MIST: Multi-Scale Spatial Context for Gene Expression Prediction from Histology

MIST is a Multi‑context Spatial Transformer that predicts spatial gene expression from H&E images by adding two context pathways to a standard Transformer: a coordinate‑invariant local pathway that attends to spatial k‑nearest‑neighbor spots, and a slide pathway that broadcasts a whole‑slide summary to every spot. In intra‑cohort evaluation across six human organ cohorts, MIST improves mean Pearson correlation by 9.7%–11.6% over the strongest baseline for 10‑, 50‑, and 100‑gene panels, and achieves lower MSE and MAE. It also outperforms baselines in leave‑one‑organ‑out transfer, domain recovery, and reproduces spatial expression patterns of cancer‑marker genes.

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