biostudies-literatureUnknownYang CMayo Clinic Center for Individualized MedicineNational Institutes of HealthNIGMS NIH HHSNational Science FoundationCoarsening Visium HD resolution from 8 to 64 <i>μ</i>m can flip cell-type co-localization from negative to positive ( r=-0.12→+0.80 ), yet investigators are routinely forced to coarsen because current deconvolution methods cannot scale to million-bin datasets. Here we introduce FlashDeconv, which combines leverage-score importance sampling with sparse spatial regularization to match top-tier Bayesian accuracy while processing 1.6 million bins in 153 seconds on a standard laptop. Systematic multi-resolution analysis of Visium HD mouse intestine reveals a tissue-specific <i>resolution horizon</i> (8-16 <b><i>μ</i></b> m)-the scale at which this sign inversion occurs-validated by Xenium ground truth. Below this horizon, FlashDeconv provides the first sequencing-based quantification of Tuft cebioRxiv : the preprint server for biology2025.12.22.696108https://www.ebi.ac.uk/biostudies/studies/S-EPMC12776147biostudies-literatureFlashDeconv enables atlas-scale, multi-resolution spatial deconvolution via structure-preserving sketching.PMC12776147DMS1830392R01GM144351DMS2113359DMS2113360DMS1811747R01 GM144351Chen JZhang XYang CfalseFlashDeconv enables atlas-scale, multi-resolution spatial deconvolution via structure-preserving sketching.Coarsening Visium HD resolution from 8 to 64 <i>μ</i>m can flip cell-type co-localization from negative to positive ( r=-0.12→+0.80 ), yet investigators are routinely forced to coarsen because current deconvolution methods cannot scale to million-bin datasets. Here we introduce FlashDeconv, which combines leverage-score importance sampling with sparse spatial regularization to match top-tier Bayesian accuracy while processing 1.6 million bins in 153 seconds on a standard laptop. Systematic multi-resolution analysis of Visium HD mouse intestine reveals a tissue-specific <i>resolution horizon</i> (8-16 <b><i>μ</i></b> m)-the scale at which this sign inversion occurs-validated by Xenium ground truth. Below this horizon, FlashDeconv provides the first sequencing-based quantification of Tuft ce2026-01-01T00:00:00Z2026 Feb2026-07-09T11:58:37.257Z2026-07-09T11:04:37.473ZS-EPMC127761474150939110.64898/2025.12.22.696108