# PaSTel: Anchoring Histology in Spatial Transcriptomics via Multi-Scale Hierarchical Bio-Prior Contrastive Pretraining

arXiv: https://arxiv.org/abs/2608.14924 · HTML: https://mlsanity.com/paper/2608.14924/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 10 of its 28 references that are in the map.
- First posted on arXiv 14 Aug 2026.

## Builds on (most cited first, 10 of 10)

- [Densely Connected Convolutional Networks](https://mlsanity.com/paper/1608.06993/) (2016)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Exemplar Guided Deep Neural Network for Spatial Transcriptomics Analysis of Gene Expression Prediction](https://mlsanity.com/paper/2210.16721/) (2022)
- [Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images](https://mlsanity.com/paper/2501.15598/) (2025)
- [Multimodal contrastive learning for spatial gene expression prediction using histology images](https://mlsanity.com/paper/2407.08216/) (2024)
- [ASIGN: An Anatomy-aware Spatial Imputation Graphic Network for 3D Spatial Transcriptomics](https://mlsanity.com/paper/2412.03026/) (2024)
- [Towards Unified Molecule-Enhanced Pathology Image Representation Learning via Integrating Spatial Transcriptomics](https://mlsanity.com/paper/2412.00651/) (2024)
- [High-Resolution Spatial Transcriptomics from Histology Images using HisToSGE](https://mlsanity.com/paper/2407.20518/) (2024)

## Abstract (arXiv)

Spatial transcriptomics (ST) links tissue morphology with molecular programs, motivating multimodal pretraining methods that align histology images with gene expression. However, existing approaches suffer from two key limitations: spatially informative gene selection is often dominated by ubiquitous housekeeping genes, leading to weakly discriminative representations, and independent spot-patch alignment fails to capture spatial dependencies that are critical for tissue organization. To address these challenges, we introduce PaSTel, a hierarchical multimodal pretraining framework that integrates biological priors at three levels. At the spot level, TF-IDF reweighting is used to identify spatially informative genes; at the functional level, curated KEGG pathways serve as anchors for encoding global biological semantics; and at the regional level, spatial clustering aggregates neighboring spots to model meso-scale tissue structure. Across multiple downstream tasks, PaSTel consistently outperforms existing vision and vision-omics encoders, demonstrating that incorporating multiscale biological priors yields more informative and transferable representations for spatial transcriptomics.