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A multimodal foundation model for joint analysis of histopathology and spatial proteomics data, enabling cross-modal virtual staining, cellular phenotyping, biomarker discovery and clinically relevant patient stratification across diverse tissues and imaging technologies.

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VirTues-M2 Logo

A multimodal foundation model for tissue proteomics and morphology in cancer

🤗 [Model Weights] | [Cite] | [Data]

VirTues-M2 is a foundation model for tissue biology that jointly learns from routine H&E histopathology and multiplex spatial proteomics within a single architecture. It follows an early-fusion design: pixel-aligned images are embedded by modality-specific tokenizers (an RGB tokenizer for H&E and a multiplex tokenizer for spatial proteomics) and processed by a shared vision transformer backbone. In the multiplex tokenizer, each channel is combined with a protein foundation model embedding of its marker identity. This lets VirTues-M2 handle arbitrary and varying marker panels and stay robust to missing modalities, incomplete pairing and imperfect alignment. VirTues-M2 is pretrained on the largest open-source multiplex spatial proteomics collection with partially paired H&E, covering 5,849 patients, 37 studies and 17,275 multiplex tissues acquired with PhenoCycler (CODEX), Orion, IMC and MIBI. The resulting joint representation can be used in tasks such as treatment response, tissue phenotyping, panoptic cell segmentation, virtual staining, biomarker discovery and adaptive marker panel selection.

VirTues-M2 Overview

Installation

To install all dependencies needed to run VirTues-M2, download the repository first:

git clone https://github.com/bunnelab/virtues-m2.git
cd virtues-m2

Then, create an environment and activate it:

conda create --name virtuesm2 python=3.11
conda activate virtuesm2

Afterwards, install all requirements:

pip install -e .

Inference

Marker embeddings

To encode the antibody markers of the spatial proteomics images, we use the ESM-2 protein language model to encode the corresponding proteins. Instructions for generating these embeddings can be found in the VirTues GitHub repository, here.

Model weights

The model weights for the VirTues-M2 backbone, segmentation and virtual staining head are all available on HuggingFace and currently reside in the v2 branch. The model backbone can be instantiated as follows:

from virtuesm2.models.virtuesm2_hf import VirTuesM2_HF
model = VirTuesM2_HF.from_pretrained("bunnelab/virtues-m2", marker_embedding_dir="example_data/esm_embeddings", force_download=True, revision="v2")

Tutorial Notebooks

We provide three inference notebooks in the notebooks folder to show how to embed multi- and uni-modal images with VirTues-M2 and potential downstream tasks that leverage the frozen VirTues-M2 encoding abilities. In the notebook 1_inference_PCAs.ipynb, simple PCAs are shown, whereas in 2_cell_segmentation.ipynb we demonstrate panoptic cell segmentation based on VirTues-M2 for joint cell phenotyping and cell instance segmentation in a single forward pass. The notebook 3_virtual_staining.ipynb demonstrates how to perform virtual staining on a subset of 11 markers.

If you want to apply VirTues-M2 on the harmonized datasets provided within the spora spatial proteomics dataset collection, we provide additional notebooks for cell segmentation and virtual staining showcasing the integration of spora into VirTues-M2 based processing pipelines.

Models

Model Name Training Data License of Model Weights HuggingFace Branch Segmentation Head Virtual Staining Head
virtues-m2-sp37 37 partially multimodal spatial proteomics datasets (see spora) CC BY-NC 4.0 v2 ✔ ✔

License and Terms of Use

Copyright (c) ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE, Switzerland, Laboratory of Artificial Intelligence in Molecular Medicine, 2026

This repository and related code are released under the MIT License. See LICENSE.md for details.

Reference

If you find our work useful in your research or if you use parts of this code please consider citing our paper:

@article{...,
  title = {},
  author = {},
  journal = {},
  publisher = {},
  year = {}
}

About

A multimodal foundation model for joint analysis of histopathology and spatial proteomics data, enabling cross-modal virtual staining, cellular phenotyping, biomarker discovery and clinically relevant patient stratification across diverse tissues and imaging technologies.

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