ST-GEARS: Advancing 3D downstream research through accurate spatial information recovery

Tianyi Xia, Luni Hu, Lulu Zuo, Lei Cao, Yunjia Zhang, Mengyang Xu, Qin Lu, Lei Zhang, Taotao Pan, Bohan Zhang, Bowen Ma, Chuan Chen, Junfu Guo, Chang Shi, Mei Li, Chao Liu (), Yuxiang Li (), Yong Zhang () and Shuangsang Fang ()
Additional contact information
Tianyi Xia: BGI Research
Luni Hu: BGI Research
Lulu Zuo: BGI
Lei Cao: BGI Research
Yunjia Zhang: BGI Research
Mengyang Xu: BGI Research
Qin Lu: BGI Research
Lei Zhang: BGI Research
Taotao Pan: BGI Research
Bohan Zhang: BGI Research
Bowen Ma: BGI Research
Chuan Chen: BGI Research
Junfu Guo: BGI
Chang Shi: BGI
Mei Li: BGI Research
Chao Liu: BGI Research
Yuxiang Li: BGI Research
Yong Zhang: BGI Research
Shuangsang Fang: BGI Research

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Three-dimensional Spatial Transcriptomics has revolutionized our understanding of tissue regionalization, organogenesis, and development. However, existing approaches overlook either spatial information or experiment-induced distortions, leading to significant discrepancies between reconstruction results and in vivo cell locations, causing unreliable downstream analysis. To address these challenges, we propose ST-GEARS (Spatial Transcriptomics GEospatial profile recovery system through AnchoRS). By employing innovative Distributive Constraints into the Optimization scheme, ST-GEARS retrieves anchors with exceeding precision that connect closest spots across sections in vivo. Guided by the anchors, it first rigidly aligns sections, next solves and denoises Elastic Fields to counteract distortions. Through mathematically proved Bi-sectional Fields Application, it eventually recovers the original spatial profile. Studying ST-GEARS across number of sections, sectional distances and sequencing platforms, we observed its outstanding performance on tissue, cell, and gene levels. ST-GEARS provides precise and well-explainable ‘gears’ between in vivo situations and in vitro analysis, powerfully fueling potential of biological discoveries.

Date: 2024
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DOI: 10.1038/s41467-024-51935-0

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