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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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    as
    1. Shijia Zhu & Naoto Kubota & Shidan Wang & Tao Wang & Guanghua Xiao & Yujin Hoshida, 2024. "STIE: Single-cell level deconvolution, convolution, and clustering in in situ capturing-based spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Ed S. Lein & Michael J. Hawrylycz & Nancy Ao & Mikael Ayres & Amy Bensinger & Amy Bernard & Andrew F. Boe & Mark S. Boguski & Kevin S. Brockway & Emi J. Byrnes & Lin Chen & Li Chen & Tsuey-Ming Chen &, 2007. "Genome-wide atlas of gene expression in the adult mouse brain," Nature, Nature, vol. 445(7124), pages 168-176, January.
    3. Xiyue Wang & Junhan Zhao & Eliana Marostica & Wei Yuan & Jietian Jin & Jiayu Zhang & Ruijiang Li & Hongping Tang & Kanran Wang & Yu Li & Fang Wang & Yulong Peng & Junyou Zhu & Jing Zhang & Christopher, 2024. "A pathology foundation model for cancer diagnosis and prognosis prediction," Nature, Nature, vol. 634(8035), pages 970-978, October.
    4. Kazumasa Kanemaru & James Cranley & Daniele Muraro & Antonio M. A. Miranda & Siew Yen Ho & Anna Wilbrey-Clark & Jan Patrick Pett & Krzysztof Polanski & Laura Richardson & Monika Litvinukova & Natsuhik, 2023. "Spatially resolved multiomics of human cardiac niches," Nature, Nature, vol. 619(7971), pages 801-810, July.
    5. Amanda Janesick & Robert Shelansky & Andrew D. Gottscho & Florian Wagner & Stephen R. Williams & Morgane Rouault & Ghezal Beliakoff & Carolyn A. Morrison & Michelli F. Oliveira & Jordan T. Sicherman &, 2023. "High resolution mapping of the tumor microenvironment using integrated single-cell, spatial and in situ analysis," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Duy Pham & Xiao Tan & Brad Balderson & Jun Xu & Laura F. Grice & Sohye Yoon & Emily F. Willis & Minh Tran & Pui Yeng Lam & Arti Raghubar & Priyakshi Kalita-de Croft & Sunil Lakhani & Jana Vukovic & Ma, 2023. "Robust mapping of spatiotemporal trajectories and cell–cell interactions in healthy and diseased tissues," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    7. Hao Xu & Shuyan Wang & Minghao Fang & Songwen Luo & Chunpeng Chen & Siyuan Wan & Rirui Wang & Meifang Tang & Tian Xue & Bin Li & Jun Lin & Kun Qu, 2023. "SPACEL: deep learning-based characterization of spatial transcriptome architectures," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    8. Yuchen Liang & Guowei Shi & Runlin Cai & Yuchen Yuan & Ziying Xie & Long Yu & Yingjian Huang & Qian Shi & Lizhe Wang & Jun Li & Zhonghui Tang, 2024. "PROST: quantitative identification of spatially variable genes and domain detection in spatial transcriptomics," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Christoph Kuppe & Ricardo O. Ramirez Flores & Zhijian Li & Sikander Hayat & Rebecca T. Levinson & Xian Liao & Monica T. Hannani & Jovan Tanevski & Florian Wünnemann & James S. Nagai & Maurice Halder &, 2022. "Spatial multi-omic map of human myocardial infarction," Nature, Nature, vol. 608(7924), pages 766-777, August.
    10. Hanwen Xu & Naoto Usuyama & Jaspreet Bagga & Sheng Zhang & Rajesh Rao & Tristan Naumann & Cliff Wong & Zelalem Gero & Javier González & Yu Gu & Yanbo Xu & Mu Wei & Wenhui Wang & Shuming Ma & Furu Wei , 2024. "A whole-slide foundation model for digital pathology from real-world data," Nature, Nature, vol. 630(8015), pages 181-188, June.
    11. Thomas Wohlfahrt & Simon Rauber & Steffen Uebe & Markus Luber & Alina Soare & Arif Ekici & Stefanie Weber & Alexandru-Emil Matei & Chih-Wei Chen & Christiane Maier & Emmanuel Karouzakis & Hans P. Kien, 2019. "PU.1 controls fibroblast polarization and tissue fibrosis," Nature, Nature, vol. 566(7744), pages 344-349, February.
    12. Jun Ma & Yuting He & Feifei Li & Lin Han & Chenyu You & Bo Wang, 2024. "Segment anything in medical images," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
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