arXiv:2608.15306stat.MLcs.LG2026-08

用几何方法分析基因表达网络的时空演化,可重建发育轨迹并量化变化。

A Unified Geometric Framework for Developmental Analysis of Spatial Transcriptomic Data

论文配图:A Unified Geometric Framework for Developmental Analysis of Spatial Transcriptomic Data
图 1 · 摘自论文原文
  • 将每个发育阶段建模为结合表达与空间关系的图,嵌入格罗莫夫-沃瑟斯坦空间。
  • 通过测地线插值实现发育阶段连续过渡,曲率变化与实测数据高度一致。
  • 适合研究发育、组织动态等生物网络演化问题,尤其关注结构变化。

高通量单细胞与空间转录组技术提供高分辨率的细胞状态快照,但其破坏性导致无法对同一细胞进行重复测量。因此,时间与空间动态需从独立采样且未对齐的细胞群体中推断,难以重建发育轨迹。最优传输(OT)提供了对齐细胞群体和推断发育轨迹的几何框架,但现有方法多聚焦于基因表达空间中细胞分布的演化,而非基因表达网络所编码的关系结构。为此,我们提出一种基于格罗莫夫-沃瑟斯坦(GW)空间嵌入的统一几何框架,用于分析基因表达网络的时空演化。通过将每个发育阶段表示为结合基因表达与空间邻近性的图,该方法实现了跨时间的网络结构比较、通过GW测地线的发育阶段连续插值,以及利用奥利维耶-里奇曲率量化网络层面的变化。我们在果蝇时空转录组数据集上验证了该框架,结果显示GW测地线插值再现了真实基因表达网络中观察到的曲率动态主要趋势。与联合表征时空信息的高阶共最优传输(COOT)距离的一致性进一步验证了该框架的有效性,表明超网络表示能有效记录随时间变化的关键生物学特征。总体而言,本方法为研究动态演化的生物网络提供了一个统一的几何视角。

原文摘要 · Abstract (English)

High-throughput single-cell and spatial transcriptomic technologies provide high-resolution snapshots of heterogeneous cellular states, but their destructive nature prevents repeated measurements of the same cells over time. Consequently, temporal and spatial dynamics must be inferred from independently sampled, unaligned cell populations, making it challenging to reconstruct developmental trajectories. Optimal transport (OT) offers a geometric framework for aligning cell populations and inferring developmental trajectories, but many existing approaches focus on modeling the evolution of distributions of cells in gene expression space rather than the relational structure encoded by gene expression networks. To address this limitation, we introduce a geometric framework for analyzing the spatiotemporal evolution of gene expression networks through embeddings in Gromov--Wasserstein (GW) space. By representing each developmental stage as a graph combining gene expression and spatial proximity, our approach enables comparisons of network structure across time, continuous interpolation between developmental stages via GW geodesics, and quantification of network-level changes using Ollivier-Ricci curvature. We evaluate our framework on a spatiotemporal transcriptomic \textit{Drosophila} dataset and show that GW geodesic interpolations reproduce main trends in curvature dynamics observed in empirical gene expression networks. Agreement with higher-order Co-Optimal Transport (COOT) distances, which jointly represent spatial and temporal information, further validates the framework and suggests that hypernetwork representations successfully record salient biological changes across time. In general, our approach provides a unified geometric approach to study dynamically evolving biological networks.

空间转录组发育生物学网络演化几何学习

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