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

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; Zejuan Li; Keith Syson Chan; John P Cooke; Guangyu Wang

doi:10.1038/s41467-025-62593-1

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

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, Zejuan Li, Keith Syson Chan, John P Cooke, Guangyu Wang

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Article number	7178
Pages (from-to)	7178
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-62593-1
State	Published - Aug 5 2025

Keywords

Animals
Mice
Transcriptome/genetics
Gene Expression Profiling/methods
Humans
Single-Cell Analysis/methods
Image Processing, Computer-Assisted/methods
Software
Breast Neoplasms/genetics
Female

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General
General Physics and Astronomy

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Zhang, P., Chen, W., Tran, T. N., Zhou, M., Carter, K. N., Kandel, I., Li, S., Hoi, X. P., Sun, Y., Lai, L., Youker, K., Song, Q., Yang, Y., Nikolos, F., Li, Z., Chan, K. S., Cooke, J. P., & Wang, G. (2025). Thor: a platform for cell-level investigation of spatial transcriptomics and histology. Nature Communications, 16(1), 7178. Article 7178. https://doi.org/10.1038/s41467-025-62593-1

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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.",

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doi = "10.1038/s41467-025-62593-1",

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AU - Chen, Weiqing

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AU - Zhou, Minghao

AU - Carter, Kaylee N

AU - Kandel, Ibrahem

AU - Li, Shengyu

AU - Hoi, Xen Ping

AU - Sun, Yuxing

AU - Lai, Li

AU - Youker, Keith

AU - Song, Qianqian

AU - Yang, Yu

AU - Nikolos, Fotis

AU - Li, Zejuan

AU - Chan, Keith Syson

AU - Cooke, John P

AU - Wang, Guangyu

N1 - Publisher Copyright: © The Author(s) 2025.

PY - 2025/8/5

Y1 - 2025/8/5

N2 - 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.

AB - 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.

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KW - Transcriptome/genetics

KW - Gene Expression Profiling/methods

KW - Humans

KW - Single-Cell Analysis/methods

KW - Image Processing, Computer-Assisted/methods

KW - Software

KW - Breast Neoplasms/genetics

KW - Female

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JO - Nature Communications

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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