Reconstruction of the cell pseudo-space from single-cell RNA sequencing data with scSpace

Jingyang Qian, Jie Liao (), Ziqi Liu, Ying Chi, Yin Fang, Yanrong Zheng, Xin Shao, Bingqi Liu, Yongjin Cui, Wenbo Guo, Yining Hu, Hudong Bao, Penghui Yang, Qian Chen, Mingxiao Li, Bing Zhang () and Xiaohui Fan ()
Additional contact information
Jingyang Qian: Zhejiang University
Jie Liao: Zhejiang University
Ziqi Liu: Zhejiang University
Ying Chi: DAMO Academy, Alibaba group
Yin Fang: Zhejiang University
Yanrong Zheng: Zhejiang University
Xin Shao: Zhejiang University
Bingqi Liu: Zhejiang University
Yongjin Cui: Zhejiang University
Wenbo Guo: Zhejiang University
Yining Hu: Zhejiang University
Hudong Bao: Zhejiang University
Penghui Yang: Zhejiang University
Qian Chen: Zhejiang University
Mingxiao Li: Institute of Microelectronics of the Chinese Academy of Sciences
Bing Zhang: DAMO Academy, Alibaba group
Xiaohui Fan: Zhejiang University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Tissues are highly complicated with spatial heterogeneity in gene expression. However, the cutting-edge single-cell RNA-seq technology eliminates the spatial information of individual cells, which contributes to the characterization of cell identities. Herein, we propose single-cell spatial position associated co-embeddings (scSpace), an integrative method to identify spatially variable cell subpopulations by reconstructing cells onto a pseudo-space with spatial transcriptome references (Visium, STARmap, Slide-seq, etc.). We benchmark scSpace with both simulated and biological datasets, and demonstrate that scSpace can accurately and robustly identify spatially variated cell subpopulations. When employed to reconstruct the spatial architectures of complex tissue such as the brain cortex, the small intestinal villus, the liver lobule, the kidney, the embryonic heart, and others, scSpace shows promising performance on revealing the pairwise cellular spatial association within single-cell data. The application of scSpace in melanoma and COVID-19 exhibits a broad prospect in the discovery of spatial therapeutic markers.

Date: 2023
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DOI: 10.1038/s41467-023-38121-4

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