Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis

Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spati...

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Main Authors: Yongxin Ge, Jiake Leng, Ziyang Tang, Kanran Wang, Kaicheng U, Sophia Meixuan Zhang, Sen Han, Yiyan Zhang, Jinxi Xiang, Sen Yang, Xiang Liu, Yi Song, Xiyue Wang, Yuchen Li, Junhan Zhao
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0568
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author Yongxin Ge
Jiake Leng
Ziyang Tang
Kanran Wang
Kaicheng U
Sophia Meixuan Zhang
Sen Han
Yiyan Zhang
Jinxi Xiang
Sen Yang
Xiang Liu
Yi Song
Xiyue Wang
Yuchen Li
Junhan Zhao
author_facet Yongxin Ge
Jiake Leng
Ziyang Tang
Kanran Wang
Kaicheng U
Sophia Meixuan Zhang
Sen Han
Yiyan Zhang
Jinxi Xiang
Sen Yang
Xiang Liu
Yi Song
Xiyue Wang
Yuchen Li
Junhan Zhao
author_sort Yongxin Ge
collection DOAJ
description Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spatial localization, with limited emphasis on leveraging rich histopathological insights from staining images. We introduce GIST, a deep learning-enabled gene expression and histology integration for spatial cellular profiling. GIST employs histopathology foundation models pretrained on millions of histology images to enhance feature extraction and a hybrid graph transformer model to integrate them with transcriptome features. Validated with datasets from human lung, breast, and colorectal cancers, GIST effectively reveals spatial domains and substantially improves the accuracy of segmenting the microenvironment after denoising transcriptomics data. This enhancement enables more accurate gene expression analysis and aids in identifying prognostic marker genes, outperforming state-of-the-art deep learning methods with a total improvement of up to 49.72%. GIST provides a generalizable framework for integrating histology with spatial transcriptome analysis, revealing novel insights into spatial organization and functional dynamics.
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institution Kabale University
issn 2639-5274
language English
publishDate 2025-01-01
publisher American Association for the Advancement of Science (AAAS)
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spelling doaj-art-eb9c0cd266c743019d588f03959d78472025-01-17T08:00:36ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0568Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile AnalysisYongxin Ge0Jiake Leng1Ziyang Tang2Kanran Wang3Kaicheng U4Sophia Meixuan Zhang5Sen Han6Yiyan Zhang7Jinxi Xiang8Sen Yang9Xiang Liu10Yi Song11Xiyue Wang12Yuchen Li13Junhan Zhao14School of Big Data and Software Engineering, Chongqing University, Chongqing, China.School of Big Data and Software Engineering, Chongqing University, Chongqing, China.Department of Computer and Information Technology, Purdue University, West Lafayette, IN, USA.Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, China.Tri-Institutional Computational Biology & Medicine, Weill Cornell Medicine, New York, NY, USA.College of Agriculture and Life Sciences, Cornell University, Ithaca, NY, USA.Division of Genetics, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA.Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.Department of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, IN, USA.Department of Neurosurgery, Chongqing University Three Gorges Hospital, Chongqing, China.Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.Spatially resolved transcriptomics enable comprehensive measurement of gene expression at subcellular resolution while preserving the spatial context of the tissue microenvironment. While deep learning has shown promise in analyzing SCST datasets, most efforts have focused on sequence data and spatial localization, with limited emphasis on leveraging rich histopathological insights from staining images. We introduce GIST, a deep learning-enabled gene expression and histology integration for spatial cellular profiling. GIST employs histopathology foundation models pretrained on millions of histology images to enhance feature extraction and a hybrid graph transformer model to integrate them with transcriptome features. Validated with datasets from human lung, breast, and colorectal cancers, GIST effectively reveals spatial domains and substantially improves the accuracy of segmenting the microenvironment after denoising transcriptomics data. This enhancement enables more accurate gene expression analysis and aids in identifying prognostic marker genes, outperforming state-of-the-art deep learning methods with a total improvement of up to 49.72%. GIST provides a generalizable framework for integrating histology with spatial transcriptome analysis, revealing novel insights into spatial organization and functional dynamics.https://spj.science.org/doi/10.34133/research.0568
spellingShingle Yongxin Ge
Jiake Leng
Ziyang Tang
Kanran Wang
Kaicheng U
Sophia Meixuan Zhang
Sen Han
Yiyan Zhang
Jinxi Xiang
Sen Yang
Xiang Liu
Yi Song
Xiyue Wang
Yuchen Li
Junhan Zhao
Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis
Research
title Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis
title_full Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis
title_fullStr Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis
title_full_unstemmed Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis
title_short Deep Learning-Enabled Integration of Histology and Transcriptomics for Tissue Spatial Profile Analysis
title_sort deep learning enabled integration of histology and transcriptomics for tissue spatial profile analysis
url https://spj.science.org/doi/10.34133/research.0568
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