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Thor: a platform for cell-level investigation of spatial transcriptomics and histology

Author

Listed:
  • Pengzhi Zhang

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

  • Weiqing Chen

    (Houston Methodist Research Institute
    Cornell University)

  • Tu N. Tran

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

  • Minghao Zhou

    (University of Florida)

  • Kaylee N. Carter

    (Houston Methodist Research Institute)

  • Ibrahem Kandel

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

  • Shengyu Li

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

  • Xen Ping Hoi

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Cedars-Sinai Medical Center)

  • Yuxing Sun

    (Georgia Institute of Technology)

  • Li Lai

    (Houston Methodist Research Institute)

  • Keith Youker

    (Houston Methodist Research Institute)

  • Qianqian Song

    (University of Florida)

  • Yu Yang

    (University of Florida)

  • Fotis Nikolos

    (Houston Methodist Research Institute
    Houston Methodist Research Institute)

  • Zejuan Li

    (Houston Methodist Research Institute
    Weill Cornell Medical College)

  • Keith Syson Chan

    (Houston Methodist Research Institute
    Houston Methodist Research Institute)

  • John P. Cooke

    (Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

  • Guangyu Wang

    (Houston Methodist Research Institute
    Houston Methodist Research Institute
    Cornell University
    Houston Methodist Research Institute)

Abstract

Spatial transcriptomics links gene expression with tissue morphology, however, current tools often prioritize genomic analysis, lacking integrated image interpretation. To address this, we present Thor, a comprehensive platform for cell-level analysis of spatial transcriptomics and histological images. Thor employs an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptome from spot-level data, effectively combining gene expression and cell morphology. The platform includes 10 modular tools for genomic and image-based analysis, and is paired with Mjolnir, a web-based interface for interactive exploration of gigapixel images. Thor is validated on simulated data and multiple spatial platforms (ISH, MERFISH, Xenium, Stereo-seq). Thor characterizes regenerative signatures in heart failure, screens breast cancer hallmarks, resolves fine layers in mouse olfactory bulb, and annotates fibrotic heart tissue. In high-resolution Visium HD data, it enhances spatial gene patterns aligned with histology. By bridging transcriptomic and histological analysis, Thor enables holistic tissue interpretation in spatial biology.

Suggested Citation

  • Pengzhi Zhang & Weiqing Chen & Tu N. Tran & Minghao Zhou & Kaylee N. Carter & Ibrahem Kandel & Shengyu Li & Xen Ping Hoi & Yuxing Sun & Li Lai & Keith Youker & Qianqian Song & Yu Yang & Fotis Nikolos , 2025. "Thor: a platform for cell-level investigation of spatial transcriptomics and histology," Nature Communications, Nature, vol. 16(1), pages 1-22, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62593-1
    DOI: 10.1038/s41467-025-62593-1
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