构建跨模态跨尺度的虚拟细胞模型,提升生物数据决策可靠性
Artificial Intelligence Virtual Cells: From Measurements to Decisions across Modality, Scale, Dynamics, and Evaluation
- 提出细胞状态潜空间框架,通过测量、投影和干预实现多尺度耦合
- 验证显示跨实验室、平台的数据迁移能力有限,现有评估存在泄漏与覆盖偏差
- 强调功能空间读出与可复现评估,适合生物医学决策研究者使用
人工智能虚拟细胞(AIVCs)旨在从多模态、多尺度的细胞测量中学习可执行、与决策相关的细胞状态模型。尽管已有单细胞与空间基础模型、跨模态对齐改进、扰动图谱扩展及通路水平读出探索,但评估仍主要局限于单一数据集;实证表明,跨实验室与平台的迁移能力受限,部分数据划分存在泄漏与覆盖偏差,剂量、时间与组合效应尚未系统处理。跨尺度耦合也受制于分子、细胞与组织层面的锚点稀疏,且与科学或临床读出的对齐不一致。本文提出模型无关的细胞状态潜空间(CSL)视角,以算子语法组织学习:测量、升维/投影用于跨尺度耦合、干预用于剂量与调度。该视角推动跨模态、尺度、上下文与干预的决策对齐评估,强调通路活性、空间邻域及临床相关终点等函数空间读出。建议采用算子感知的数据设计、抗泄漏划分及透明校准与报告,以实现可复现的类比比较。
原文摘要 · Abstract (English)
Artificial Intelligence Virtual Cells (AIVCs) aim to learn executable, decision-relevant models of cell state from multimodal, multiscale measurements. Recent studies have introduced single-cell and spatial foundation models, improved cross-modality alignment, scaled perturbation atlases, and explored pathway-level readouts. Nevertheless, although held-out validation is standard practice, evaluations remain predominantly within single datasets and settings; evidence indicates that transport across laboratories and platforms is often limited, that some data splits are vulnerable to leakage and coverage bias, and that dose, time and combination effects are not yet systematically handled. Cross-scale coupling also remains constrained, as anchors linking molecular, cellular and tissue levels are sparse, and alignment to scientific or clinical readouts varies across studies. We propose a model-agnostic Cell-State Latent (CSL) perspective that organizes learning via an operator grammar: measurement, lift/project for cross-scale coupling, and intervention for dosing and scheduling. This view motivates a decision-aligned evaluation blueprint across modality, scale, context and intervention, and emphasizes function-space readouts such as pathway activity, spatial neighborhoods and clinically relevant endpoints. We recommend operator-aware data design, leakage-resistant partitions, and transparent calibration and reporting to enable reproducible, like-for-like comparisons.
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