Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1136239 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29839400.fastq.gz | Fastqsanger.gz | |||
| SRR29839401.fastq.gz | Fastqsanger.gz | |||
| SRR29839402.fastq.gz | Fastqsanger.gz | |||
| SRR29839403.fastq.gz | Fastqsanger.gz | |||
| SRR29839404.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 60 |
Similar Datasets
Project description:Recent efforts have identified genetic loci that are associated with coronavirus disease 2019 (COVID-19) infection rates and disease outcome severity. Translating these genetic findings into druggable genes that regulate COVID-19 host susceptibility is a critical next step. Using a translational genomics approach that integrates COVID-19 genetic susceptibility variants, multi-tissue genetically regulated gene expression (GReX) and perturbagen signatures, we identify IL10RB as the top key regulator of COVID-19 host susceptibility. In a series of validation steps we show that predicted GReX up-regulation of IL10RB and higher IL10RB expression in COVID-19 patient blood is associated with worse COVID-19 outcomes, and that in vitro IL10RB overexpression is associated with increased viral load and activation of disease-relevant molecular pathways.
2022-07-22 | GSE180622 | GEO
Project description:The heterogeneity in symptomatology and phenotypic profile attributable to COVID-19 is widely unknown. For the first time, our study provides the unique advantage of obtaining samples from the Middle Eastern population, an underrepresented region in genetic studies, and explore new genotypes in this population that will yield to novel genetic association. Specifically, we studied 646 patients in the United Arab Emirates. We describe strong association signals from genes on chromosomes 2, 3, 5, 11 and 13, which carry genes that are expressed in the lung, have been associated with tumour progression, emphysema, airway obstruction, and surface tension within the lung. Identifying genetic variants associated to COVID-19 susceptibility and severity may uncover novel biological insights into disease pathogenesis and identify mechanistic targets for therapeutic and vaccine development.
2022-06-03 | GSE184150 | GEO
Project description:To reveal genetic determinants of susceptibility to COVID-19 severity in the population and further explore potential immune-related factors, we performed a genome-wide association study on 284 confirmed COVID-19 patients (cases) and 95 healthy individuals (controls). We compared cases and controls of European (EUR) ancestry and African American (AFR) ancestry separately. To further exploring the linkage between HLA and COVID-19 severity, we applied fine-mapping analysis to dissect the HLA association with mild and severe cases.
2023-01-17 | GSE211972 | GEO
Project description:Individuals infected with the SARS-CoV-2 virus present with a wide variety of phenotypes ranging from asymptomatic to severe and even lethal outcomes. Past research has revealed a genetic haplotype on chromosome 3 that entered the human population via introgression from Neanderthals as the strongest genetic risk factor for the severe COVID-19 phenotype. However, the specific variants along this introgressed haplotype that contribute to this risk and the biological mechanisms that are involved remain unclear. Here, we assess the variants present on the risk haplotype for their likelihood of driving the severe COVID-19 phenotype. We do this by first exploring their impact on the regulation of genes involved in COVID-19 infection using a variety of population genetics and functional genomics tools. We then perform an locus-specific massively parallel reporter assay to individually assess the regulatory potential of each allele on the haplotype in a multipotent immune-related cell line. We ultimately reduce the set of over 600 linked genetic variants to identify 4 introgressed alleles that are strong functional candidates for driving the association between this locus and the severe COVID-19. These variants likely drive the locus’ impact on severity by putatively modulating the regulation of two critical chemokine receptor genes: CCR1 and CCR5. These alleles are ideal targets for future functional investigations into the interaction between host genomics and COVID-19 outcomes.
2023-02-09 | GSE176233 | GEO
Project description:Though SARS-CoV-2 primarily targets the respiratory system, patients and survivors can suffer neurological symptoms. Yet, an unbiased understanding of the cellular and molecular processes affected in the brains of COVID-19 patients is still missing. Here, we profile 65,309 single-nucleus transcriptomes from 30 frontal cortex and choroid plexus samples across 14 control (including 1 terminal influenza) and 8 COVID-19 patients. While a systematic analysis yields no molecular traces of SARS-CoV-2 in the brain, we observe broad cellular perturbations which predict that choroid plexus barrier cells sense and relay peripheral inflammation into the brain and show that peripheral T cells infiltrate the parenchyma. We discover COVID-19 disease-associated microglia and astrocyte subpopulations that share features with pathological cell states reported in human neurodegenerative disease. Synaptic signaling of upper-layer excitatory neurons—evolutionarily expanded in humans and linked to cognitive function—are preferentially affected in COVID-19. Across cell types, COVID-19 perturbations overlap with those in chronic brain disorders and reside in genetic variants associated with cognition, schizophrenia, and depression. Our findings and public dataset provide a molecular framework to understand COVID-19 related neurological disease observed now and which may emerge later.
2020-10-22 | GSE159812 | GEO
Project description:Genetic Determinants of Susceptibility to Severe COVID-19 Infection
| PRJNA671427 | ENA
Project description:Genetic Determinants of Susceptibility to Severe COVID-19 Infection
| PRJNA671428 | ENA
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:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to spread around the world with serious cases and deaths. It has also been suggested that different genetic variants in the human genome affect both the susceptibility to infection and severity of disease in COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) has been identified as a cell surface receptor for SARS-CoV and SARS-CoV-2 entry into cells. The construction of an experimental model system using human iPS cells would enable further studies of the association between viral characteristics and genetic variants. Airway and alveolar epithelial cells are cell types of the lung that express high levels of ACE2 and are suitable for in vitro infection experiments. Here, we show that human iPS cell-derived airway and alveolar epithelial cells are highly susceptible to viral infection of SARS-CoV-2. Using gene knockout with CRISPR-Cas9 in human iPS cells we demonstrate that ACE2 plays an essential role in the airway and alveolar epithelial cell entry of SARS-CoV-2 in vitro. Replication of SARS-CoV-2 was strongly suppressed in ACE2 knockout (KO) lung cells. Our model system based on human iPS cell-derived lung cells may be applied to understand the molecular biology regulating viral respiratory infection leading to potential therapeutic developments for COVID-19 and the prevention of future pandemics.
2024-08-21 | GSE275240 | GEO