Department of Computer Science, Princeton University, 35 Olden St, Princeton, NJ 08540, USA.
Department of Computer Science, Princeton University, 35 Olden St, Princeton, NJ 08540, USA.
Cell Syst. 2022 Oct 19;13(10):786-797.e13. doi: 10.1016/j.cels.2022.09.002.
Spatially resolved transcriptomics (SRT) technologies measure gene expression at known locations in a tissue slice, enabling the identification of spatially varying genes or cell types. Current approaches for these tasks assume either that gene expression varies continuously across a tissue or that a tissue contains a small number of regions with distinct cellular composition. We propose a model for SRT data from layered tissues that includes both continuous and discrete spatial variation in expression and an algorithm, Belayer, to learn the parameters of this model. Belayer models gene expression as a piecewise linear function of the relative depth of a tissue layer with possible discontinuities at layer boundaries. We use conformal maps to model relative depth and derive a dynamic programming algorithm to infer layer boundaries and gene expression functions. Belayer accurately identifies tissue layers and biologically meaningful spatially varying genes in SRT data from the brain and skin.
空间分辨转录组学(SRT)技术可在组织切片的已知位置测量基因表达,从而能够识别空间变化的基因或细胞类型。目前用于这些任务的方法要么假设基因表达在整个组织中连续变化,要么假设组织中只有少数具有不同细胞组成的区域。我们提出了一种用于分层组织的 SRT 数据的模型,该模型包括表达的连续和离散空间变化,以及一种算法 Belayer,用于学习该模型的参数。Belayer 将基因表达建模为组织层相对深度的分段线性函数,在层边界处可能存在不连续。我们使用共形映射来建模相对深度,并推导出一种动态规划算法来推断层边界和基因表达函数。Belayer 可以准确识别大脑和皮肤 SRT 数据中的组织层和具有生物学意义的空间变化基因。