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Leveraging information in spatial transcriptomics to predict super-resolution gene expression from histology images in tumors
Open accessAbstract
Recent developments in spatial transcriptomics (ST) technologies have enabled the profiling of transcriptome-wide gene expression while retaining the location information of measured genes within tissues. Moreover, the corresponding high-resolution hematoxylin and eosin-stained histology images are readily available for the ST tissue sections. Since histology images are easy to obtain, it is desirable to leverage information learned from ST to predict gene expression for tissue sections where only histology images are available. Here we present HisToGene, a deep learning model for gene expression prediction from histology images. To account for the spatial dependency of measured spots, HisToGene adopts Vision Transformer, a state-of-the-art method for image recognition. The well-trained HisToGene model can also predict super-resolution gene expression. Through evaluations on 32 HER2+ breast cancer samples with 9,612 spots and 785 genes, we show that HisToGene accurately predicts gene expression and outperforms ST-Net both in gene expression prediction and clustering tissue regions using the predicted expression. We further show that the predicted super-resolution gene expression also leads to higher clustering accuracy than observed gene expression. Gene expression predicted from HisToGene enables researchers to generate virtual transcriptomics data at scale and can help elucidate the molecular signatures of tissues.
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“Several studies have explored predicting gene expression from H&E images using AI models59–62.”
From A visual–omics foundation model to bridge histopathology with spatial transcriptomics (2025) · cites this paper as [59]
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Advances in predicting omics profiles from imaging data
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Data enhancement in the age of spatial biology
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Metadata
- Authors
- Pang, M., Su, K., & Li, M.
- Affiliations
- King Abdullah University of Science and Technology (SA)
- University of Pennsylvania (US)
- Corresponding author
- Su, Kenong
- Li, Mingyao
- Venue
- bioRxiv (Cold Spring Harbor Laboratory)
- Publisher
- openRxiv
- Published
- 2021-11-28
- OpenAlex
- W3216067893
- Cited by
- 130
- References
- 37
- Citations by year
- 2026: 35 · 2025: 49 · 2024: 28 · 2023: 13 · 2022: 5
- Type
- posted content
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
- Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
- Keywords
- spatial transcriptomics, HER2-positive breast cancer, vision transformer, tumor molecular signatures
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