Inferring histology-associated gene expression gradients in spatial transcriptomic studies

• Published in: Nature communications Vol. 15; no. 1; pp. 7280 - 19
• Main Authors: Kueckelhaus, Jan, Frerich, Simon, Kada-Benotmane, Jasim, Koupourtidou, Christina, Ninkovic, Jovica, Dichgans, Martin, Beck, Juergen, Schnell, Oliver, Heiland, Dieter Henrik
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 23.08.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 49; 631/114/2397; 631/114/2415; 631/114/794; Algorithms; Animals; Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; Gene expression; Gene Expression Profiling - methods; Histology; Humanities and Social Sciences; Humans; Injury analysis; Injury prevention; Mice; multidisciplinary; Ribonucleic acid; RNA; Science; Science (multidisciplinary); Screening; Single-Cell Analysis - methods; Spatial data; Transcriptome; Transcriptomes; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50904-x

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. Traditional approaches in spatial transcriptomics often rely on preliminary data grouping, which can overlook subtle expression patterns in tissues. Here, the authors present Spatial Gradient Screening, a tool which facilitates the detection of histology-associated gene expression patterns without prior data grouping.