Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells [Illumina]

ABSTRACT: Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated System sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis. In this study, we obtained DNA methylation and RNA expression profiles of CD4+ T cells from 48 SSc patients and 16 healthy controls. Consequently, we identified 9112 and 3929 differentially methylated CpGs positions (DMPs) and differentially expressed genes (DEGs) respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing promoter capture Hi-C data, we confirmed 168 pairs of DMP-DEG physical interactions. Finally, utilizing SSc GWAS data, we identified three important SSc-associated susceptibility loci, CSK (rs1378942), IL12RB1 (rs2305743) and IKZF3-GSDMB (rs9303277), that physically interact with cg11062629-ULK3, cg10808810-JUND and cg19458020-CCR7 respectively. Overall, our study reveals a solid link between genetic, epigenetic and transcriptional deregulation in CD4+ T cells of SSc patients, providing further understanding to SSc pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146092 | GEO | 2020/09/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells [Affymetrix]

Project description:Epigenomic and transcriptomic analysis of Systemic Sclerosis CD4+ T cells reveals long range dysregulation of key inflammatory pathways mediated by disease-associated susceptibility loci range dysregulation of key inflammatory pathways mediated by disease-associated System sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis. In this study, we obtained DNA methylation and RNA expression profiles of CD4+ T cells from 48 SSc patients and 16 healthy controls. Consequently, we identified 9112 and 3929 differentially methylated CpGs positions (DMPs) and differentially expressed genes (DEGs) respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing promoter capture Hi-C data, we confirmed 168 pairs of DMP-DEG physical interactions. Finally, utilizing SSc GWAS data, we identified three important SSc-associated susceptibility loci, CSK (rs1378942), IL12RB1 (rs2305743) and IKZF3-GSDMB (rs9303277), that physically interact with cg11062629-ULK3, cg10808810-JUND and cg19458020-CCR7 respectively. Overall, our study reveals a solid link between genetic, epigenetic and transcriptional deregulation in CD4+ T cells of SSc patients, providing further understanding to SSc pathogenesis.

2020-09-04 | GSE146088 | GEO

Hypertrophic cardiomyopathy: data of transcriptome profiling and epigenome-wide DNA methylation analysis

Project description:Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease, and its pathogenesis is still being intensively studied to explain the reasons of significant genetic and phenotypic heterogeneity of the disease. To search for possible HCM modifier genes involved in the HCM development we first attempted to analyze gene expression profile coupled with DNA methylation profile in the hypertrophied myocardium of HCM patients; the control group consisted of patients with aortic stenosis. The transcriptome analysis identified significant differences in levels of 193 genes, most of which were underexpressed in HCM. The methylome analysis revealed 1755 nominally significant differentially methylated positions (DMPs), mostly hypomethylated in HCM. The clear differences in DNA methylation profiles between the studied groups indicate the involvement of this process in the formation of primary left ventricle hypertrophy in HCM. Based on gene ontology enrichment analysis, the majority of biological processes, overrepresented by both differentially expressed genes (DEGs) and DMP-containing genes, are involved in the regulation of locomotion and muscle structure development. The intersection of 193 DEGs and 978 DMP-containing genes pinpointed eight genes, expression of which differed between studied groups and correlated with methylation levels of the neighboring DMPs. Half of these genes (AUTS2, GIGYF1, PRRT1, and SLC17A7) were found underexpressed in HCM and involved in neurogenesis and synapse functioning. Our data suggesting the possible involvement of innervation-associated genes in HCM provide additional insights in the disease pathogenesis and expand the field of further research.

2022-12-14 | GSE207095 | GEO

Hypertrophic cardiomyopathy: data of transcriptome profiling and epigenome-wide DNA methylation analysis

2022-06-30 | GSE206978 | GEO

First characterization of the transcriptome of lung fibroblasts of SSc patients and healthy donors of African ancestry.

Project description:Systemic sclerosis (SSc) is a rare and devastating connective tissue disorder that results in fibrosis and vascular abnormalities that affect the skin and visceral organs, and SSc-associated pulmonary fibrosis (SSc-PF) is the leading cause of death amongst SSc patients. Racial disparity is noticeable in SSc as African Americans (AA) have a higher frequency and severity of diseases than European Americans (EA). Using RNAseq, we determined differentially expressed genes (DEGs) in primary pulmonary fibroblasts (pFBs) outgrown from SSc-PF lungs (SScL) and normal lungs (NL) of AA and EA patients to characterize the unique transcriptomic signatures of AA-NL and AA-SScL pFBs by performing a systems level analysis. We identified 69 DEGs in “AA-NL vs. EA-NL” and 384 DEGs in “AA-SScL vs. EA-SScL” comparisons, and only 7.5% DEGs were commonly deregulated in the “SScL vs. NL in AA and EA” disease mechanisms comparison. Surprisingly, we also identified a disease-like signature in AA-NL pFBs. Our data highlight that the transcriptome of AA pFBs is unique and may hold the key to understanding racial disparity in SSc-PF, the first step in developing efficacious therapeutic strategies.

2023-03-01 | GSE215841 | GEO

IgG from systemic sclerosis patients induce a profibrosing and serotype-dependent phenotype in normal dermal fibroblast: a multi-omics study

Project description:Autoantibodies (Aab) are frequent in systemic sclerosis (SSc). While recognized as potent biomarkers, their pathogenic role is much debated. This study explored the effect of purified IgG from SSc patients on the phenotype and function of healthy dermal fibroblast (FB) using an innovative multi-omics approach.

2022-06-29 | PXD025885 | Pride

Rheumatoid arthritis patients, both newly diagnosed and methotrexate treated, show more DNA methylation differences in CD4+ memory than in CD4+ naïve T cells

Project description:Differences in DNA methylation have been reported in B and T lymphocyte populations, including CD4+ T cells, isolated from rheumatoid arthritis (RA) patients when compared to healthy controls. CD4+ T cells are a heterogeneous cell type with subpopulations displaying distinct DNA methylation patterns. In this study, we investigated DNA methylation using reduced representation bisulfite sequencing in two CD4+ T cell populations (CD4+ memory and naïve cells) in three groups: newly diagnosed, disease modifying antirheumatic drugs (DMARD) naïve RA patients (N=11), methotrexate (MTX) treated RA patients (N=18), and healthy controls (N=9) matched for age, gender and smoking status. Analyses of these data revealed significantly more differentially methylated positions (DMPs) in CD4+ memory than in CD4+ naïve T cells (904 vs 19 DMPs) in RA patients compared to controls. The majority of DMPs (72%) identified in newly diagnosed and DMARD naïve RA patients with active disease showed increased DNA methylation (39 DMPs), whereas most DMPs (80%) identified in the MTX treated RA patients in remission displayed decreased DNA methylation (694 DMPs). Interestingly, we also found that about one third of the 101 known RA risk loci overlapped (+/- 500 kb) with the DMPs. Notably, introns of the UBASH3A gene harbour both the lead RA risk SNP and two DMPs in CD4+ memory T cells. Our results suggest that RA associated DNA methylation differences vary between the two T cell subsets, but are also influenced by RA characteristics such as disease activity, disease duration and/or MTX treatment.

2020-02-07 | GSE135770 | GEO

Epigenetic regulation of profibrotic macrophages in systemic sclerosis- associated interstitial lung disease

Project description:Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of death in patients with systemic sclerosis (SSc) with unclear pathogenesis and limited treatment options. Evidence strongly supports an important role for profibrotic, SPP1-expressing macrophages in SSc-ILD. We sought to define the transcriptome and chromatin structural changes of SPP1 SSc-ILD macrophages, so as to better understand their role in promoting fibrosis and to identify transcription factors associated with open chromatin driving their altered phenotype.

2022-09-02 | GSE212109 | GEO

Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy (mRNA)

Project description:Alterations in DNA methylation and gene expression have been implicated in the development of human dilated cardiomyopathy (DCM). In this study, we analyzed DNA methylomes (Infinium 450K HumanMethylation BeadChip) and transcriptomes (Infinium HT-12 v4) to characterize differentially methylated probes (DMPs) and differentially expressed genes (DEGs) between the left and right ventricles of human DCM. Illumina 450K array and HT-12 v4 array for the left, right ventricles

2016-08-15 | E-GEOD-81338 | biostudies-arrayexpress

Interspecies Comparative Genomics Identifies Optimal Mouse Models of Scleroderma (Tsk2)

Project description:Systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models of SSc that recapitulate distinct subsets of disease at the molecular level have not delineated. We applied interspecies comparative analysis of genomic data from multiple mouse models of SSc and patients with SSc to determine which animal models best reflect the SSc intrinsic gene expression subsets.

2015-08-13 | GSE71995 | GEO

Interspecies Comparative Genomics Identifies Optimal Mouse Models of Scleroderma (Tsk1/+)

2015-08-13 | GSE71991 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data