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Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [scRNA-Seq]

ABSTRACT: Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [scRNA-Seq]

PROVIDER: PRJNA755713 | ENA |

REPOSITORIES: ENA

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Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [scRNA-Seq]

Project description:Our work illustrates how high-resolution molecular and spatial profiling of COVID-19 patient tissues collected during rapid autopsies can serve as a hypothesisgenerating tool to identify key mediators driving the pathophysiology of COVID-19 for diagnostic and therapeutic target testing. Here we employ bulk RNA sequencing to identify key regulators of COVID-19 and list specific mediators for further study as potential diagnostic and therapeutic targets. We use single-nuclei RNA sequencing to highlight the diversity and heterogeneity of coronavirus receptors within the brain, suggesting that it will be critical to expand the focus from ACE2 to include other receptors, such as BSG and ANPEP, and we perform digital spatial profiling of lung and lymph node tissue to compare two patients with different clinical courses and symptomatology.

2021-08-20 | GSE182298 | GEO

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms

Project description:Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms

| PRJNA755706 | ENA

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [RNA-Seq]

2021-08-20 | GSE182297 | GEO

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [RNA-Seq]

Project description:Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [RNA-Seq]

| PRJNA755712 | ENA

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [Digital Spatial Profiling data]

2021-09-03 | GSE183356 | GEO

Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [Digital Spatial Profiling data]

Project description:Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms [Digital Spatial Profiling data]

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Molecular Profiling of COVID-19 Autopsies Uncovers Novel Disease Mechanisms

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-08-20 | GSE182299 | GEO

Molecular Profiling of Coronavirus Disease 2019 (COVID-19) Autopsies Uncovers Novel Disease Mechanisms.

Project description:Current understanding of coronavirus disease 2019 (COVID-19) pathophysiology is limited by disease heterogeneity, complexity, and a paucity of studies assessing patient tissues with advanced molecular tools. Rapid autopsy tissues were evaluated using multiscale RNA-sequencing methods (bulk, single-nuclei, and spatial RNA-sequencing next-generation sequencing) to provide unprecedented molecular resolution of COVID-19 induced damage. Comparison of infected/uninfected tissues revealed four major regulatory pathways. Effectors within these pathways could constitute novel therapeutic targets, including the complement receptor C3AR1, calcitonin receptor-like receptor, or decorin. Single-nuclei RNA sequencing of olfactory bulb and prefrontal cortex highlighted remarkable diversity of coronavirus receptors. Angiotensin-converting enzyme 2 was rarely expressed, whereas basigin showed diffuse expression, and alanyl aminopeptidase, membrane, was associated with vascular/mesenchymal cell types. Comparison of lung and lymph node tissues from patients with different symptoms (one died after a month-long hospitalization with multiorgan involvement, and the other died after a few days of respiratory symptoms) with digital spatial profiling resulted in distinct molecular phenotypes. Evaluation of COVID-19 rapid autopsy tissues with advanced molecular techniques can identify pathways and effectors, map diverse receptors at the single-cell level, and help dissect differences driving diverging clinical courses among individual patients. Extension of this approach to larger data sets will substantially advance the understanding of the mechanisms behind COVID-19 pathophysiology.

| S-EPMC8423774 | biostudies-literature

Epigenetic fingerprint of the SARS-CoV-2 infection in the lung of lethal COVID-19.

Project description:Interrogation of the DNA methylome from lung autopsies of 36 patients who died of SARS-CoV-2 vs 18 control non-COVID-19 individuals.

2023-11-02 | GSE224464 | GEO

Columbia University/NYP COVID-19 Lung Atlas

Project description:We profiled 116,314 cells using snRNA-seq of 20 frozen lungs obtained from 19 COVID-19 decedents and seven control patients with short postmortem interval (PMI) autopsies. The COVID-19 cohort comprises seven female and 12 male decedents, including 13 patients of Hispanic ethnicity, with an age range from 58 to >89 years who had acquired SARS-CoV-2 infection and succumbed to the disease. The average time from symptom onset to death was 27.5 days (range, 4–63 days). After rapid autopsy with a median PMI of 4 hours (range 2–9 hours) collected tissues were either flash-frozen or frozen following OCT (optimal cutting temperature) embedment and subjected to snRNA-seq using a droplet-based platform (10x Genomics). All included patients had underlying hypertensive disorder and frequently one or more additional co-morbidities associated with increased risk for severe COVID-19.

2021-04-29 | GSE171524 | GEO

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