ArticleGenome research2023
Genetic control of the dynamic transcriptional response to immune stimuli and glucocorticoids at single-cell resolution.
Article in Genome research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 16 citations in OpenAlex.
- Post-genome-wide association study variant-to-function challenges in asthma research.The Journal of allergy and clinical immunology · 2026Review
- Decoding Immune Regulation: From Genetic Variation to Mechanism Through Single-Cell Genomics.Immune network · 2026Review
- Evidence for genetically-based sperm discrimination in the vaginal tract of a primate species.PLoS biology · 2026Article
- Article
- Probabilistic classification of gene-by-treatment interactions on molecular count phenotypes.PLoS genetics · 2025Article
- Functional characterization of eQTLs and asthma risk loci with scATAC-seq across immune cell types and contexts.American journal of human genetics · 2025Article
- scTWAS Atlas: an integrative knowledgebase of single-cell transcriptome-wide association studies.Nucleic acids research · 2025Article
- Perinatal glucocorticoid sensitivity in the preterm newborn: molecular mechanisms, endogenous determinants, and clinical implications.Frontiers in endocrinology · 2025Review
- Genotype × environment interactions in gene regulation and complex traits.Nature genetics · 2024Review
- The Effect of Physical Activity and Repeated Whole-Body Cryotherapy on the Expression of Modulators of the Inflammatory Response in Mononuclear Blood Cells among Young Men.Journal of clinical medicine · 2024Article
- Cell-type-specific and disease-associated expression quantitative trait loci in the human lung.Nature genetics · 2024Article
- SingleQ: a comprehensive database of single-cell expression quantitative trait loci (sc-eQTLs) cross human tissues.Database : the journal of biological databases and curation · 2024Article
- Single-cell genomics meets human genetics.Nature reviews. Genetics · 2023Review
- A robust model for cell type-specific interindividual variation in single-cell RNA sequencing data.bioRxiv : the preprint server for biology · 2023Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Synthetic glucocorticoids, such as dexamethasone, have been used as a treatment for many immune conditions, such as asthma and, more recently, severe COVID-19. Single-cell data can capture more fine-grained details on transcriptional variability and dynamics to gain a better understanding of the molecular underpinnings of inter-individual variation in drug response. Here, we used single-cell RNA-seq to study the dynamics of the transcriptional response to glucocorticoids in activated peripheral blood mononuclear cells from 96 African American children. We used novel statistical approaches to calculate a mean-independent measure of gene expression variability and a measure of transcriptional response pseudotime. Using these approaches, we showed that glucocorticoids reverse the effects of immune stimulation on both gene expression mean and variability. Our novel measure of gene expression response dynamics, based on the diagonal linear discriminant analysis, separated individual cells by response status on the basis of their transcriptional profiles and allowed us to identify different dynamic patterns of gene expression along the response pseudotime. We identified genetic variants regulating gene expression mean and variability, including treatment-specific effects, and showed widespread genetic regulation of the transcriptional dynamics of the gene expression response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.