Thor: a platform for cell-level investigation of spatial transcriptomics and histology
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.
Authors
- Keith A. Youker (ORCID: https://orcid.org/0000-0003-2535-7973)
- Minghao Zhou
- Zejuan Li (ORCID: https://orcid.org/0000-0002-2714-8940)
- Fotis Nikolos (ORCID: https://orcid.org/0000-0002-8622-0017)
- Keith Syson Chan (ORCID: https://orcid.org/0000-0003-1670-8508)
- John P. Cooke (ORCID: https://orcid.org/0000-0003-0033-9138)
- Xen Ping Hoi (ORCID: https://orcid.org/0000-0001-7610-7291)
- K. Carter (ORCID: https://orcid.org/0009-0002-8920-3033)
- Weiqing Chen (ORCID: https://orcid.org/0000-0003-3539-9210)
- Pengzhi Zhang (ORCID: https://orcid.org/0000-0001-6920-1490)
- Yuxing Sun
- Li Lai (ORCID: https://orcid.org/0000-0002-5731-2705)
- Guangyu Wang (ORCID: https://orcid.org/0000-0003-4803-7200)
- Qianqian Song (ORCID: https://orcid.org/0000-0002-4455-5302)
- Tu Tran
- Yu Yang
- Shengyu Li
- Ibrahem Kandel
Institutions
- Cedars-Sinai Medical Center (US)
- Houston Methodist (US)
- Georgia Institute of Technology (US)
- Cornell University (US)
- University of Florida Health (US)
- University of Florida (US)
- Methodist Hospital (US)
- Methodist Hospital (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-05
- DOI
- https://doi.org/10.1038/s41467-025-62593-1
- Citations
- 9
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 7.25
Funders
- Cancer Prevention and Research Institute of Texas
- National Heart, Lung, and Blood Institute
- National Cancer Institute
- National Institute of General Medical Sciences