DNA Methylation Profiles of Airway Epithelial Cells and PBMCs from Healthy, Atopic and Asthmatic Children.
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Dorota Stefanowicz
PROVIDER: E-GEOD-37853 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:DNA methylation profiling of airway epithelial cells (AECs) and peripheral blood mononuclear cells (PBMCs) from normal, atopic and asthmatic subjects. The Illumina GoldenGate Methylation Cancer Panel I was used to obtain DNA methylation profiles across approximately 1505 CpGs in AECs and PBMCs. Samples included 7 healthy, 9 atopic, 4 atopic asthmatic and 5 non-atopic asthmatic subjects. Please note that only some of the samples are matched (i.e. AECs and PBMCs from the same individual) due to DNA quality or sample collection (i.e. only one sample (AEC or PBMC) was collected from the patient).
2012-05-09 | GSE37853 | GEO
Project description:Genome wide DNA methylation profiling of normal whole blood samples. The data consist of 100 samples with Illumina HumanMethylation450 BeadChip data. Bisulphite converted DNA from the 100 samples were hybridized to the Illumina HumanMethylation450 BeadChip
2014-11-05 | E-GEOD-62992 | biostudies-arrayexpress
Project description:Inter-individual variability in DNA methylation has been hypothesized to contribute to complex phenotypes through epigenetic modulation of gene expression levels. Population epigenetic studies have been examining differences in DNA methylation in a variety of accessible tissues for association with specific diseases or exposures, but relatively little is known about how this inter-individual variation differs between tissues. This study presents an analysis of global DNA methylation differences between matched peripheral blood mononuclear cells and buccal epithelial cells; specifically it examines differential DNA methylation, probe-wise DNA methylation variance, and how methylation relates to a number of demographic factors across the two tissues. We found that peripheral blood mononuclear cells have overall higher DNA methylation than buccal epithelial cells, and regions of the genome that are differently methylated between the tissues tend to have low CpG density. We also discovered that although both tissues show extensive probe-wise variability, the specific regions and magnitude of variability differed between tissues. Finally, we observed that while both buccal epithelial and peripheral mononuclear blood cell DNA methylation was associated with gender, only methylation of the latter was associated with body mass index. The work presented here offers insight into variability of DNA methylation between individuals and across tissues and the suitability of buccal epithelial and peripheral mononuclear cells for the biological questions explored by epigenome-wide association studies in human populations. This cohort consist of genomic DNA extracted from the peripheral blood mononuclear cells and buccal epithelial cells of 25 individuals, bisulphite converted and hybridized to the Illumina GoldenGate Methylation Cancer Panel for genome wide DNA methylation profiling
2014-05-31 | E-GEOD-53396 | biostudies-arrayexpress
Project description:Obesity-associated asthma is recognized as a distinct entity with non-atopic T-helper 1 polarized systemic inflammation. DNA methylation is linked with T helper cell maturation and is associated with inflammatory patterns in asthma and obesity. However, it is unknown whether pathologic dysregulation of DNA methylation patterns occurs in obesity-associated asthma. Using HELP-tagging, we studied epigenome wide DNA methylation in peripheral blood mononuclear cells in 8 urban minority obese asthmatic pre-adolescent children and compared it to methylation in groups of 8 children with asthma alone, obesity alone and healthy controls. Ingenuity Pathway Analysis was used to identify biological pathways that were differentially targeted by methylation dysregulation. We found that obese asthmatics had distinct epigenome wide methylation patterns associated with decreased promoter methylation of a subset of genes, including RANTES, IL-12R and TBX21 and increased promoter methylation of CD23, a low affinity receptor for IgE and of TGFM-NM-2, inhibitor of Th cell activation. T cell signaling and macrophage activation were the two primary pathways that were selectively hypomethylated in obese asthmatics. These methylation patterns suggest that methylation is associated with non-atopic inflammation observed in obese asthmatic children compared to children with asthma alone and obesity alone. Our findings suggest a role of DNA methylation in the observed inflammatory patterns in pediatric obesity-associated asthma in minorities. 32 HpaII test
2014-04-14 | E-GEOD-43705 | biostudies-arrayexpress
Project description:Integrated profiling of somatic molecular alterations present in tumors is necessary to further our understanding of the tumorigenic process. We investigated the potential relationships between gene copy number alterations and DNA methylation profiles in a case series of pleural mesotheliomas (n=23). Gene copy number (CN) alterations profiled with 500K SNP arrays and DNA methylation measured at over 750 cancer-related genes with methylation bead-arrays were examined concomitantly. Considering each probed locus, there were no instances of significantly correlated CN alteration and methylation (no loci with Q < 0.05) and averaging loci over their associated genes revealed only two genes with significantly correlated CN and methylation alterations (Q < 0.04). In contrast to the lack of discrete correlations, the overall extent of tumor CN alteration was significantly associated with DNA methylation profile when comparing CN alteration extent among methylation profile classes (P < 0.02), and there was evidence that this association was partially attributable to prevalent allele loss observed at the maintenance DNA methyltransferase DNMT1. Taken together, this work indicates a strong association between global genetic and global epigenetic dysregulation in mesothelioma rather than a discrete, local coordination of gene inactivation, and further highlights the utility and necessity of integrative genomics approaches in cancer biology. Mesotheliomas were obtained following surgical resection at Brigham and Women’s Hospital through the International Mesothelioma Program from a pilot study conducted in 2002 and an incident case series beginning in 2005 as previously described (PMIDs: 19118007 and 19638575). All patients provided informed consent under the approval of the appropriate Institutional Review Boards. Clinical information, including histologic diagnosis was obtained from pathology reports. The study pathologist confirmed the histologic diagnoses and further assessed the percent tumor from resected specimens (mean >60%). DNA extraction and methylation analysis: DNA from fresh frozen tissue and matched whole blood was isolated with QIAamp DNA mini kit (Qiagen, Valencia, CA) following the manufacturer’s protocol. Tumor DNA was modified with sodium bisulfite using the EZ DNA Methylation Kit (Zymo Research, Orange, CA). Illumina GoldenGate® methylation bead arrays interrogated 1505 CpG loci associated with 803 cancer-related genes processed at the UCSF Institute for Human Genetics, Genomics Core Facility using methods described in (28). The GoldenGate methylation data used in the analysis has been previously described (PMIDs: 19118007 and 19638575).
2010-07-01 | E-GEOD-20989 | biostudies-arrayexpress
Project description:Purpose: Accumulating evidence indicates aberrant DNA methylation is closely related to oral carcinogenesis, and it has been shown that methylation changes might be used as prognostic biomarker in oral squamous cell carcinoma. Oral lichenoid disease (OLD) is the most common oral potentially malignant disorder in our region. In this study, we have performed a wide DNA methylation study of a series of oral lichenoid disease in order to assess the relevance of DNA methylation changes in this premalignant disorder. Experimental Design: Discovery phase utilized the Illumina Golden Gate Cancer Panel I in 51 OLD and 6 control samples. The differently methylated loci and the global DNA methylation surrogate LINE-1, were further validated in an independent sample set consisting in 160 OLD and 65 controls. Results: DNA methylation profiles of the OLD showed only minor significant differences when compared to controls. Conclusions: In summary, our data indicates that the frequency of aberrant DNA alteration is very low in OLD, which support the low rate of malignization of this oral potentially malignant disorder. Bisulphite-converted DNA from the 51 oral lichenoid disease samples and 6 control samples were hybridised to the Illumina GoldenGate Methylation Cancer Panel I.
2014-04-30 | E-GEOD-54210 | biostudies-arrayexpress
Project description:DNA Methylation Profiles of Airway Epithelial Cells and PBMCs from Healthy, Atopic and Asthmatic Children.
| PRJNA164689 | ENA
Project description:Rationale: Damage to airway epithelium is followed by deposition of extracellular matrix (ECM) and migration of adjacent epithelial cells. We have shown that epithelial cells from asthmatic children fail to heal a wound in vitro. Objectives: To determine whether dysregulated ECM production by the epithelium plays a role in aberrant repair in asthma. Methods: Airway epithelial cells (AEC) from children with asthma (n=36), healthy atopic (n=23) and healthy non-atopic controls (n=53) were investigated by microarray, gene expression and silencing, transcript regulation analysis and ability to close mechanical wounds. Results: Wound repair of AEC from healthy and atopic children were not significantly different and were both faster than AEC from asthmatics. Microarray analysis revealed differential expression of multiple gene sets associated with repair and remodeling in asthmatic AEC. Fibronectin (FN) was the only ECM component whose expression was significantly lower in asthmatic AEC. Expression differences were verified by qPCR and ELISA, and reduced FN expression persisted in asthmatic cells over passage. Silencing of FN expression in non-asthmatic AEC inhibited wound repair, while addition of FN to asthmatic AEC restored reparative capacity. Asthmatic AEC failed to synthesize FN in response to wounding or cytokine/growth factor stimulation. Exposure to 5â, 2âdeoxyazacytidine had no effect on FN expression and subsequent analysis of the FN promoter did not show evidence of DNA methylation. Conclusions: These data show that the reduced capacity of asthmatic epithelial cells to secrete FN is an important contributor to the dysregulated AEC repair observed in these cells. 16 arrays, 2 experimental groups, asthma atopic, AA, and healthy non-atopic, HN.
2010-04-12 | E-GEOD-18965 | biostudies-arrayexpress
Project description:Background: Epigenetic marks, like asthma, are heritable. They are influenced by the environment, direct the maturation of T cellslymphocytes, and have been shown to enhance the development of allergic airways disease in mice. Thus, we hypothesized that epigenetic marks are associated with allergic asthma in inner-city children. Methods: We compared methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy controls, using DNA and RNA from peripheral blood mononuclear cells (PBMCs) from inner city children aged 6-12 years with persistent atopic asthma children and healthy controls. Results were externally validated with the GABRIELA study population. Results: Comparing asthmatics (N=97) to controls (N=97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthmatics, including IL-13, RUNX3, and a number of specific genes relevant to natural killer cells (KIR2DL4, KIR2DL3, KIR3DL1, and KLRD1) and T cells lymphocytes (TIGIT). 14 differentially methylated regions (DMRs) were associated with the serum IgE concentration of IgE, including RUNX3. These results were internally and externally validated with a global methylation assessment using a different methodology in our inner-city cohort and an independent European cohort (GABRIELA). Hypo- and hypermethylated genes tended to be associated with increased and decreased gene expression, respectively (P<0.6x10-11 for asthma and ; P<0.01 for IgE). To further explore the relationship between methylation and gene expression, we created a matrix of genomic changes in methylation versus transcriptional changes (methyl eQTL) for asthma, and identified cis- and trans-regulated genes whose expression was related to asthma asthma-associated methylation marks. peripheral blood mononuclear cells (PBMCs) from 97 atopic asthmatic and 97 nonatopic nonasthmatic children
2015-02-02 | E-GEOD-40732 | biostudies-arrayexpress
Project description:Background: Epigenetic marks, like asthma, are heritable. They are influenced by the environment, direct the maturation of T cellslymphocytes, and have been shown to enhance the development of allergic airways disease in mice. Thus, we hypothesized that epigenetic marks are associated with allergic asthma in inner-city children. Methods: We compared methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy controls, using DNA and RNA from peripheral blood mononuclear cells (PBMCs) from inner city children aged 6-12 years with persistent atopic asthma children and healthy controls. Results were externally validated with the GABRIELA study population. Results: Comparing asthmatics (N=97) to controls (N=97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthmatics, including IL-13, RUNX3, and a number of specific genes relevant to natural killer cells (KIR2DL4, KIR2DL3, KIR3DL1, and KLRD1) and T cells lymphocytes (TIGIT). 14 differentially methylated regions (DMRs) were associated with the serum IgE concentration of IgE, including RUNX3. These results were internally and externally validated with a global methylation assessment using a different methodology in our inner-city cohort and an independent European cohort (GABRIELA). Hypo- and hypermethylated genes tended to be associated with increased and decreased gene expression, respectively (P<0.6x10-11 for asthma and ; P<0.01 for IgE). To further explore the relationship between methylation and gene expression, we created a matrix of genomic changes in methylation versus transcriptional changes (methyl eQTL) for asthma, and identified cis- and trans-regulated genes whose expression was related to asthma asthma-associated methylation marks. peripheral blood mononuclear cells (PBMCs) from 97 atopic asthmatic and 97 nonatopic nonasthmatic children
2015-02-02 | E-GEOD-40576 | biostudies-arrayexpress