用几何约束建模细胞动态转变,让生成结果更符合真实生物学过程。
FreeBridge: Variational Schrödinger Bridges for Cellular Transition Dynamics

- 基于单细胞分割表示构建固定细胞流形,约束随机传输路径
- 在多个数据集上保持终点对齐,且中间过渡更少违反形态支持
- 适合关注药物作用机制与细胞轨迹可解释性的生物研究者
高内涵成像实验可量化细胞对化学和基因扰动的响应,但因细胞在采集时被化学固定,个体细胞的连续轨迹无法观测。扰动建模因此转化为仅从控制组与处理组的独立分布中推断随机传输过程。尽管近期生成模型在终点对齐上表现良好,但边界一致性并不能决定中间演化:多个随机过程可能连接相同的边际分布,却经过未被观测单细胞形态支持的区域。我们提出 extbf{FreeBridge},一种基于端点仅监督的单细胞转变建模的薛定谔桥方法。FreeBridge 将原子状态定义为实例分割的单细胞表征,建立固定的细胞流形,并通过经验潜在空间支持正则化,约束学习到的随机传输在此几何结构内进行。在 BBBC021、RxRx1 与 JUMP 数据集上,FreeBridge 在统一评估协议下维持或提升终点保真度与作用机制保留能力;在 BBBC021 上进一步减少了中间支持违规现象。这些结果凸显了几何约束对生物学可解释性扰动动态的重要性。
原文摘要 · Abstract (English)
High-content imaging assays quantify cellular responses to chemical and genetic perturbations, yet continuous trajectories of individual cells are unobservable because cells are chemically fixed at acquisition. Perturbation modeling therefore reduces to inferring stochastic transport between control and treated populations observed only as separate marginals. While recent generative models achieve strong end-point alignment, boundary consistency does not determine intermediate evolution: multiple stochastic processes may connect identical marginals while traversing regions unsupported by observed single-cell morphologies. We introduce \textbf{FreeBridge}, a Schrödinger Bridge formulation for single-cell transition modeling under endpoint-only supervision. FreeBridge defines atomic states as instance-segmented single-cell representations, establishing a fixed cellular manifold, and learns stochastic transport constrained within this geometry via empirical latent support regularization. Across BBBC021, RxRx1, and JUMP, FreeBridge maintains competitive or improved endpoint fidelity and mechanism-of-action retention under a unified evaluation protocol; on BBBC021, it further reduces intermediate support violations. These findings highlight the importance of geometric grounding for biologically interpretable perturbation dynamics. Project page: https://y-research-sbu.github.io/FreeBridge/.
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