Inferring histology-associated gene expression gradients in spatial transcriptomic studies
Spatially resolved transcriptomics has revolutionized RNA studies by aligning RNA abundance with tissue structure, enabling direct comparisons between histology and gene expression. Traditional approaches to identifying signature genes often involve preliminary data grouping, which can overlook subtle expression patterns in complex tissues. We present Spatial Gradient Screening, an algorithm which facilitates the supervised detection of histology-associated gene expression patterns without prior data grouping. Utilizing spatial transcriptomic data along with single-cell deconvolution from injured mouse cortex, and TCR-seq data from brain tumors, we compare our methodology to standard differential gene expression analysis. Our findings illustrate both the advantages and limitations of cluster-free detection of gene expression, offering more profound insights into the spatial architecture of transcriptomes. The algorithm is embedded in SPATA2, an open-source framework written in R, which provides a comprehensive set of tools for investigating gene expression within tissue.
Authors
- Jan Kueckelhaus
- Jasim Kada Benotmane (ORCID: https://orcid.org/0009-0005-2100-913X)
- Jovica Ninkovic (ORCID: https://orcid.org/0000-0002-4381-0041)
- Oliver Schnell (ORCID: https://orcid.org/0000-0002-1284-1427)
- Jürgen Beck (ORCID: https://orcid.org/0000-0002-7687-6098)
- Martin Dichgans (ORCID: https://orcid.org/0000-0002-0654-387X)
- Christina Koupourtidou (ORCID: https://orcid.org/0000-0002-8352-1498)
- Dieter Henrik Heiland (ORCID: https://orcid.org/0000-0002-9258-3033)
- Simon Frerich (ORCID: https://orcid.org/0000-0002-8275-6113)
Institutions
- University of Freiburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University Medical Center Freiburg (DE)
- German Center for Neurodegenerative Diseases (DE)
- LMU Klinikum (DE)
- Universitätsklinikum Erlangen (DE)
- Munich Cluster for Systems Neurology (DE)
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-08-23
- DOI
- https://doi.org/10.1038/s41467-024-50904-x
- Citations
- 62
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 14.50
Funders
- Deutsche Forschungsgemeinschaft
- Fondation Leducq
- Bundesministerium für Bildung und Forschung
- Deutschen Konsortium für Translationale Krebsforschung