Dynamic Activity in cis-Regulatory Elements of Leukocytes Identifies Transcription Factor Activation and Stratifies COVID-19 Severity in ICU Patients
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE221067 | GEO | 2023/03/02
REPOSITORIES: GEO
Similar Datasets
Project description:The transcription factors programs mediating the immune response to COVID-19 and disease outcomes are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped-small (cs)RNA-seq, in contrast to capturing the steady-state transcripts by conventional RNA-seq, allows unbiased identification of the underlying transcription factors activity and regulatory pathways. Here, we profile the acute changes in transcription initiation in peripheral leukocytes from critically ill COVID-19 patients, thereby identifying transcription factor (TF) motifs that track the severity of COVID19-associated lung injury, disease resolution, and outcome. Unbiased clustering reveals distinct subsets of cis-regulatory elements that delineate the regulation of specific pathways, cell types, and the combinatorial activity of transcription factors. We find evidence of critical roles for regulatory networks driven by signal-dependent and lineage determining transcription factors, showing that STAT/BCL6 and E2F/MYB regulatory programs from myeloid cell populations are activated in patients with poor disease outcomes and associated with single nucleotide genetic variants implicated in COVID-19 susceptibility. More broadly, we demonstrate how capturing acute, disease-mediated changes in transcription initiation can provide insight into the underlying molecular mechanisms and stratify patient disease severity.
2023-03-02 | GSE221065 | GEO
Project description:The transcription factors programs mediating the immune response to COVID-19 and disease outcomes are not fully understood. Capturing active transcription initiation from cis-regulatory elements such as enhancers and promoters by capped-small (cs)RNA-seq, in contrast to capturing the steady-state transcripts by conventional RNA-seq, allows unbiased identification of the underlying transcription factors activity and regulatory pathways. Here, we profile the acute changes in transcription initiation in peripheral leukocytes from critically ill COVID-19 patients, thereby identifying transcription factor (TF) motifs that track the severity of COVID19-associated lung injury, disease resolution, and outcome. Unbiased clustering reveals distinct subsets of cis-regulatory elements that delineate the regulation of specific pathways, cell types, and the combinatorial activity of transcription factors. We find evidence of critical roles for regulatory networks driven by signal-dependent and lineage determining transcription factors, showing that STAT/BCL6 and E2F/MYB regulatory programs from myeloid cell populations are activated in patients with poor disease outcomes and associated with single nucleotide genetic variants implicated in COVID-19 susceptibility. More broadly, we demonstrate how capturing acute, disease-mediated changes in transcription initiation can provide insight into the underlying molecular mechanisms and stratify patient disease severity.
2023-03-02 | GSE221066 | GEO
Project description: Not available
| S-EPMC8404884 | biostudies-literature
Project description:The causative organism, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibits a wide spectrum of clinical manifestations in disease-ridden patients. Differences in the severity of COVID-19 ranges from asymptomatic infections and mild cases to the severe form, leading to acute respiratory distress syndrome (ARDS) and multiorgan failure with poor survival. MiRNAs can regulate various cellular processes, including proliferation, apoptosis, and differentiation, by binding to the 3′UTR of target mRNAs inducing their degradation, thus serving a fundamental role in post-transcriptional repression. Alterations of miRNA levels in the blood have been described in multiple inflammatory and infectious diseases, including SARS-related coronaviruses. We used microarrays to delineate the miRNAs and snoRNAs signature in the peripheral blood of severe COVID-19 cases (n=9), as compared to mild (n=10) and asymptomatic (n=10) patients, and identified differentially expressed transcripts in severe versus asymptomatic, and others in severe versus mild COVID-19 cases. A cohort of 29 male age-matched patients were selected. All patients were previously diagnosed with COVID-19 using TaqPath COVID-19 Combo Kit (Thermo Fisher Scientific, Waltham, Massachusetts), or Cobas SARS-CoV-2 Test (Roche Diagnostics, Rotkreuz, Switzerland), with a CT value < 30. Additional criterion for selection was age between 35 and 75 years. Participants were grouped into severe, mild and asymptomatic. Classifying severe cases was based on requirement of high-flow oxygen support and ICU admission (n=9). Whereas mild patients were identified based on symptoms and positive radiographic findings with pulmonary involvement (n=10). Patients with no clinical presentation were labelled as asymptomatic cases (n=10).
2022-03-01 | E-MTAB-10970 | biostudies-arrayexpress
Project description: Not available
| S-EPMC7276819 | biostudies-literature
Project description: Not available
| S-EPMC8370055 | biostudies-literature
Project description:We investigated the effect of IL-13 neutralization on COVID-19 disease progression in mice.
2021-07-23 | GSE180557 | GEO
Project description:Matched samples from individuals before they contracted COVID-19 and after they were diagnosed with it were used for TMT-based relative quantitation of their plasma proteome and glycoproteome to study the effects of this infectious disease. Twenty one COVID-19 patients whose pre-COVID-19 plasma samples were also available were selected for this study. These patients had varied courses of illness and were classified based on WHO guidelines into outpatients and those with severe and critical illness. 21 matched sample pairs were divided into 3 sets for 3 TMTPro 16-plex-based mass spectrometry experiments with 8 (set01), 8 (set02), and 5 (set03) patients each. Plasma-derived tryptic peptides from each sample were TMT-labeled, and each pooled set was used for separate experiments for total proteomics and glycoproteomics. A pooled aliquot from each set was used to enrich glycopeptides by size exclusion chromatography and another aliquot was used to fractionate all peptides by basic pH reversed phase liquid chromatography. Enriched glycopeptides were analyzed by LC-MS/MS and quantified across samples using TMT reporter ion intensities. Fold changes (intensity of protein or glycopeptide from a patient with COVID-19/that from the same patient before they had COVID-19) for each protein and glycopeptide were calculated for all patients to assess changes in the proteome that may be attributable to this illness. We detected 1,520 proteins, of which 472 were detected in all patients. 3,892 glycopeptides were identified at 1% FDR at peptide, glycan and glycopeptides levels and their reporter ion intensities were quantified. 732 glycopeptides from 232 glycoproteins were detected in all patients.
2022-08-12 | PXD029376 | Pride
Project description:Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA-Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups.
2022-07-19 | E-MTAB-10926 | biostudies-arrayexpress
Project description:Genome-wide DNA methylation analysis of COVID-19 severity using the Illumina HumanMethylationEPIC microarray platform to analyze over 850,000 methylation sites, comparing COVID-19 patients with patients presenting with respiratory symptoms, but negative for COVID-19, using whole blood tissue.
2021-05-31 | GSE174818 | GEO