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PreprintCC BY-NC-NDbioRxiv

ASTRA enables zero-shot super-resolution of spatial transcriptomics across capture geometries

  1. 1Peking University

Abstract

Spatial transcriptomic super-resolution recovers tissue organization obscured by coarse sampling, but fitting a model to each section greatly increases computational cost and reduces practicality. We introduce ASTRA, a cross-platform pretrained model that reconstructs expression from histology and measured RNA by zero-shot inference. Training with arbitrarily shaped count-bearing regions, termed parents, enables one frozen model to accommodate dense bins and separated spots. Across six held-out Visium HD sections, ASTRA achieved higher correlations under dense-bin and pseudo-Visium sampling, lower dense-bin errors and substantially shorter processing times than existing methods. It improved colorectal tissue segmentation and tumor-boundary recovery. In real colorectal Visium, reconstruction spatially resolved a stromal transcriptional state supported by measured RNA. The same checkpoint supported regional and nucleus-associated analyses across 43 invasive lobular carcinoma sections and within-spot interpretation across 92 triple-negative breast cancer sections. ASTRA establishes a reusable framework for practical, cohort-scale spatial transcriptomic super-resolution across platforms.

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BibTeX
@misc{ye2026astra,
  title = {{ASTRA enables zero-shot super-resolution of spatial transcriptomics across capture geometries}},
  author = {J. Ye and Q. Cui},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.30.755663},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.30.755663v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - ASTRA enables zero-shot super-resolution of spatial transcriptomics across capture geometries
AU  - J. Ye
AU  - Q. Cui
PY  - 2026
DA  - 2026/09/30
PB  - bioRxiv
DO  - 10.64898/2026.09.30.755663
UR  - https://www.biorxiv.org/content/10.64898/2026.09.30.755663v1
AB  - Spatial transcriptomic super-resolution recovers tissue organization obscured by coarse sampling, but fitting a model to each section greatly increases computational cost and reduces practicality. We introduce ASTRA, a cross-platform pretrained model that reconstructs expression from histology and measured RNA by zero-shot inference. Training with arbitrarily shaped count-bearing regions, termed parents, enables one frozen model to accommodate dense bins and separated spots. Across six held-out Visium HD sections, ASTRA achieved higher correlations under dense-bin and pseudo-Visium sampling, lower dense-bin errors and substantially shorter processing times than existing methods. It improved colorectal tissue segmentation and tumor-boundary recovery. In real colorectal Visium, reconstruction spatially resolved a stromal transcriptional state supported by measured RNA. The same checkpoint supported regional and nucleus-associated analyses across 43 invasive lobular carcinoma sections and within-spot interpretation across 92 triple-negative breast cancer sections. ASTRA establishes a reusable framework for practical, cohort-scale spatial transcriptomic super-resolution across platforms.
ER  -