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Liu, Junzhuo ; Eckstein, Markus ; Wang, Zhixiang ; Feuerhake, Friedrich ; Merhof, Dorit

Spatial transcriptomics expression prediction from histopathology based on cross-modal mask reconstruction and contrastive learning

Liu, Junzhuo, Eckstein, Markus, Wang, Zhixiang, Feuerhake, Friedrich and Merhof, Dorit (2025) Spatial transcriptomics expression prediction from histopathology based on cross-modal mask reconstruction and contrastive learning. Medical Image Analysis 108, p. 103889.

Date of publication of this fulltext: 03 Dec 2025 05:41
Article
DOI to cite this document: 10.5283/epub.78252


Abstract

Spatial transcriptomics is a technology that captures gene expression at different spatial locations, widely used in tumor microenvironment analysis and molecular profiling of histopathology, providing valuable insights into resolving gene expression and clinical diagnosis of cancer. Due to the high cost of data acquisition, large-scale spatial transcriptomics data remain challenging to obtain. ...

Spatial transcriptomics is a technology that captures gene expression at different spatial locations, widely used in tumor microenvironment analysis and molecular profiling of histopathology, providing valuable insights into resolving gene expression and clinical diagnosis of cancer. Due to the high cost of data acquisition, large-scale spatial transcriptomics data remain challenging to obtain. In this study, we develop a contrastive learning-based deep learning method to predict spatially resolved gene expression from the whole-slide images (WSIs). Unlike existing end-to-end prediction frameworks, our method leverages multi-modal contrastive learning to establish a correspondence between histopathological morphology and spatial gene expression in the feature space. By computing cross-modal feature similarity, our method generates spatially resolved gene expression directly from WSIs. Furthermore, to enhance the standard contrastive learning paradigm, a cross-modal masked reconstruction is designed as a pretext task, enabling feature-level fusion between modalities. Notably, our method does not rely on large-scale pretraining datasets or abstract semantic representations from either modality, making it particularly effective for scenarios with limited spatial transcriptomics data. Evaluation across six different disease datasets demonstrates that, compared to existing studies, our method improves Pearson Correlation Coefficient (PCC) in the prediction of highly expressed genes, highly variable genes, and marker genes by 6.27 %, 6.11 %, and 11.26 % respectively. Further analysis indicates that our method preserves gene-gene correlations and applies to datasets with limited samples. Additionally, our method exhibits potential in cancer tissue localization based on biomarker expression. The code repository for this work is available at https://github.com/ngfufdrdh/CMRCNet.



Involved Institutions


Details

Item typeArticle
Journal or Publication TitleMedical Image Analysis
Publisher:Elsevier
Volume:108
Page Range:p. 103889
Date25 November 2025
InstitutionsInformatics and Data Science > Department Computational Life Science
Informatics and Data Science > Department Computational Life Science > Chair of Image Analysis and Computer Vision (Prof. Dr.-Ing. Dorit Merhof)
Identification Number
ValueType
10.1016/j.media.2025.103889DOI
KeywordsHistopathology, Spatial transcriptomics, Contrastive learning, Multimodal fusion
Dewey Decimal Classification000 Computer science, information & general works > 004 Computer science
StatusPublished
RefereedYes, this version has been refereed
Created at the University of RegensburgPartially
URN of the UB Regensburgurn:nbn:de:bvb:355-epub-782528
Item ID78252

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