Spotiphy enables single-cell spatial whole transcriptomics across an entire section.

IF 36.1 1区生物学 Q1 BIOCHEMICAL RESEARCH METHODS

Nature Methods Pub Date : 2025-03-12 DOI:10.1038/s41592-025-02622-5

Jiyuan Yang, Ziqian Zheng, Yun Jiao, Kaiwen Yu, Sheetal Bhatara, Xu Yang, Sivaraman Natarajan, Jiahui Zhang, Qingfei Pan, John Easton, Koon-Kiu Yan, Junmin Peng, Kaibo Liu, Jiyang Yu

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引用次数: 0

Abstract

Spatial transcriptomics (ST) has advanced our understanding of tissue regionalization by enabling the visualization of gene expression within whole-tissue sections, but current approaches remain plagued by the challenge of achieving single-cell resolution without sacrificing whole-genome coverage. Here we present Spotiphy (spot imager with pseudo-single-cell-resolution histology), a computational toolkit that transforms sequencing-based ST data into single-cell-resolved whole-transcriptome images. Spotiphy delivers the most precise cellular proportions in extensive benchmarking evaluations. Spotiphy-derived inferred single-cell profiles reveal astrocyte and disease-associated microglia regional specifications in Alzheimer's disease and healthy mouse brains. Spotiphy identifies multiple spatial domains and alterations in tumor-tumor microenvironment interactions in human breast ST data. Spotiphy bridges the information gap and enables visualization of cell localization and transcriptomic profiles throughout entire sections, offering highly informative outputs and an innovative spatial analysis pipeline for exploring complex biological systems.

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来源期刊

Nature Methods 生物-生化研究方法

CiteScore

58.70

自引率

1.70%

发文量

326

审稿时长

1 months

期刊介绍： Nature Methods is a monthly journal that focuses on publishing innovative methods and substantial enhancements to fundamental life sciences research techniques. Geared towards a diverse, interdisciplinary readership of researchers in academia and industry engaged in laboratory work, the journal offers new tools for research and emphasizes the immediate practical significance of the featured work. It publishes primary research papers and reviews recent technical and methodological advancements, with a particular interest in primary methods papers relevant to the biological and biomedical sciences. This includes methods rooted in chemistry with practical applications for studying biological problems.