2024年11月18日，《自然—方法学》杂志在线发表了德国科学家的一项最新研究成果。来自慕尼黑工业大学的Fabian J. Theis课题组开发出靶向空间转录组学的探针集选择。

研究人员表示，靶向空间转录组学方法通过测量一组预定义基因的表达，在单细胞和亚细胞分辨率下捕捉组织中细胞类型和状态的拓扑结构。选择最佳的探针基因集对于捕捉组织中存在的空间信号至关重要。

这需要选择最具信息性且最简洁的基因集进行分析（基因集选择），并为其设计探针（探针设计）。然而，当前的选择往往依赖于标记基因，限制了它们检测连续空间信号或新状态的能力。

研究人员提出了Spapros，一个端到端的探针集选择管道。它优化了基因集特异性（用于细胞类型识别）和细胞内类型表达变异，以解决空间上不同的细胞群体，同时考虑先验知识、探针设计和表达限制。研究人员评估了Spapros，并显示它在细胞类型恢复和恢复细胞类型外的表达变异方面优于其他选择方法。

此外，研究人员使用Spapros设计了一个成人肺组织的单细胞分辨率原位杂交（SCRINSHOT）实验，展示了使用Spapros选择的探针如何识别感兴趣的细胞类型并检测到细胞类型内部的空间变异。

附：英文原文

Title: Probe set selection for targeted spatial transcriptomics

Author: Kuemmerle, Louis B., Luecken, Malte D., Firsova, Alexandra B., Barros de Andrade e Sousa, Lisa, Straer, Lena, Mekki, Ilhem Isra, Campi, Francesco, Heumos, Lukas, Shulman, Maiia, Beliaeva, Valentina, Hediyeh-Zadeh, Soroor, Schaar, Anna C., Mahbubani, Krishnaa T., Sountoulidis, Alexandros, Balassa, Tams, Kovacs, Ferenc, Horvath, Peter, Piraud, Marie, Ertrk, Ali, Samakovlis, Christos, Theis, Fabian J.

Issue&Volume: 2024-11-18

Abstract: Targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. This requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design). However, current selections often rely on marker genes, precluding them from detecting continuous spatial signals or new states. We present Spapros, an end-to-end probe set selection pipeline that optimizes both gene set specificity for cell type identification and within-cell type expression variation to resolve spatially distinct populations while considering prior knowledge as well as probe design and expression constraints. We evaluated Spapros and show that it outperforms other selection approaches in both cell type recovery and recovering expression variation beyond cell types. Furthermore, we used Spapros to design a single-cell resolution in situ hybridization on tissues (SCRINSHOT) experiment of adult lung tissue to demonstrate how probes selected with Spapros identify cell types of interest and detect spatial variation even within cell types.

DOI: 10.1038/s41592-024-02496-z

Source: https://www.nature.com/articles/s41592-024-02496-z