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Reconstructing single-cell resolution from spatial transcriptomics with CellRefiner
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DOI：10.1038/s41467-026-70090-2.png)
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Abstract
En 中文
Single-cell RNA sequencing technologies profile the transcriptome of individual cells but lack the spatial context necessary for dissecting cellular interactions like cell-cell communications. On the other hand, most current spatial transcriptomic technologies lack cellular resolution, limiting their capability for realistic downstream analysis. Here we present CellRefiner, a physical model-based method that integrates a single-cell dataset with a paired spatial dataset to generate single-cell resolution in the imputed spatial data. CellRefiner models cells as particles connected by forces, and then optimizes cell locations with spatial proximity constraints, gene expression similarity, and ligand-receptor interactions between cells. We systematically benchmark CellRefiner over a variety of simulated and real datasets using Visium, MERFISH, seqFISH, Slide-seqV2, and STARmap datasets to demonstrate its accuracy, robustness, and ability to recover spatial patterns of cells. We also demonstrate its utility for improving spatially dependent analysis over the original spatial data for the contact-based cell-cell communication on mouse cortex and lymph node tissues. Our results show CellRefiner is capable of reconstructing single-cell resolution from non-single-cell resolution spatial data, allowing downstream analysis that requires individual-cell resolution and spatial information. CellRefiner uses a biophysical, particle-based model to reconstruct realistic single-cell spatial maps from low-resolution spatial transcriptomics, enabling more accurate analysis of cell-cell communication and tissue organization than spot-level data alone.
Keywords:
Computational models
Data integration
Transcriptomics
Science
Humanities and Social Sciences
multidisciplinary
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