1. Multiscale topology classifies cells in subcellular spatial transcriptomics.
- Author
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Benjamin K, Bhandari A, Kepple JD, Qi R, Shang Z, Xing Y, An Y, Zhang N, Hou Y, Crockford TL, McCallion O, Issa F, Hester J, Tillmann U, Harrington HA, and Bull KR
- Subjects
- Animals, Female, Humans, Mice, Disease Models, Animal, Fluorescent Antibody Technique, Lupus Nephritis genetics, Lupus Nephritis immunology, Lupus Nephritis metabolism, Lupus Nephritis pathology, Reproducibility of Results, Cells classification, Cells metabolism, Gene Expression Profiling methods, Kidney cytology, Kidney immunology, Kidney metabolism, Kidney pathology, Transcriptome, Intracellular Space genetics, Intracellular Space metabolism
- Abstract
Spatial transcriptomics measures in situ gene expression at millions of locations within a tissue
1 , hitherto with some trade-off between transcriptome depth, spatial resolution and sample size2 . Although integration of image-based segmentation has enabled impactful work in this context, it is limited by imaging quality and tissue heterogeneity. By contrast, recent array-based technologies offer the ability to measure the entire transcriptome at subcellular resolution across large samples3-6 . Presently, there exist no approaches for cell type identification that directly leverage this information to annotate individual cells. Here we propose a multiscale approach to automatically classify cell types at this subcellular level, using both transcriptomic information and spatial context. We showcase this on both targeted and whole-transcriptome spatial platforms, improving cell classification and morphology for human kidney tissue and pinpointing individual sparsely distributed renal mouse immune cells without reliance on image data. By integrating these predictions into a topological pipeline based on multiparameter persistent homology7-9 , we identify cell spatial relationships characteristic of a mouse model of lupus nephritis, which we validate experimentally by immunofluorescence. The proposed framework readily generalizes to new platforms, providing a comprehensive pipeline bridging different levels of biological organization from genes through to tissues., (© 2024. The Author(s).)- Published
- 2024
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