FlashDeconv reveals resolution horizons in atlas-scale spatial transcriptomics

Coarsening Visium HD resolution from 8 to 64 μm can flip cell-type colocalization from negative to positive $(r=-0.12\to +0.80)$ , yet many widely used compositional deconvolution workflows require coarsening or subsampling at million-bin scale. Here we introduce FlashDeconv, which combines leverage-score importance sampling with sparse spatial regularization to achieve competitive benchmark accuracy while processing 1.6 million bins in 153 seconds on commodity hardware. Systematic multi-resolution analysis of Visium HD mouse intestine reveals a tissue-specific resolution horizon (8-16 μ m)-the scale at which this sign inversion occurs-validated by Xenium ground truth. Below this horizon, FlashDeconv provides, to our knowledge, the first sequencing-based quantification of Tuft cell chemosensory niches (15.3-fold stem cell enrichment). In a 1.6-million-bin human colorectal cancer cohort, FlashDeconv uncovers neutrophil inflammatory microdomains co-localized with immunoregulatory dendritic cells (mRegDC) at the tumor-stroma interface-spatial niches largely missed by discrete-label summaries, with RCTD doublet mode labeling only 2.3% of hotspot bins as neutrophil singlets.