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

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arXiv:2608.14924v1 Announce Type: cross 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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