The binding of transcription factors at proximal promoters and distal enhancers is central to gene regulation. Identifying regulatory motifs and quantifying their impact on expression remains challenging. Using a convolutional neural network trained on single-cell data, we infer putative regulatory motifs and cell type-specific importance. Our model, scover, explains 29% of the variance in gene expression in multiple mouse tissues. Applying scover to distal enhancers identified using scATAC-seq from the developing human brain, we identify cell type-specific motif activities in distal enhancers. Scover can identify regulatory motifs and their importance from single-cell data where all parameters and outputs are easily interpretable.
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http://dx.doi.org/10.1186/s13059-023-03021-9 | DOI Listing |
PLoS Comput Biol
January 2025
Department of Biomedical Informatics, University of Colorado Anschutz School of Medicine, Aurora, Colorado, United States of America.
While single-cell experiments provide deep cellular resolution within a single sample, some single-cell experiments are inherently more challenging than bulk experiments due to dissociation difficulties, cost, or limited tissue availability. This creates a situation where we have deep cellular profiles of one sample or condition, and bulk profiles across multiple samples and conditions. To bridge this gap, we propose BuDDI (BUlk Deconvolution with Domain Invariance).
View Article and Find Full Text PDFCell Rep
January 2025
Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z3, Canada; Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address:
Here, we used single cell RNA sequencing and single cell spatial transcriptomics to characterize the forebrain neural stem cell (NSC) niche under homeostatic and injury conditions. We defined the dorsal and lateral ventricular-subventricular zones (V-SVZs) as two distinct neighborhoods and showed that, after white matter injury, NSCs are activated to make oligodendrocytes dorsally for remyelination. This activation is coincident with an increase in transcriptionally distinct microglia in the dorsal V-SVZ niche.
View Article and Find Full Text PDFAfr J Lab Med
December 2024
College of Medicine, University of Ibadan, Ibadan, Nigeria.
J Clin Hypertens (Greenwich)
January 2025
Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Evidence suggests that approximately 63.0%-84.2% of stroke survivors have hypertension, yet there is currently no stroke prediction tool specifically designed for individuals with hypertension.
View Article and Find Full Text PDFSci China Life Sci
January 2025
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, 100191, China.
Adipogenesis is the healthy expansion of white adipose tissue (WAT), serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the body. Therefore, the identification of novel regulatory molecules in adipogenesis, specifically membrane receptors such as G protein-coupled receptors (GPCRs), holds significant clinical promise. These receptors can serve as viable targets for pharmaceuticals, offering potential for restoring metabolic homeostasis in individuals with obesity.
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