PAST: A multimodal single-cell foundation model for histopathology and spatial transcriptomics in cancer

Fuente: arXiv
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Autori principali: Yang, Changchun, Li, Haoyang, Wu, Yushuai, Zhang, Yilan, Jiao, Yifeng, Zhang, Yu, Huang, Rihan, Cheng, Yuan, Qi, Yuan, Guo, Xin, Gao, Xin
Natura: Preprint
Pubblicazione: 2025
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author Yang, Changchun
Li, Haoyang
Wu, Yushuai
Zhang, Yilan
Jiao, Yifeng
Zhang, Yu
Huang, Rihan
Cheng, Yuan
Qi, Yuan
Guo, Xin
Gao, Xin
author_facet Yang, Changchun
Li, Haoyang
Wu, Yushuai
Zhang, Yilan
Jiao, Yifeng
Zhang, Yu
Huang, Rihan
Cheng, Yuan
Qi, Yuan
Guo, Xin
Gao, Xin
contents While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.
format Preprint
id arxiv_https___arxiv_org_abs_2507_06418
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle PAST: A multimodal single-cell foundation model for histopathology and spatial transcriptomics in cancer
Yang, Changchun
Li, Haoyang
Wu, Yushuai
Zhang, Yilan
Jiao, Yifeng
Zhang, Yu
Huang, Rihan
Cheng, Yuan
Qi, Yuan
Guo, Xin
Gao, Xin
Quantitative Methods
Computer Vision and Pattern Recognition
Applications
While pathology foundation models have transformed cancer image analysis, they often lack integration with molecular data at single-cell resolution, limiting their utility for precision oncology. Here, we present PAST, a pan-cancer single-cell foundation model trained on 20 million paired histopathology images and single-cell transcriptomes spanning multiple tumor types and tissue contexts. By jointly encoding cellular morphology and gene expression, PAST learns unified cross-modal representations that capture both spatial and molecular heterogeneity at the cellular level. This approach enables accurate prediction of single-cell gene expression, virtual molecular staining, and multimodal survival analysis directly from routine pathology slides. Across diverse cancers and downstream tasks, PAST consistently exceeds the performance of existing approaches, demonstrating robust generalizability and scalability. Our work establishes a new paradigm for pathology foundation models, providing a versatile tool for high-resolution spatial omics, mechanistic discovery, and precision cancer research.
title PAST: A multimodal single-cell foundation model for histopathology and spatial transcriptomics in cancer
topic Quantitative Methods
Computer Vision and Pattern Recognition
Applications
url https://arxiv.org/abs/2507.06418