Region-aware bridge modeling enables interpretable mesoscale representation of spatial transcriptomic tissue sections

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ID: 318497
2026
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Abstract
Abstract Motivation Spatial transcriptomics maps tissue architecture at high resolution, but spot-level maps are difficult to compare across sections, whereas whole-section averages obscure regional organization. We developed region-aware bridge modeling to aggregate interpretable biological program features into compact mesoscale summaries. Results Using public colorectal cancer and breast cancer 10x Genomics high-definition Visium sections, we constructed epithelial-like, fibroblast, smooth or myoepithelial, and extracellular matrix bridge features from cell-state indicators, curated gene-program scores, and quality-control summaries. Median-quadrant aggregation produced an eight-region design matrix. Within-section validation showed non-random mesoscale heterogeneity: region-label shuffling reduced the overall mean absolute pairwise regional difference from 0.298 to 0.0020 in colorectal cancer and from 0.328 to 0.0024 in breast cancer, with empirical upper-tail probability values of 0.0002 for both analyses across 5000 permutations. Shifted and rotated partitions changed the overall heterogeneity metric by less than 10%. Exploratory ridge modeling identified fibroblast as the only non-target predictor in the extracellular matrix model, and Bayesian sensitivity analysis supported a positive fibroblast-extracellular matrix association. Supplementary lung, prostate, and ovarian cancer sections supported workflow applicability. Availability and implementation Code and processed outputs are available through GitHub and Zenodo under 10.5281/zenodo.19801620.
Reference Key
openalex_W7165630214 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Seung-Hwan Kim
Journal Bioinformatics advances
Year 2026
DOI
10.1093/bioadv/vbag176
URL
https://doi.org/10.1093/bioadv/vbag176
Keywords Keywords not found

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