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Comprehensive Spatial Profiling of Species-agnostic Transcriptomes via Stereo-seq
Published on: October 31, 2025
Inference of spatial chromatin accessibility via integration of spatial transcriptomics and single-cell multi-omics
1Center for Computational Biology and Bioinformatics, Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Nature Communications
|June 4, 2026
Summary
This study introduces ISON, a computational method that integrates spatial transcriptomics with single-cell multi-omics data. ISON predicts chromatin accessibility and reconstructs spatial gene regulatory networks, advancing our understanding of gene regulation in tissues.
Area of Science:
- Genomics
- Systems Biology
- Computational Biology
Background:
- Spatial transcriptomics and single-cell multi-omics offer powerful insights into gene regulation.
- Simultaneous spatial multi-omics profiling kits are currently unavailable, limiting data generation.
Purpose of the Study:
- To present ISON, a unified computational method for integrative spatial multi-omics analysis.
- To enable accurate prediction of chromatin accessibility profiles for spatial spots.
- To reconstruct spatially resolved gene regulatory networks.
Main Methods:
- Development of ISON, a computational method for integrating single-cell multiome and spatial transcriptomics data.
- Scalable analysis in terms of time and memory.
- Prediction of chromatin accessibility and estimation of transcription factor activity at the spot level.
Main Results:
- ISON accurately predicts chromatin accessibility profiles for spatial spots.
- Reconstruction of spatially resolved gene regulatory networks.
- Estimation of transcription factor activity, distinguishing between TFs within the same family.
- Application to Alzheimer's disease data revealed disease- and age-specific spatially variable gene regulatory modules.
Conclusions:
- ISON is a scalable and effective computational method for integrative spatial multi-omics analysis.
- ISON enables the estimation of transcription factor activity at the spot level, offering unique insights.
- The method has potential for uncovering spatially organized mechanisms in complex biological processes, such as Alzheimer's disease.
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