Summary: Spatial Transcriptomics is revolutionizing our ability to phenotypically characterize complex biological tissues and decipher cellular niches. With current technologies such as VisiumHD, thousands of genes can be detected across millions of spots (also called cells or bins depending on the technologies). Building upon the metacell concept, we present a workflow, called SuperSpot, to combine adjacent and transcriptomically similar spots into "metaspots". The process involves representing spots as nodes in a graph with edges connecting spots in spatial proximity and edge weights representing transcriptomic similarity. Hierarchical clustering is used to aggregate spots into metaspots at a user-defined resolution. We demonstrate that metaspots reduce the size and sparsity of spatial transcriptomic data and facilitate the analysis of large datasets generated with the most recent technologies.
Availability And Implementation: SuperSpot is an R package available at https://github.com/GfellerLab/SuperSpot and archived on Zenodo (https://doi.org/10.5281/zenodo.14222088). The code to reproduce the figures is available at https://github.com/GfellerLab/SuperSpot/tree/main/figures (https://doi.org/10.5281/zenodo.14222088).
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http://dx.doi.org/10.1093/bioinformatics/btae734 | DOI Listing |
Regen Ther
March 2025
Department of Periodontology, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo (Science Tokyo), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8510, Japan.
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January 2025
Institut de Neurociències, Department de Bioquímica i Biologia Molecular, Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
Alzheimer's disease (AD) is characterized by memory loss and neuropsychiatric symptoms associated with cerebral amyloid-β (Aβ) and tau pathologies, but whether and how these factors differentially disrupt neural circuits remains unclear. Here, we investigated the vulnerability of memory and emotional circuits to Aβ and tau pathologies in mice expressing mutant human amyloid precursor protein (APP), Tau or both APP/Tau in excitatory neurons. APP/Tau mice develop age- and sex-dependent Aβ and phosphorylated tau pathologies, the latter exacerbated at early stages, in vulnerable brain regions.
View Article and Find Full Text PDFSci Rep
January 2025
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.
Combining 3D cultures such as tumor spheroids and organoids with spatial omics holds great potential for tissue biology and cancer research. Yet, this potential is presently limited by technical and financial challenges of spatial omics methods and 3D cultures. To address this, we combine dye diffusion, the Smart-seq3xpress protocol for deep single-cell gene expression profiling, and dedicated probabilistic inference methods into diffusion Smart-seq3 (Smart-seq3D), to reveal the transcriptome of single cells along with their position along the core-periphery axis of spheroids.
View Article and Find Full Text PDFBrief Bioinform
November 2024
School of Artificial Intelligence, Jilin University, Qianjin Street 2699, 130010 Changchun, China.
Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.
View Article and Find Full Text PDFGlycoconj J
January 2025
Department of Radiology, First Affiliated Hospital of Guangxi Medical University, No.6 Shuangyong Road, Nanning, Guangxi, 530021, China.
In this study, spatial and single-cell transcriptome techniques were used to investigate the role of beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) in promoting peritoneal metastasis in ovarian cancer epithelial cells. We collected single-cell transcriptomic (GSE130000) and spatial transcriptomic datasets (GSE211956) from the Gene Expression Omnibus and RNA-sequencing data from The Cancer Genome Atlas. The Robust Cell Type Decomposition (RCTD) approach was implemented to integrate spatial and single-cell transcriptomic data.
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