PACE通过几何感知的运输模型,从破坏性单细胞快照中重建更准确的发育轨迹。
PACE: Geometry-Aware Bridge Transport for Single-Cell Trajectory Inference

- 基于局部几何结构设计动态度量,避免异步发育导致的轨迹错配
- 在7个数据集上平均降低23.7%的分布距离,显著提升轨迹重建精度
- 无需细胞配对或速度监督,适合生物发育研究与复杂轨迹推断
从破坏性的时序单细胞快照中推断细胞轨迹本质上是病态问题:既无法观测跨时间的细胞对应关系,也无法直接获取连续轨迹,仅凭快照分布无法唯一确定潜在动态。现有最优传输与基于流的方法通常依赖观测时间点上的欧氏邻近性进行细胞耦合,当发育不同步时易造成轨迹错配,同一实验时间点的细胞可能处于不同的潜伏伪时间阶段。本文提出PACE框架,通过三个耦合组件从破坏性时序快照中恢复几何一致的连续运输动态:首先构建状态和时间依赖的各向异性黎曼度量,沿局部支持的切向方向赋予低运输代价,同时惩罚法向速度分量;其次交替优化路径作用成本下的跨时间耦合,并拟合保持端点的神经桥接模型;最后将学习到的桥接动态提炼为全局连续时间的速度场。在七个受控及生物数据集的九项独立重建实验中,PACE整体表现最优,平均使MMD、Wasserstein-1距离和Wasserstein-2距离下降23.7%。在类胚体分化基准上,其RNA速度对齐性能提升15.4%,且训练过程中无需显式细胞配对、谱系追踪或RNA速度监督。代码已开源于https://github.com/AI4Science-WestlakeU/PACE。
原文摘要 · Abstract (English)
Single-cell trajectory inference from destructive time-course snapshots is fundamentally ill-posed: neither cross-time cell correspondences nor continuous trajectories are observed, so the snapshot distributions alone do not uniquely determine the underlying dynamics. Existing optimal transport and flow-based methods typically couple cells by Euclidean proximity at observed clock times, which can misalign trajectories when development is asynchronous and cells sampled at the same experimental time occupy different latent pseudotime stages. We propose PACE, a trajectory inference framework that recovers geometry-consistent continuous transport dynamics from destructive time-course snapshots through three coupled components. First, PACE constructs a state- and time-dependent anisotropic Riemannian metric that assigns low transport cost along locally supported tangent directions while penalizing normal velocity components. Second, it alternates between refining cross-time couplings under the induced path-action cost and fitting endpoint-preserving neural bridges between adjacent snapshots. Third, it distills the learned bridge dynamics into a global continuous-time velocity field over cellular states. Across seven controlled and biological datasets covering nine held-out reconstruction experiments, PACE achieves the strongest overall reconstruction performance, reducing MMD, Wasserstein-1 distance, and Wasserstein-2 distance by 23.7% on average relative to the strongest competing baseline. PACE also improves RNA-velocity alignment by 15.4% on an embryoid body differentiation benchmark, without requiring explicit cell pairing, lineage tracing, or RNA-velocity supervision during training. Code is available at https://github.com/AI4Science-WestlakeU/PACE.
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