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PROVIDER: PRJNA338807 | ENA |
REPOSITORIES: ENA
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Project description:DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk [RNA-seq]
| PRJNA338808 | ENA
Project description:DNA methylation in lung cells is a key modulator of asthma endotypes and genetic risk
| PRJNA338804 | ENA
Project description:Childhood asthma is a complex disease historically defined by partially overlapping clinical features, including recurrent respiratory symptoms and reversible airway obstruction. However, the heterogeneity observed in clinical disease and airway pathology suggests that the “traditionally” defined asthma population is composed of multiple subgroups (i.e., endotypes), each with a distinct pathogenesis. Gene expression profiling of bronchial airway brushings identified the type 2-high asthma endotype, defined by excessive airway inflammation driven by type 2 cytokines, which was found in ~50% of subjects. Importantly, response to inhaled corticosteroid treatment was limited to this type 2-high endotype. The clinical utility of type 2-high asthma endotyping and the discovery of other endotypes have been limited by the need to perform an invasive bronchoscopy to obtain the bronchial brushings for analysis. Moreover, research bronchoscopies cannot be performed in children. Less invasive methods for the identification of asthma endotypes are needed. To this end, we found that the type 2-high asthma endotype can be identified by gene expression profiling of minimally invasive nasal airway epithelium brushings. Moreover, we found high nasal expression of the type 2 cytokine, IL-13,4 was associated with higher risk of asthma exacerbations among Puerto Ricans, who have the highest asthma morbidity and mortality in the U.S. Herein, we propose to use whole transcriptome sequencing of nasal airway epithelial brushings from Puerto Rican children with asthma to identify the type 2-high and other asthma endotypes, which relate to severity and drug response.
2020-07-13 | GSE152004 | GEO
Project description:Transcriptome analysis of whole blood from subjects with asthma and controls The presence or absence of type 2 inflammation (T2) biomarkers is used to identify T2-high and T2-low endotypes in the clinic. Despite the clinical relevance of these endotypes, the molecular mechanisms of T2-low asthma remain poorly understood. Specific microRNAs may regulate transcriptomic networks associated with asthma endotypes.
2025-12-01 | GSE287880 | GEO
Project description:Transcriptome analysis of whole blood from subjects with asthma and controls The presence or absence of type 2 inflammation (T2) biomarkers is used to identify T2-high and T2-low endotypes in the clinic. Despite the clinical relevance of these endotypes, the molecular mechanisms of T2-low asthma remain poorly understood. Specific microRNAs may regulate transcriptomic networks associated with asthma endotypes.
2025-12-01 | GSE287879 | GEO
Project description:Background: Asthma, a complex chronic lung disease affecting the airways, has striking disparities across ancestral groups, but the molecular underpinning of these differences is poorly understood and minimally studied. A major goal of the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) is to understand multi-omics signatures of asthma risk in the nasal epithelium focusing on populations of African ancestry. Methods: DNA methylation (DNAm) quantification was performed using Illumina’s Infinium MethylationEPIC array® using genomic DNA from nasal airway epithelial cells collected across the 4 US recruitment sites (Baltimore, Chicago, Denver, and Washington DC) for 331 subjects (N=149 asthma cases, N= 182 never asthmatic controls). We performed association analysis to identify eQTMs (CpG-gene associations) for DEGs limiting to CpGs ≤5kb from the transcription start site or within enhancer regions identified through promoter-capture HiC in bronchial epithelial cells. CpGs from significant eQTMs (p<0.05) were tested for differential methylation by asthma (DMCs) to assess the relative contribution of expression and methylation in asthma risk. All models were fully adjusted for ancestry, sampling site, and appropriate latent factors. Findings: Multi-omic analysis identified FKBP5 as a key contributor to asthma risk, where the association between nasal epithelium gene expression is likely regulated by methylation and is associated with increased use of inhaled corticosteroids. FKBP5 is a co-chaperone of glucocorticoid receptor signaling and known to be involved in drug response in asthma. Interpretation: Our analyses reveal genes and networks in asthma that are differentially expressed in nasal epithelium of current asthma cases of African ancestry in CAAPA. Importantly, this work reveals molecular dysregulation on three axes – increased Th2 inflammation, decreased capacity for wound healing, and impaired drug response – that may play a critical role in asthma within the African Diaspora.
2023-12-23 | GSE250513 | GEO
Project description:Comparison of lung function in C3H/HeJ and JF1/Msf strain mice to identify genetic risk factors for asthma and COPD.
2007-03-08 | E-MEXP-855 | biostudies-arrayexpress
Project description:Perinatal smoke/nicotine exposure alters lung development and causes asthma in exposed offspring, transmitted transgenerationally. The mechanism underlying the transgenerational inheritance of perinatal smoke/nicotine-induced asthma remains unknown, but germline epigenetic modulations may play a role. Using a well-established rat model of perinatal nicotine-induced asthma, we determined the DNA methylation pattern of spermatozoa of F1 rats exposed perinatally to nicotine in F0 gestation. To identify differentially methylated regions (DMRs), reduced representation bisulfite sequencing was performed on spermatozoa of F1 litters. The top regulated gene body and promoter DMRs were tested for lung gene expression levels, and key proteins involved in lung development and repair were determined. The overall CpG methylation in F1 sperms across gene bodies, promoters, 5’UTRs, exons, introns, and 3’UTRs was not affected by nicotine exposure. However, the methylation levels were different between the different genomic regions. 81 CpG sites, 16 gene bodies, and 3 promoter regions were differentially methylated. Gene enrichment analysis of DMRs revealed pathways involved in oxidative stress, nicotine response, alveolar and brain development, and cellular signaling. Among the DMRs, Dio1 and Nmu were the most hypermethylated and hypomethylated genes, respectively. Gene expression analysis showed that the mRNA expression and DNA methylation were incongruous. Key proteins involved in lung development and repair were significantly different (FDR < 0.05) between the nicotine and placebo-treated groups. Our data show that DNA methylation is remodeled in offspring spermatozoa upon perinatal nicotine exposure. These epigenetic alterations may play a role in transgenerational inheritance of perinatal smoke/nicotine induced asthma.
2021-05-17 | GSE173898 | GEO
Project description:Severe asthma is a clinically and physiologically heterogeneous disease. Benralizumab is a monoclonal antibody which binds the alpha chain of the interleukin-5 receptor and used for severe eosinophilic asthma worldwide. However, not all eosinophilic asthma patients will benefit from benralizumab due to heterogeneity of this disease. Therefore, we performed comprehensive gene expression analysis of whole blood cells that examine severe asthma disease heterogeneity in response to benralizumab. This study is the first to perform comprehensive transcriptome analysis of whole blood cells to identify transcriptomic endotypes of severe asthma clusters that correlate with benralizumab response. The identified transcriptomic endotypes of severe asthma clusters are associated with gene signatures of eosinophils and neutrophilis.
2023-04-15 | GSE148725 | GEO
Project description:Genetic variants associated with asthma are mostly in non-coding regions, so it is challenging to identify their target genes and the cellular contexts. Functional profiling of blood immune cell types has helped link asthma risk variants to functions. However, lung immune cells differ from those circulating in blood, and high-resolution functional genomic data of lung immune cells are lacking. Here we profiled single-cell multi-omics (RNA-seq and ATAC-seq) on lymphocytes of lung and spleen tissues. Cross-tissue comparison identified distinct transcriptomes for each immune cell type, but subtle differences in chromatin accessibility. We then assessed open chromatin regions of lung vs. blood, using a public dataset, for their enrichment of asthma risk. Strikingly, lung T cells show unique contributions to heritability of adult-onset (AOA) and childhood-onset asthma (COA), beyond blood T cells. We further identified 43 cis-regulatory elements (CREs) likely contributing to asthma risk. With enhancer-gene maps built from our single-cell data, we identified target genes for these CREs, including CCR4 and LRRC32 that show cell-type specific regulatory activities. These findings demonstrate the utility of single-cell multiomics to identify asthma risk genes and understand their cell-type specific functions.
2026-02-12 | GSE319044 | GEO