Journal Article

Systematic comparison of sequencing-based spatial transcriptomic methods

Jiang, Fuqing, Lu, Shihong, Jia, Shikai, Ren, Wenle, Peng, Guangdun, Ritchie, Matthew E., You, Yue, Tian, Luyi, Liu, Yifang, Li, Lanxiang, Fu, Yuting, Xu, Yang, Liu, Xiaodong, Sampath Kumar, Abhishek, Zhang, Zhongmin, Liu, Xiaojing

2024

Overview

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. This analysis presents a systematic comparison of 11 sequencing-based spatial transcriptomics methods using well-characterized references, which offers insights into performance variations in spatial transcriptomic techniques.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/114/2416 / 631/61/514/1949 / Analysis / Animals / Benchmarks / Bioinformatics / Biological Microscopy / Biological Techniques / Biomedical and Life Sciences / Biomedical Engineering/Biotechnology / Computational Biology - methods / Efficiency / Gene expression / Gene Expression Profiling - methods / High-Throughput Nucleotide Sequencing - methods / Humans / Life Sciences / Methods / Mice / Molecular diffusion / Morphology / Performance evaluation / Proteomics / Sequence Analysis, RNA - methods / Single-Cell Analysis - methods / Software / Spatial analysis / Spatial data / Transcriptome / Transcriptomes / Transcriptomics