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SpaDiff: Denoising for Sequence-based Spatial Transcriptomics via Diffusion Process.

Jiazhang Cai1, Yongkai Chen2, Luyang Fang1

  • 1Department of Statistics, University of Georgia, 310 Herty Drive, Athens, 30602, GA, United States.

Biorxiv : the Preprint Server for Biology
|November 24, 2025
PubMed
Summary
This summary is machine-generated.

We developed SpaDiff, a new method to fix spot-swapping in spatial transcriptomics. This diffusion-based approach improves gene expression data accuracy and spatial analysis for better biological insights.

Keywords:
Data DenoisingDiffusion ModelScore FunctionSequence-based Spatial Transcriptomics

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Area of Science:

  • Molecular Biology
  • Genomics
  • Bioinformatics

Background:

  • Spatial transcriptomics offers gene expression analysis with spatial resolution.
  • Spot-swapping, or RNA molecule drift, introduces noise and reduces spatial specificity in this data.
  • Accurate spatial information is crucial for understanding tissue architecture and cellular interactions.

Purpose of the Study:

  • To introduce SpaDiff, a novel denoising method for spatial transcriptomics data.
  • To address the challenge of spot-swapping and its impact on data integrity.
  • To improve the accuracy of downstream spatial analysis.

Main Methods:

  • SpaDiff models spot-swapping as a diffusion process.
  • The method simulates RNA molecule displacement and reverses it to restore original positions.
  • Molecular counts are preserved throughout the denoising process.

Main Results:

  • SpaDiff effectively enhances the spatial specificity of gene expression.
  • The method improves overall data integrity by reducing noise from spot-swapping.
  • Evaluations on simulated and real data confirm SpaDiff's efficacy.

Conclusions:

  • SpaDiff is a powerful tool for correcting spot-swapping in spatial transcriptomics.
  • The enhanced data quality supports more accurate downstream analyses, including clustering and spatial domain identification.
  • This method advances the reliable application of spatial transcriptomics in biological research.