PaSTel: Anchoring Histology in Spatial Transcriptomics via Multi-Scale Hierarchical Bio-Prior Contrastive Pretraining
- URL: http://arxiv.org/abs/2608.14924v1
- Date: Fri, 14 Aug 2026 22:26:17 GMT
- Title: PaSTel: Anchoring Histology in Spatial Transcriptomics via Multi-Scale Hierarchical Bio-Prior Contrastive Pretraining
- Abstract summary: PaSTel is a hierarchical multimodal pretraining framework that integrates biological priors at three levels.<n>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.<n>At the regional level, spatial clustering aggregates neighboring spots to model meso-scale tissue structure.
- Score: 4.434048652551508
- License: http://creativecommons.org/licenses/by/4.0/
- Abstract: 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.
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