Systematic comparison of sequencing-based spatial transcriptomic methods

作者：Yue You, Yuting Fu, Lanxiang Li, Zhongmin Zhang, Shikai Jia, Shihong Lu, Wenle Ren, Yifang Liu, Yang Xu, Xiaojing Liu, Xiaojing Liu, Fuqing Jiang, Guangdun Peng, Abhishek Sampath Kumar, Matthew E. Ritchie, Xiaodong Liu, Xiaodong Liu, Luyi Tian · 发表于：Nature Methods · 年份：2024 · DOI：10.1038/s41592-024-02325-3 · 被引用次数：192 · 研究领域：Single-cell and spatial transcriptomics、Immune cells in cancer、Gene expression and cancer classification

Recent developments of sequencing-based spatial transcriptomics (sST) have catalyzed important advancements by facilitating transcriptome-scale spatial gene expression measurement. Despite this progress, efforts to comprehensively benchmark different platforms are currently lacking. The extant variability across technologies and datasets poses challenges in formulating standardized evaluation metrics. In this study, we established a collection of reference tissues and regions characterized by well-defined histological architectures, and used them to generate data to compare 11 sST methods. We highlighted molecular diffusion as a variable parameter across different methods and tissues, significantly affecting the effective resolutions. Furthermore, we observed that spatial transcriptomic data demonstrate unique attributes beyond merely adding a spatial axis to single-cell data, including an enhanced ability to capture patterned rare cell states along with specific markers, albeit being influenced by multiple factors including sequencing depth and resolution. Our study assists biologists in sST platform selection, and helps foster a consensus on evaluation standards and establish a framework for future benchmarking efforts that can be used as a gold standard for the development and benchmarking of computational tools for spatial transcriptomic analysis.