SEPIA: A Marker-Aware Foundation Model for Immunohistochemistry

SEPIA learns marker-aware representations of immunohistochemistry (IHC) images. It combines hematoxylin and DAB image representations with protein embeddings that encode the identity of the stained marker.

SEPIA is initialized from Hibou-L and trained with H/D inpainting. This repository contains the model weights.

Model weights

Model Architecture Embedding dimension Weights
SEPIA ViT-L/14 1024 sepia.pth

Model overview

SEPIA takes an RGB IHC tile and its marker identity as inputs. The standard tile size is 224×224 pixels. Images are separated into hematoxylin-only and DAB-only renderings, then normalized using the checkpoint's image statistics.

The two renderings share a patch projection and produce paired H/D tokens. A projected ESM protein embedding conditions the DAB tokens on the stained marker. The encoder produces a 1024-dimensional image representation and separate H and D patch representations.

Benchmarking

Test-set AUROC (%) reported as mean ± standard error over five repeats on seven IHC tasks, alongside the mean rank over all 44 IHC-relevant tasks. The pan-cancer DAB localization task uses 13 held-out markers. Best mean values are bold. Lower mean rank is better.

Model Breast cancer
Histological subtype
Breast cancer
Luminal vs non-luminal
DLBCL
HANS subtype
DLBCL
Double expressor
NSCLC
Intratumoral CD8
Type-2 diabetes
Diabetic status
Pan-cancer
DAB location (held out)
Overall
Mean rank ↓ (44 tasks)
DINOv2 54.9 ± 0.4 81.1 ± 0.7 73.2 ± 0.8 64.9 ± 1.5 71.0 ± 1.4 73.6 ± 0.8 77.4 ± 0.3 7.30 ± 0.19
ResNet-50 56.0 ± 0.7 86.3 ± 0.3 77.6 ± 0.6 76.6 ± 0.9 75.2 ± 0.2 72.2 ± 1.1 81.4 ± 0.8 6.64 ± 0.20
PathoDuet 50.9 ± 1.7 85.3 ± 0.5 82.8 ± 0.7 83.0 ± 0.9 77.7 ± 0.6 74.9 ± 0.8 88.2 ± 0.6 5.68 ± 0.25
StainNet 54.9 ± 1.6 88.4 ± 0.5 87.5 ± 0.9 90.2 ± 0.7 80.5 ± 0.5 79.6 ± 1.2 88.4 ± 0.7 3.70 ± 0.26
UNI 56.2 ± 1.9 87.2 ± 0.7 84.9 ± 0.8 85.2 ± 0.6 82.6 ± 0.4 76.1 ± 0.7 88.2 ± 0.4 3.50 ± 0.18
Hibou 57.0 ± 1.4 87.6 ± 0.4 86.7 ± 0.4 89.1 ± 0.8 82.3 ± 0.3 73.1 ± 0.7 91.1 ± 0.5 3.43 ± 0.24
UNI2-h 57.2 ± 0.5 87.2 ± 0.6 86.3 ± 0.8 81.2 ± 1.2 83.7 ± 0.3 74.0 ± 0.6 83.6 ± 0.8 3.09 ± 0.32
SEPIA 61.6 ± 1.7 89.4 ± 0.3 90.9 ± 0.4 91.9 ± 0.4 83.6 ± 0.2 89.3 ± 0.4 96.4 ± 0.4 2.66 ± 0.27

Acknowledgements

We thank the teams behind Hibou, DINOv2, and ESM for their publicly available models and implementations.

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