A Large-Scale Benchmark of Cross-Modal Learning for Histology and Gene Expression in Spatial Transcriptomics

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Auteurs principaux: Gindra, Rushin H., Palla, Giovanni, Nguyen, Mathias, Wagner, Sophia J., Tran, Manuel, Theis, Fabian J, Saur, Dieter, Crawford, Lorin, Peng, Tingying
Format: Preprint
Publié: 2025
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author Gindra, Rushin H.
Palla, Giovanni
Nguyen, Mathias
Wagner, Sophia J.
Tran, Manuel
Theis, Fabian J
Saur, Dieter
Crawford, Lorin
Peng, Tingying
author_facet Gindra, Rushin H.
Palla, Giovanni
Nguyen, Mathias
Wagner, Sophia J.
Tran, Manuel
Theis, Fabian J
Saur, Dieter
Crawford, Lorin
Peng, Tingying
contents Spatial transcriptomics enables simultaneous measurement of gene expression and tissue morphology, offering unprecedented insights into cellular organization and disease mechanisms. However, the field lacks comprehensive benchmarks for evaluating multimodal learning methods that leverage both histology images and gene expression data. Here, we present HESCAPE, a large-scale benchmark for cross-modal contrastive pretraining in spatial transcriptomics, built on a curated pan-organ dataset spanning 6 different gene panels and 54 donors. We systematically evaluated state-of-the-art image and gene expression encoders across multiple pretraining strategies and assessed their effectiveness on two downstream tasks: gene mutation classification and gene expression prediction. Our benchmark demonstrates that gene expression encoders are the primary determinant of strong representational alignment, and that gene models pretrained on spatial transcriptomics data outperform both those trained without spatial data and simple baseline approaches. However, downstream task evaluation reveals a striking contradiction: while contrastive pretraining consistently improves gene mutation classification performance, it degrades direct gene expression prediction compared to baseline encoders trained without cross-modal objectives. We identify batch effects as a key factor that interferes with effective cross-modal alignment. Our findings highlight the critical need for batch-robust multimodal learning approaches in spatial transcriptomics. To accelerate progress in this direction, we release HESCAPE, providing standardized datasets, evaluation protocols, and benchmarking tools for the community
format Preprint
id arxiv_https___arxiv_org_abs_2508_01490
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle A Large-Scale Benchmark of Cross-Modal Learning for Histology and Gene Expression in Spatial Transcriptomics
Gindra, Rushin H.
Palla, Giovanni
Nguyen, Mathias
Wagner, Sophia J.
Tran, Manuel
Theis, Fabian J
Saur, Dieter
Crawford, Lorin
Peng, Tingying
Genomics
Artificial Intelligence
Computer Vision and Pattern Recognition
Machine Learning
Tissues and Organs
Applications
Spatial transcriptomics enables simultaneous measurement of gene expression and tissue morphology, offering unprecedented insights into cellular organization and disease mechanisms. However, the field lacks comprehensive benchmarks for evaluating multimodal learning methods that leverage both histology images and gene expression data. Here, we present HESCAPE, a large-scale benchmark for cross-modal contrastive pretraining in spatial transcriptomics, built on a curated pan-organ dataset spanning 6 different gene panels and 54 donors. We systematically evaluated state-of-the-art image and gene expression encoders across multiple pretraining strategies and assessed their effectiveness on two downstream tasks: gene mutation classification and gene expression prediction. Our benchmark demonstrates that gene expression encoders are the primary determinant of strong representational alignment, and that gene models pretrained on spatial transcriptomics data outperform both those trained without spatial data and simple baseline approaches. However, downstream task evaluation reveals a striking contradiction: while contrastive pretraining consistently improves gene mutation classification performance, it degrades direct gene expression prediction compared to baseline encoders trained without cross-modal objectives. We identify batch effects as a key factor that interferes with effective cross-modal alignment. Our findings highlight the critical need for batch-robust multimodal learning approaches in spatial transcriptomics. To accelerate progress in this direction, we release HESCAPE, providing standardized datasets, evaluation protocols, and benchmarking tools for the community
title A Large-Scale Benchmark of Cross-Modal Learning for Histology and Gene Expression in Spatial Transcriptomics
topic Genomics
Artificial Intelligence
Computer Vision and Pattern Recognition
Machine Learning
Tissues and Organs
Applications
url https://arxiv.org/abs/2508.01490