Sottosanti Andrea, Risso Davide
University of Padova.
Ann Appl Stat. 2023 Jun;17(2):1444-1468. doi: 10.1214/22-aoas1677. Epub 2023 May 1.
Spatial transcriptomics is a groundbreaking technology that allows the measurement of the activity of thousands of genes in a tissue sample and maps where the activity occurs. This technology has enabled the study of the spatial variation of the genes across the tissue. Comprehending gene functions and interactions in different areas of the tissue is of great scientific interest, as it might lead to a deeper understanding of several key biological mechanisms, such as cell-cell communication or tumor-microenvironment interaction. To do so, one can group cells of the same type and genes that exhibit similar expression patterns. However, adequate statistical tools that exploit the previously unavailable spatial information to more coherently group cells and genes are still lacking. In this work, we introduce SpaRTaCo, a new statistical model that clusters the spatial expression profiles of the genes according to a partition of the tissue. This is accomplished by performing a co-clustering, i.e., inferring the latent block structure of the data and inducing two types of clustering: of the genes, using their expression across the tissue, and of the image areas, using the gene expression in the where the RNA is collected. Our proposed methodology is validated with a series of simulation experiments and its usefulness in responding to specific biological questions is illustrated with an application to a human brain tissue sample processed with the 10X-Visium protocol.
空间转录组学是一项开创性技术,它能够测量组织样本中数千个基因的活性,并绘制出活性发生的位置。这项技术使得对整个组织中基因的空间变异进行研究成为可能。了解组织不同区域的基因功能和相互作用具有重大的科学意义,因为这可能会加深对一些关键生物学机制的理解,比如细胞间通讯或肿瘤微环境相互作用。为此,可以将相同类型的细胞以及表现出相似表达模式的基因归为一组。然而,目前仍然缺乏能够利用此前无法获取的空间信息来更连贯地对细胞和基因进行分组的适当统计工具。在这项工作中,我们引入了SpaRTaCo,这是一种新的统计模型,它根据组织的划分对基因的空间表达谱进行聚类。这是通过执行共聚类来实现的,即推断数据的潜在块结构,并诱导两种类型的聚类:一种是根据基因在整个组织中的表达对基因进行聚类,另一种是根据在收集RNA的位置的基因表达对图像区域进行聚类。我们提出的方法通过一系列模拟实验得到了验证,并通过应用于用10X-Visium协议处理的人类脑组织样本,说明了其在回答特定生物学问题方面的实用性。