discrepancies are observed through executable implementations, but the relevant revision may involve the modeling assumption, representation design, implementation, or task constraint. Without structured feedback propagation across these levels, iterative refinement may repair code while failing to revise the assumption responsible for the discrepancy. We propose CellScientist, a dual-space hierarchical framework that couples a high-level hypothesis space with a low-level executable implementation space. CellScientist represents modeling decisions as structured states, realizes them as admissible programs under task and interface constraints, and routes execution discrepancies back to targeted hypothesis or implementation updates. This enables a closed Hypothesis -> Implementation -> Hypothesis loop where failures become structured signals for model refinement rather than debugging events. Across morphology and transcriptomic benchmarks, with additional single-cell perturbation evaluations, the final executable models selected by CellScientist improve over reference baselines under fixed split and evaluation protocols, while the workflow produces auditable refinement traces.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。