ASHG Poster 2025

Abstract

Understanding tumor resistance requires insight into the epigenetic regulation that drives cell-state transitions and spatial heterogeneity within tissues. AtlasXomics’ spatial epigenomics platform enables high-resolution mapping of chromatin accessibility and histone modifications directly in tissue sections using spatial CUT&Tag and DBiT-seq chemistry. By profiling four key histone marks (H3K27ac, H3K36me2, H3K4me3, H3K27me3) across serial sections of gastric and prostate tumors, the study reveals distinct enhancer and promoter landscapes that correspond to tumor- and stroma-specific regulatory programs. Integrated spatial ATAC–H3K27ac analyses further identify group-specific enhancer activity, differential chromatin looping, and localized transcription factor networks underlying resistance phenotypes. Correlation with RNA Pol II and co-registered H&E images demonstrates that spatially restricted epigenetic activation aligns with pathological features and cell-type identities. Together, these data establish spatial epigenomics as a powerful framework for uncovering the regulatory logic of disease progression and guiding therapeutic discovery through multiomic integration of chromatin state and gene expression.