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bioRxiv · 10.64898/2025.12.22.696108

FlashDeconv enables atlas-scale, multi-resolution spatial deconvolution via structure-preserving sketching

Yang, C.·Chen, J.·Zhang, X.
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Abstract

Coarsening Visium HD resolution from 8 to 64 m can flip cell-type co-localization from negative to positive (r = -0.12 [->] +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 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.

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Yang, C., Chen, J., Zhang, X.. 2025-12-25. FlashDeconv enables atlas-scale, multi-resolution spatial deconvolution via structure-preserving sketching. https://doi.org/10.64898/2025.12.22.696108

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