Nature Communications (Apr 2025)

Stereopy: modeling comparative and spatiotemporal cellular heterogeneity via multi-sample spatial transcriptomics

  • Shuangsang Fang,
  • Mengyang Xu,
  • Lei Cao,
  • Xiaobin Liu,
  • Marija Bezulj,
  • Liwei Tan,
  • Zhiyuan Yuan,
  • Yao Li,
  • Tianyi Xia,
  • Longyu Guo,
  • Vladimir Kovacevic,
  • Junhou Hui,
  • Lidong Guo,
  • Chao Liu,
  • Mengnan Cheng,
  • Li’ang Lin,
  • Zhenbin Wen,
  • Bojana Josic,
  • Nikola Milicevic,
  • Ping Qiu,
  • Qin Lu,
  • Yumei Li,
  • Leying Wang,
  • Luni Hu,
  • Chao Zhang,
  • Qiang Kang,
  • Fengzhen Chen,
  • Ziqing Deng,
  • Junhua Li,
  • Mei Li,
  • Shengkang Li,
  • Yi Zhao,
  • Guangyi Fan,
  • Yong Zhang,
  • Ao Chen,
  • Yuxiang Li,
  • Xun Xu

DOI
https://doi.org/10.1038/s41467-025-58079-9
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 19

Abstract

Read online

Abstract Understanding complex biological systems requires tracing cellular dynamic changes across conditions, time, and space. However, integrating multi-sample data in a unified way to explore cellular heterogeneity remains challenging. Here, we present Stereopy, a flexible framework for modeling and dissecting comparative and spatiotemporal patterns in multi-sample spatial transcriptomics with interactive data visualization. To optimize this framework, we devise a universal container, a scope controller, and an integrative transformer tailored for multi-sample multimodal data storage, management, and processing. Stereopy showcases three representative applications: investigating specific cell communities and genes responsible for pathological changes, detecting spatiotemporal gene patterns by considering spatial and temporal features, and inferring three-dimensional niche-based cell-gene interaction network that bridges intercellular communications and intracellular regulations. Stereopy serves as both a comprehensive bioinformatics toolbox and an extensible framework that empowers researchers with enhanced data interpretation abilities and new perspectives for mining multi-sample spatial transcriptomics data.