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arXiv · 2506.21857

SPADE: Spatial Transcriptomics and Pathology Alignment Using a Mixture of Data Experts for an Expressive Latent Space

Ekaterina Redekop·Mara Pleasure·Zichen Wang·Kimberly Flores·Anthony Sisk·William Speier·Corey W. Arnold
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Abstract

The rapid growth of digital pathology and advances in self-supervised deep learning have enabled the development of foundational models for various pathology tasks across diverse diseases. While multimodal approaches integrating diverse data sources have emerged, a critical gap remains in the comprehensive integration of whole-slide images (WSIs) with spatial transcriptomics (ST), which is crucial for capturing critical molecular heterogeneity beyond standard hematoxylin & eosin (H&E) staining. We introduce SPADE, a foundation model that integrates histopathology with ST data to guide image representation learning within a unified framework, in effect creating an ST-informed latent space. SPADE leverages a mixture-of-data experts technique, where experts are created via two-stage imaging feature-space clustering using contrastive learning to learn representations of co-registered WSI patches and gene expression profiles. Pre-trained on the comprehensive HEST-1k dataset, SPADE is evaluated on 20 downstream tasks, demonstrating significantly superior few-shot performance compared to baseline models, highlighting the benefits of integrating morphological and molecular information into one latent space. Code and pretrained weights are available at https://github.com/uclabair/SPADE.

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Ekaterina Redekop, Mara Pleasure, Zichen Wang, Kimberly Flores, Anthony Sisk, William Speier, Corey W. Arnold. 2025-06-27. SPADE: Spatial Transcriptomics and Pathology Alignment Using a Mixture of Data Experts for an Expressive Latent Space. https://arxiv.org/abs/2506.21857

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