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Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus [RNA-Seq]

ABSTRACT: We generated genome-wide gene expression data (RNAseq) from cultured airway epithelial cells exposed to rhinovirus (RV) and a vehicle control (48 hour treatment). This data was generated in combination with genome-wide DNA methylation data (RNAseq) and genotypes from the same individuals.

ORGANISM(S): Homo sapiens

PROVIDER: GSE172367 | GEO | 2021/06/01

REPOSITORIES: GEO

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Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus [Methylation array]

Project description:We generated genome-wide DNA methylation data from cultured airway epithelial cells exposed to rhinovirus (RV) and a vehicle control (48 hour treatment). This data was generated in combination with genome-wide expression data (RNAseq) and genotypes from the same individuals.

2021-06-01 | GSE172365 | GEO

ATAC-seq studies of Rhinovirus Response in asthma cases and non-asthma controls

Project description:There is a life-long relationship between rhinovirus (RV) infection and the development and clinical manifestations of asthma. In this study we demonstrate that cultured primary bronchial epithelial cells from adults with asthma (n = 9) show different transcriptional and chromatin responses to RV infection compared to those without asthma (n = 9). Both the number and magnitude of transcriptional and chromatin responses to RV were muted in cells from asthma cases compared to controls. Pathway analysis of the transcriptionally responsive genes revealed enrichments of apoptotic pathways in controls but inflammatory pathways in asthma cases. Using promoter capture Hi-C we tethered regions of RV-responsive chromatin to RV-responsive genes and showed enrichment of these regions and genes at asthma GWAS loci. Taken together, our studies indicate a delayed or prolonged inflammatory state in cells from asthma cases and highlight genes that may contribute to genetic risk for asthma.

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RNA-seq studies of Rhinovirus Response in asthma cases and non-asthma controls

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Multi-omics colocalization with genotype-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus

Project description:We generated imputed genotypes from 104 individuals from whole blood or airway epithelial cells. This data was generated in combination with genome-wide DNA methylation data (RNAseq) and genotypes from the same individuals as part of an expression and DNAm quantitatively loci study.

2021-09-04 | PRJEB47290 | EVA

Eosinophil-mediated suppression and Anti-IL-5 enhancement of plasmacytoid dendritic cell interferon responses in asthma

Project description:Blood plasmacytoid dendritic cells (pDCs) purified from anonymous donors were stimulated ex vivo with rhinovirus-16 (RV) in the presence or absence of eosinophil supernatants. Purified pDCs from 8 individuals with moderate-severe asthma, treated or not treated with anti-IL-5/5Rα therapy, were cultured with or without RV. Transcriptome analysis revealed global repression of pDC IFN response patterns by eosinophils, most notably in basal expression of interferon stimulated genes (ISGs). Increased RV-induced IFNα secretion and transcription as well as increased basal ISG expression was detected in pDCs from participants treated with anti-IL-5/5Rα therapy. Our findings highlight a novel mechanism through which T2 inflammation regulates pDC IFNα responses relevant to RV respiratory infections in the context of eosinophilic airway disease and suggest one potential mechanism through with eosinophil-depleting therapies may reduce the severity of RV illness.

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Gene expression data from uninfected and rhinovirus-infected peripheral blood mononuclear cells from 98 individuals

Project description:Rhinovirus (RV) is the most prevalent human respiratory virus. Each year, RV infects billions of people and is responsible for at least half of all common colds, the most common illness of humans. RV infection also affects the morbidity of a range of respiratory illnesses, such as bronchiolitis, pneumonia, asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Despite its biological importance and public health significance, little is known about the genetic architecture of response to RV. To address this, we obtained genome-wide genotype and gene expression data in uninfected and RV-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. We characterized gene expression differences in response to RV infection and mapped expression quantitative trait loci (eQTLs) in both uninfected and RV-infected PBMCs. The study includes data from uninfected and rhinovirus-infected peripheral blood mononuclear cells (PBMCs) from 98 individuals. Twenty ml of blood was drawn from each participant. PBMCs were isolated from whole blood samples by Ficoll-Paque separation. From each subject, 4 million PBMCs were treated with media alone for 24 hours and 4 million PBMCs were treated with media containing RV16 for 24 hours. The multiplicity of infection was 10 plaque-forming units per cell. Total RNA was extracted after 24-hour incubation, using the RNeasy Plus Mini Kit; concentrations were measured on a Nanodrop ND-100 Spectrophotometer and quality was assessed using an Agilent 2100 Bioanalyzer. Genome wide gene expression profiling of uninfected and rhinovirus-infected PBMCs was obtained using Illumina HumanHT-12 v4 Expression BeadChip arrays at the University of Chicago Functional Genomics Core.

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Multi-omics co-localization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus

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

2021-06-01 | GSE172368 | GEO

A mouse model of human coronavirus HCoV-NL63 infection: comparison with rhinovirus-A1B

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Gene expression data from uninfected and rhinovirus-infected peripheral blood mononuclear cells from 98 individuals

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Lipopolysaccharide modulates rhinovirus-induced chemokine secretion in monocytes and macrophages.

Project description:Rhinovirus (RV) infection has been shown to exacerbate asthma. Understanding of the underlying mechanisms by which RV infections provoke airway inflammation and remodeling in asthma may offer significant insight into asthma pathogenesis and exacerbations as well as offer opportunities for improved disease management. Expression analysis of RV A16-treated primary peripheral blood monocytes from human donors was performed to determine what pattern of gene expression is associated with RV infection of monocytes in vitro.

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