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| Status |
Public on Mar 02, 2023 |
| Title |
Dynamic Activity in cis-Regulatory Elements of Leukocytes Identifies Transcription Factor Activation and Stratifies COVID-19 Severity in ICU Patients [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
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| Overall design |
Comparison of transcriptional activity over time among COVID-19 patients with varying disease severity. Total RNA was obtained from whole blood samples.
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| Contributor(s) |
Lam M, Duttke SH, Benner CW, Coufal NG |
| Citation(s) |
36758547 |
| |
| Submission date |
Dec 15, 2022 |
| Last update date |
Jun 05, 2023 |
| Contact name |
Max Chang |
| E-mail(s) |
mchang@ucsd.edu
|
| Organization name |
University of California, San Diego
|
| Street address |
9500 Gilman Drive
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (55)
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| This SubSeries is part of SuperSeries: |
| GSE221067 |
Dynamic Activity in cis-Regulatory Elements of Leukocytes Identifies Transcription Factor Activation and Stratifies COVID-19 Severity in ICU Patients |
|
| Relations |
| BioProject |
PRJNA912697 |
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