AI-powered virtual tissues from spatial proteomics for clinical diagnostics and biomedical discovery

arXiv (Cornell University)

Abstract

Spatial proteomics technologies have transformed our understanding of complex tissue architecture in cancer but present unique challenges for computational analysis. Each study uses a different marker panel and protocol, and most methods are tailored to single cohorts, which limits knowledge transfer and robust biomarker discovery. Here we present Virtual Tissues (VirTues), a general-purpose foundation model for spatial proteomics that learns marker-aware, multi-scale representations of proteins, cells, niches and tissues directly from multiplex imaging data. From a single pretrained backbone, VirTues supports marker reconstruction, cell typing and niche annotation, spatial biomarker discovery, and patient stratification, including zero-shot annotation across heterogeneous panels and datasets. In triple-negative breast cancer, VirTues-derived biomarkers predict anti-PD-L1 chemo-immunotherapy response and stratify disease-free survival in an independent cohort, outperforming state-of-the-art biomarkers derived from the same datasets and current clinical stratification schemes.

Authors 7

1. Johann Wenckstern

   École Polytechnique Fédérale de Lausanne

   Affiliation as printed

   School of Computer and Communication Sciences , EPFL , Lausanne , Switzerland,

2. Eeshaan Jain

   École Polytechnique Fédérale de Lausanne

   Affiliation as printed

   School of Computer and Communication Sciences , EPFL , Lausanne , Switzerland,

3. Kiril Vasilev

   ETH Zurich

   Affiliation as printed

   Department of Computer Science , ETH , Zurich , Switzerland,

4. Matteo Pariset

   ETH Zurich

   Affiliation as printed

   Department of Computer Science , ETH , Zurich , Switzerland,

5. Andreas N. WICKI

   University of Zurich · University Hospital Zurich

   Affiliation as printed

   Department of Medical Oncology and Hematology , University Hospital Zurich , Zurich , Switzerland,

   University of Zurich , Faculty of Medicine , Zurich , Switzerland,

6. Gabriele Gut

   University of Zurich · University Hospital Zurich

   Affiliation as printed

   Department of Medical Oncology and Hematology , University Hospital Zurich , Zurich , Switzerland,

   University of Zurich , Faculty of Medicine , Zurich , Switzerland,

7. Charlotte Bunne

   Ludwig Cancer Research · Swiss Cancer Center Léman · École Polytechnique Fédérale de Lausanne

   Affiliation as printed

   School of Computer and Communication Sciences , EPFL , Lausanne , Switzerland,

   Swiss Institute for Experimental Cancer Research , School of Life Sciences , EPFL , Lausanne , Switzerland