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空间分辨转录组数据中细胞依赖性和基因关联的联合贝叶斯估计

Joint Bayesian estimation of cell dependence and gene associations in spatially resolved transcriptomic data.

作者信息

Chakrabarti Arhit, Ni Yang, Mallick Bani K

机构信息

Department of Statistics, Texas A &M University, College Station, TX, 77843, USA.

出版信息

Sci Rep. 2024 Apr 25;14(1):9516. doi: 10.1038/s41598-024-60002-z.

Abstract

Recent technologies such as spatial transcriptomics, enable the measurement of gene expressions at the single-cell level along with the spatial locations of these cells in the tissue. Spatial clustering of the cells provides valuable insights into the understanding of the functional organization of the tissue. However, most such clustering methods involve some dimension reduction that leads to a loss of the inherent dependency structure among genes at any spatial location in the tissue. This destroys valuable insights of gene co-expression patterns apart from possibly impacting spatial clustering performance. In spatial transcriptomics, the matrix-variate gene expression data, along with spatial coordinates of the single cells, provides information on both gene expression dependencies and cell spatial dependencies through its row and column covariances. In this work, we propose a joint Bayesian approach to simultaneously estimate these gene and spatial cell correlations. These estimates provide data summaries for downstream analyses. We illustrate our method with simulations and analysis of several real spatial transcriptomic datasets. Our work elucidates gene co-expression networks as well as clear spatial clustering patterns of the cells. Furthermore, our analysis reveals that downstream spatial-differential analysis may aid in the discovery of unknown cell types from known marker genes.

摘要

诸如空间转录组学等最新技术能够在单细胞水平上测量基因表达,同时还能确定这些细胞在组织中的空间位置。细胞的空间聚类为理解组织的功能组织提供了有价值的见解。然而,大多数此类聚类方法都涉及某种降维操作,这会导致组织中任何空间位置的基因之间固有的依赖结构丢失。这不仅可能影响空间聚类性能,还会破坏基因共表达模式的宝贵见解。在空间转录组学中,矩阵变量基因表达数据以及单细胞的空间坐标,通过其行和列协方差提供了有关基因表达依赖性和细胞空间依赖性的信息。在这项工作中,我们提出了一种联合贝叶斯方法,用于同时估计这些基因和空间细胞相关性。这些估计为下游分析提供了数据总结。我们通过对几个真实空间转录组数据集的模拟和分析来说明我们的方法。我们的工作阐明了基因共表达网络以及细胞清晰的空间聚类模式。此外,我们的分析表明,下游空间差异分析可能有助于从已知标记基因中发现未知细胞类型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4715/11045727/624cd58bd1c0/41598_2024_60002_Fig1_HTML.jpg

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