arXiv:2605.28200cs.LGq-bio.GN2026-05KDD被引 1

不依赖固定网格,用几何先验重建单细胞空间结构。

Geometry-First Generative Spatial Single-Cell Reconstruction

论文配图:Geometry-First Generative Spatial Single-Cell Reconstruction
图 1 · 摘自论文原文
  • 基于空间转录组坐标学习细胞间几何关系,避免依赖固定网格。
  • 生成局部空间结构并融合多子集距离,实现全局坐标恢复。
  • 适合无配对数据场景,提升空间分布与邻域保真度。

单细胞RNA测序(scRNA-seq)可分析大量细胞但丢失空间信息,而空间转录组(ST)在低分辨率下保留部分空间结构。现有方法或解卷积斑点混合信号,或将细胞映射到固定斑点网格,受限于特定载玻片坐标系,尤其在无配对数据时表现不佳。本文提出GEARS,一种几何优先的框架,通过ST数据引导重建内在单细胞空间几何,无需细胞类型标签、组织图像或细胞-斑点对应关系。GEARS首先训练一个领域不变的表达编码器以对齐ST斑点与解离细胞,随后使用基于扩散的生成器结合EDM风格预处理,学习在姿态不变监督下的局部空间结构。推理时,对scRNA-seq细胞的多个重叠子集进行几何重建,聚合预测的成对距离,并求解全局距离几何问题,获得标准二维坐标和稠密距离矩阵。大量定量与定性实验表明,相比强基线模型,GEARS在跨切片泛化能力下持续提升全局距离保持性、局部邻域保真度及空间分布对齐效果。

原文摘要 · Abstract (English)

Single-cell RNA sequencing (scRNA-seq) profiles large numbers of cells but loses spatial context, whereas spatial transcriptomics (ST) preserves partial spatial structure at lower resolution. Most existing integration methods either deconvolve spot mixtures or map cells onto a measured spot lattice, which ties reconstructions to a fixed grid and slide-specific coordinate systems, a limitation that is especially problematic in unpaired settings. We propose GEARS, a geometry-first framework that reconstructs an intrinsic single-cell spatial geometry guided by ST, without relying on cell-type labels, histological images, or cell-to-spot assignment. GEARS first learns a domain-invariant expression encoder that aligns ST spots and dissociated cells, and then trains a permutation-equivariant generator with a diffusion-based refiner with EDM-style preconditioning to generate local spatial geometries under pose-invariant supervision derived from ST coordinates. At inference, GEARS reconstructs geometry on many overlapping subsets of scRNA-seq cells, aggregates predicted pairwise distances across subsets, and solves a global distance-geometry problem to obtain canonical two-dimensional coordinates and a dense distance matrix. Extensive quantitative and qualitative experiments, including cross-section generalization, show that GEARS consistently improves global distance preservation, local neighborhood fidelity, and spatial distribution alignment compared to strong spatial mapping and deconvolution baselines.

空间转录组单细胞几何重建扩散模型

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