A deep learning-based multiscale integration of spatial omics with tumor morphology
Spatial Transcriptomics (spTx) offers unprecedented insights into the spatial arrangement of the tumor microenvironment, tumor initiation/progression and identification of new therapeutic target candidates. However, spTx remains unlikely to be routinely used in the near future. Hematoxylin and eosin (H&E) stained histological slides, on the other hand, are routinely generated for a large fraction of cancer patients. Here, we present a deep learning-based approach for multiscale integration of spTx with tumor morphology (MISO). We train MISO to predict spTx from H&E and validate it on a dataset of 72 10X Genomics Visium samples. We further validate our approach on 348 samples from five indications from the MOSAIC consortium and show that MISO significantly outperforms competing methods in extensive benchmarks. We demonstrate that MISO enables near single-cell-resolution, spatially-resolved gene expression prediction.
Authors
- Benoît Schmauch (ORCID: https://orcid.org/0000-0002-9478-6395)
- Julien Taı̈eb (ORCID: https://orcid.org/0000-0002-9955-4753)
- Elodie Pronier
- Eric Y. Durand (ORCID: https://orcid.org/0009-0004-9523-2900)
- Valentina Di Proietto (ORCID: https://orcid.org/0000-0003-1237-1506)
- Thomas Duboudin
- Jean-Baptiste Schiratti (ORCID: https://orcid.org/0000-0002-8797-1146)
- Loïc Herpin (ORCID: https://orcid.org/0000-0002-5535-0601)
- Delphine Le Corre
- Jean‐François Emile (ORCID: https://orcid.org/0000-0002-6073-4466)
- Rémy Dubois
- Antoine Olivier (ORCID: https://orcid.org/0000-0001-5119-9054)
- Wolf H. Fridman (ORCID: https://orcid.org/0000-0002-1332-0973)
- Alexandre Filiot (ORCID: https://orcid.org/0000-0001-7860-2245)
- Pierre Laurent‐Puig (ORCID: https://orcid.org/0000-0001-8475-5459)
- Lucie Gillet
- A Bourgoin
Institutions
- Inserm (FR)
- Université de Versailles Saint-Quentin-en-Yvelines (FR)
- Université Paris Cité (FR)
- Université Paris-Saclay (FR)
- Sorbonne Université (FR)
- Université Sorbonne Paris Nord (FR)
- Centre de Recherche des Cordeliers (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Ambroise-Paré (FR)
- Owl Research Institute (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1038/s41467-025-66691-y
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- University of Pittsburgh
- Centre Hospitalier Universitaire Vaudois
- Institut Gustave-Roussy
- Universitätsklinikum Erlangen