Partial alignment of multislice spatially resolved transcriptomics data.
Partial alignment of multislice spatially resolved transcriptomics data.
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DOI：
10.1101/gr.277670.123
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发表时间：
2023-07
期刊：
影响因子：
7
通讯作者：
Raphael, Benjamin J
中科院分区：
文献类型：
--
作者：
Liu, Xinhao;Zeira, Ron;Raphael, Benjamin J
空间分辨转录组学（SRT）技术测量组织切片中数千个位置处的信使RNA（mRNA）表达。然而，几乎所有的SRT技术都测量从3D组织提取的二维（2D）切片中的表达，从而丢失了在来自相同组织的多个切片之间共享的信息。跨多个切片整合SRT数据可以帮助恢复这些信息并改善下游表达分析，但多切片比对和整合仍然是一项具有挑战性的任务。用于整合SRT数据的现有方法要么不使用空间信息，要么假设组织的形态在很大程度上跨切片保留，这是由于生物或技术原因而经常违反的假设。我们介绍PASTE 2，一种用于多层SRT数据集的部分对齐和3D重建的方法，仅允许对齐切片和/或切片特定细胞类型之间的部分重叠。PASTE 2制定了一个新的部分融合Gromov-Wasserstein最优运输问题，我们使用条件梯度算法解决。PASTE 2包括一个模型选择程序，用于估计切片之间的重叠部分，并可选地使用来自伴随一些SRT实验的组织学图像的信息。我们在模拟和真实的数据上表明，PASTE 2比现有方法获得更准确的比对。我们进一步使用PASTE 2从16切片Stereo-seq数据集重建果蝇胚胎中基因表达的3D图谱。PASTE 2可以对来自多种SRT技术的多切片数据集进行精确比对，从而能够在广泛的生物学应用中对空间基因表达进行详细研究。
Spatially resolved transcriptomics (SRT) technologies measure messenger RNA (mRNA) expression at thousands of locations in a tissue slice. However, nearly all SRT technologies measure expression in two-dimensional (2D) slices extracted from a 3D tissue, thus losing information that is shared across multiple slices from the same tissue. Integrating SRT data across multiple slices can help recover this information and improve downstream expression analyses, but multislice alignment and integration remains a challenging task. Existing methods for integrating SRT data either do not use spatial information or assume that the morphology of the tissue is largely preserved across slices, an assumption that is often violated because of biological or technical reasons. We introduce PASTE2, a method for partial alignment and 3D reconstruction of multislice SRT data sets, allowing only partial overlap between aligned slices and/or slice-specific cell types. PASTE2 formulates a novel partial fused Gromov-Wasserstein optimal transport problem, which we solve using a conditional gradient algorithm. PASTE2 includes a model selection procedure to estimate the fraction of overlap between slices, and optionally uses information from histological images that accompany some SRT experiments. We show on both simulated and real data that PASTE2 obtains more accurate alignments than existing methods. We further use PASTE2 to reconstruct a 3D map of gene expression in a Drosophila embryo from a 16 slice Stereo-seq data set. PASTE2 produces accurate alignments of multislice data sets from multiple SRT technologies, enabling detailed studies of spatial gene expression across a wide range of biological applications.