arXiv:2605.00545cs.LGcs.AI2026-05

无需模拟即可重建单细胞分裂死亡动态,更真实还原细胞命运分支。

Beyond Continuity: Simulation-free Reconstruction of Discrete Branching Dynamics from Single-cell Snapshots

论文配图:Beyond Continuity: Simulation-free Reconstruction of Discrete Branching Dynamics from Single-cell Snapshots
图 1 · 摘自论文原文
  • 基于非平衡薛定谔桥,直接建模细胞的随机与离散增殖死亡过程
  • 在真实和模拟数据上优于或媲美确定性方法,且能生成真实分裂死亡轨迹
  • 适合研究发育、肿瘤等涉及细胞命运决策的单细胞动态场景

从破坏性单细胞快照推断细胞轨迹面临随机性和非守恒质量动态(如增殖与凋亡)的挑战。现有非平衡最优传输方法将质量视为连续流体,在群体层面进行推断,但难以捕捉单细胞分辨率下出生-死亡事件的离散跳跃特性,而这一特性对理解谱系分支与命运决定至关重要。本文提出无模拟的非平衡薛定谔桥(USB),一种学习底层动态的框架,有效整合随机性与非平衡效应,并在单细胞层面建模离散跳跃式的出生-死亡过程。理论上,USB为分支薛定谔桥(BSB)问题提供可计算解,赋予微观解释:每个细胞同时经历布朗运动与离散出生-死亡跳跃。技术上,通过引入无模拟训练目标,实现高效求解,可扩展至高维组学数据。实验表明,USB在模拟与真实数据集上均达到优于或媲美确定性基线的轨迹重建性能,并首次实现单细胞分辨率下的真实出生-死亡动态模拟。

原文摘要 · Abstract (English)

Inferring cellular trajectories from destructive snapshots is complicated by the challenges of stochasticity and non-conservative mass dynamics such as cell proliferation and apoptosis. Existing unbalanced Optimal Transport (OT) methods treat mass as a continuous fluid, performing inference at the population level. However, this macroscopic view often fails to capture the discrete, jump-like nature of birth-death events at single-cell resolution, which is essential for understanding lineage branching and fate decisions. We present Unbalanced Schrödinger Bridge (USB), a simulation-free framework for learning underlying dynamics that effectively integrates both stochastic and unbalanced effects which also models the discrete, jump-like birth-death dynamics at single-cell resolution. Theoretically, USB provides a tractable solution to the Branching Schrödinger Bridge (BSB) problem, offering a rigorous microscopic interpretation where individual cells undergo both Brownian motion and discrete birth-death jumps. Technically, the method implements an efficient solver by introducing a simulation-free training objective that effectively scales to high-dimensional omics data. Empirically, we demonstrate on both simulated and real-world datasets that USB not only achieves trajectory reconstruction performance better than or comparable to deterministic baselines but also uniquely enables realistic discrete simulation of birth-death dynamics at single-cell resolution.

单细胞轨迹薛定谔桥细胞命运动态建模

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