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Robust integration and annotation of single-cell and spatial omics data using interpretable gene programs.

Yuelei Zhang1, Wenxuan Ming1, Bianjiong Yu1

  • 1Nanjing Stomatology Hospital, Medical School and the State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210023, China.

Cell Genomics
|December 20, 2025
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Summary
This summary is machine-generated.

SSpMosaic decodes cellular complexity by identifying universal gene programs called metaprograms. This framework enables accurate cell type annotation and spatial mapping across diverse biological datasets and scales.

Keywords:
cell-type annotationcell-type deconvolutiondata integrationgene programinterpretabilitymetaprogramsomicssingle cellspatial domainspatial transcriptomics

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Area of Science:

  • Computational biology
  • Genomics
  • Spatial transcriptomics

Background:

  • Cellular identity is defined by complex, context-aware gene programs.
  • Integrating diverse biological data (e.g., single-nucleus, spatial transcriptomics) remains challenging.
  • Existing methods struggle with cross-dataset consistency and novel cell state discovery.

Purpose of the Study:

  • To introduce SSpMosaic, a computational framework for robust biological state representation.
  • To enable accurate cell type annotation and discovery of novel cell states.
  • To achieve resolution-agnostic spatial transcriptomics deconvolution and reference-free spatial characterization.

Main Methods:

  • Development of SSpMosaic, a framework utilizing metaprograms for cross-dataset alignment.
  • Application of metaprogram-based transfer learning for cell type annotation.
  • Integration of multi-modal data (single-nucleus, chromatin accessibility, spatial transcriptomics).
  • Resolution-agnostic deconvolution for spatial transcriptomics at various scales.

Main Results:

  • SSpMosaic enables consistent and accurate data integration across batches, modalities, and species.
  • The framework accurately annotates cell types and discovers novel cell states.
  • Achieved precise mapping of cell-type distributions from spot-level to subcellular scales.
  • Successfully resolved multi-stage spatial domain dynamics by integrating diverse data types.
  • Enabled reference-free spatial characterization and identification of conserved spatial ecotypes.

Conclusions:

  • SSpMosaic provides a universal framework for representing biological states using metaprograms.
  • The framework advances cell type annotation, spatial deconvolution, and discovery of cellular niches.
  • SSpMosaic facilitates a deeper understanding of spatial domain dynamics and cellular ecologies across biological samples.