SIGMMA: Hierarchical Graph-Based Multi-Scale Multi-modal Contrastive Alignment of Histopathology Image and Spatial Transcriptome

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Auteurs principaux: Jeong, Dabin, Vahidi, Amirhossein, Ramírez-Suástegui, Ciro, Moullet, Marie, Ly, Kevin, Sanian, Mohammad Vali, Birk, Sebastian, Chang, Yinshui, Boxall, Adam, Jafree, Daniyal, Steele, Lloyd, MS, Vijaya Baskar, Haniffa, Muzlifah, Lotfollahi, Mohammad
Format: Preprint
Publié: 2025
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author Jeong, Dabin
Vahidi, Amirhossein
Ramírez-Suástegui, Ciro
Moullet, Marie
Ly, Kevin
Sanian, Mohammad Vali
Birk, Sebastian
Chang, Yinshui
Boxall, Adam
Jafree, Daniyal
Steele, Lloyd
MS, Vijaya Baskar
Haniffa, Muzlifah
Lotfollahi, Mohammad
author_facet Jeong, Dabin
Vahidi, Amirhossein
Ramírez-Suástegui, Ciro
Moullet, Marie
Ly, Kevin
Sanian, Mohammad Vali
Birk, Sebastian
Chang, Yinshui
Boxall, Adam
Jafree, Daniyal
Steele, Lloyd
MS, Vijaya Baskar
Haniffa, Muzlifah
Lotfollahi, Mohammad
contents Recent advances in computational pathology have leveraged vision-language models to learn joint representations of Hematoxylin and Eosin (HE) images with spatial transcriptomic (ST) profiles. However, existing approaches typically align HE tiles with their corresponding ST profiles at a single scale, overlooking fine-grained cellular structures and their spatial organization. To address this, we propose Sigmma, a multi-modal contrastive alignment framework for learning hierarchical representations of HE images and spatial transcriptome profiles across multiple scales. Sigmma introduces multi-scale contrastive alignment, ensuring that representations learned at different scales remain coherent across modalities. Furthermore, by representing cell interactions as a graph and integrating inter- and intra-subgraph relationships, our approach effectively captures cell-cell interactions, ranging from fine to coarse, within the tissue microenvironment. We demonstrate that Sigmm learns representations that better capture cross-modal correspondences, leading to an improvement of avg. 9.78\% in the gene-expression prediction task and avg. 26.93\% in the cross-modal retrieval task across datasets. We further show that it learns meaningful multi-tissue organization in downstream analyses.
format Preprint
id arxiv_https___arxiv_org_abs_2511_15464
institution arXiv
publishDate 2025
record_format arxiv
spellingShingle SIGMMA: Hierarchical Graph-Based Multi-Scale Multi-modal Contrastive Alignment of Histopathology Image and Spatial Transcriptome
Jeong, Dabin
Vahidi, Amirhossein
Ramírez-Suástegui, Ciro
Moullet, Marie
Ly, Kevin
Sanian, Mohammad Vali
Birk, Sebastian
Chang, Yinshui
Boxall, Adam
Jafree, Daniyal
Steele, Lloyd
MS, Vijaya Baskar
Haniffa, Muzlifah
Lotfollahi, Mohammad
Computer Vision and Pattern Recognition
Machine Learning
Recent advances in computational pathology have leveraged vision-language models to learn joint representations of Hematoxylin and Eosin (HE) images with spatial transcriptomic (ST) profiles. However, existing approaches typically align HE tiles with their corresponding ST profiles at a single scale, overlooking fine-grained cellular structures and their spatial organization. To address this, we propose Sigmma, a multi-modal contrastive alignment framework for learning hierarchical representations of HE images and spatial transcriptome profiles across multiple scales. Sigmma introduces multi-scale contrastive alignment, ensuring that representations learned at different scales remain coherent across modalities. Furthermore, by representing cell interactions as a graph and integrating inter- and intra-subgraph relationships, our approach effectively captures cell-cell interactions, ranging from fine to coarse, within the tissue microenvironment. We demonstrate that Sigmm learns representations that better capture cross-modal correspondences, leading to an improvement of avg. 9.78\% in the gene-expression prediction task and avg. 26.93\% in the cross-modal retrieval task across datasets. We further show that it learns meaningful multi-tissue organization in downstream analyses.
title SIGMMA: Hierarchical Graph-Based Multi-Scale Multi-modal Contrastive Alignment of Histopathology Image and Spatial Transcriptome
topic Computer Vision and Pattern Recognition
Machine Learning
url https://arxiv.org/abs/2511.15464