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Updated: Feb 5, 2026

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Self-supervised pretraining with NuSPIRe unlocks nuclear morphology-driven insights in spatial omics.

Yuwei Hua1, Shiyu Li1, Yong Zhang2

  • 1State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Institute for Regenerative Medicine, Department of Neurosurgery, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Shanghai East Hospital, Tongji University, 1239 Siping Road, Shanghai, 200092, China.

Genome Biology
|February 3, 2026
PubMed
Summary

NuSPIRe, a deep learning model, analyzes nuclear morphology from DAPI images for cell identification and gene expression insights. This AI tool optimizes experiments in spatial omics and cell biology.

Keywords:
Nuclear morphologyRepresentation learningSelf-supervised pretrainingSpatial transcriptomics

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Area of Science:

  • Cell Biology
  • Bioinformatics
  • Artificial Intelligence

Background:

  • Nuclear morphology provides critical phenotypic information for understanding cellular states.
  • The full potential of nuclear morphology analysis remains largely untapped in biomedical research.
  • Existing methods often require extensive annotations for accurate analysis.

Purpose of the Study:

  • To introduce NuSPIRe, a self-supervised deep learning model for nuclear morphology analysis.
  • To demonstrate NuSPIRe's capabilities in cell type identification and perturbation detection.
  • To explore the integration of nuclear morphology with spatial omics data for novel biological insights.

Main Methods:

  • Developed NuSPIRe, a self-supervised deep learning model utilizing DAPI-stained nuclear images.
  • Pretrained NuSPIRe on a large dataset of 15.52 million cell nucleus images.
  • Integrated NuSPIRe with spatial omics data to correlate nuclear structure with gene expression.

Main Results:

  • NuSPIRe achieved robust performance in cell type identification and perturbation detection, even with limited annotations.
  • Significant correlations were uncovered between nuclear morphology features and gene expression patterns.
  • NuSPIRe demonstrated effectiveness in AI-driven experimental optimization for spatial omics.

Conclusions:

  • Self-supervised learning with NuSPIRe effectively leverages nuclear morphology for biomedical analysis.
  • NuSPIRe enhances data efficiency and discovery in spatial omics and molecular cell biology.
  • Nuclear morphology analysis using AI offers a powerful approach to understanding cellular phenotypes and gene regulation.