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Ouologuem, S. ; Martens, L.D. ; Schaar, A. ; Shulman, M. ; Gagneur, J. ; Theis, F.J.

Spatial transcriptomics deconvolution methods generalize well to spatial chromatin accessibility data.

Bioinformatics 41, i314-i322 (2025)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
MOTIVATION: Spatially resolved chromatin accessibility profiling offers the potential to investigate gene regulatory processes within the spatial context of tissues. However, current methods typically work at spot resolution, aggregating measurements from multiple cells, thereby obscuring cell-type-specific spatial patterns of accessibility. Spot deconvolution methods have been developed and extensively benchmarked for spatial transcriptomics, yet no dedicated methods exist for spatial chromatin accessibility, and it is unclear if RNA-based approaches are applicable to that modality. RESULTS: Here, we demonstrate that these RNA-based approaches can be applied to spot-based chromatin accessibility data by a systematic evaluation of five top-performing spatial transcriptomics deconvolution methods. To assess performance, we developed a simulation framework that generates both transcriptomic and accessibility spot data from dissociated single-cell and targeted multiomic datasets, enabling direct comparisons across both data modalities. Our results show that Cell2location and RCTD, in contrast to other methods, exhibit robust performance on spatial chromatin accessibility data, achieving accuracy comparable to RNA-based deconvolution. Generally, we observed that RNA-based deconvolution exhibited slightly better performance compared to chromatin accessibility-based deconvolution, especially for resolving rare cell types, indicating room for future development of specialized methods. In conclusion, our findings demonstrate that existing deconvolution methods can be readily applied to chromatin accessibility-based spatial data. Our work provides a simulation framework and establishes a performance baseline to guide the development and evaluation of methods optimized for spatial epigenomics. AVAILABILITY AND IMPLEMENTATION: All methods, simulation frameworks, peak selection strategies, analysis notebooks and scripts are available at https://github.com/theislab/deconvATAC.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1367-4803
e-ISSN 1367-4811
Journal Bioinformatics
Quellenangaben Volume: 41, Issue: Supplement_1, Pages: i314-i322 Article Number: , Supplement: ,
Publisher Oxford University Press
Publishing Place Oxford
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants German Network for Bioinformatics Infrastructure
NBI
European Research Council
Deutsche Forschungsgemeinschaft
Munich School for Data Science
Helmholtz Association