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PreprintCC BYbioRxiv

THiRST: Computer Vision Empowered Three-dimensional High-Resolution Spatial Transcriptomics Analytics

  1. 1Vanderbilt University

Abstract

High-resolution spatial transcriptomics (ST) preserves gene expression within tissue architecture but remains limited to individual two-dimensional (2D) sections, restricting analysis of continuous three-dimensional (3D) structures and cross-section consistency. We present THiRST, a computational framework for reconstructing multi-resolution 3D spatial transcriptomic representations from serial sections. THiRST combines coarse-to-fine morphology-guided registration, spatial matching of ST units, cross-section association of segmented structures, and integration of Visium V2 and high-definition ST. In serial kidney sections, patch-level refinement increased the same-cluster proportions of matched units at adjacent offsets from 63.8% and 65.6% to 70.7% and 70.0%, respectively, while improving expression concordance. The reconstructed correspondences enabled 3D glomerular and object-level expression analysis, with 54.1% of differential genes detected only in 3D. Cross-platform integration further aligned V2 and high-definition measurements in a shared expression space. THiRST demonstrates the feasibility of object-level 3D ST analysis from serial 2D sections and underscores the importance of accurate local registration.

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BibTeX
@misc{zhu2026thirst,
  title = {{THiRST: Computer Vision Empowered Three-dimensional High-Resolution Spatial Transcriptomics Analytics}},
  author = {J. Zhu and Y. Wang and Z. Lu and C. Qu and Y. Zhu and Y. Yang and S. Zhao and H. Yang and Y. Huo and R. Deng},
  howpublished = {bioRxiv},
  year = {2026},
  month = oct,
  doi = {10.64898/2026.10.29.762926},
  url = {https://www.biorxiv.org/content/10.64898/2026.10.29.762926v1},
  note = {CC BY},
}
RIS
TY  - UNPB
TI  - THiRST: Computer Vision Empowered Three-dimensional High-Resolution Spatial Transcriptomics Analytics
AU  - J. Zhu
AU  - Y. Wang
AU  - Z. Lu
AU  - C. Qu
AU  - Y. Zhu
AU  - Y. Yang
AU  - S. Zhao
AU  - H. Yang
AU  - Y. Huo
AU  - R. Deng
PY  - 2026
DA  - 2026/10/29
PB  - bioRxiv
DO  - 10.64898/2026.10.29.762926
UR  - https://www.biorxiv.org/content/10.64898/2026.10.29.762926v1
AB  - High-resolution spatial transcriptomics (ST) preserves gene expression within tissue architecture but remains limited to individual two-dimensional (2D) sections, restricting analysis of continuous three-dimensional (3D) structures and cross-section consistency. We present THiRST, a computational framework for reconstructing multi-resolution 3D spatial transcriptomic representations from serial sections. THiRST combines coarse-to-fine morphology-guided registration, spatial matching of ST units, cross-section association of segmented structures, and integration of Visium V2 and high-definition ST. In serial kidney sections, patch-level refinement increased the same-cluster proportions of matched units at adjacent offsets from 63.8% and 65.6% to 70.7% and 70.0%, respectively, while improving expression concordance. The reconstructed correspondences enabled 3D glomerular and object-level expression analysis, with 54.1% of differential genes detected only in 3D. Cross-platform integration further aligned V2 and high-definition measurements in a shared expression space. THiRST demonstrates the feasibility of object-level 3D ST analysis from serial 2D sections and underscores the importance of accurate local registration.
ER  -