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Differential DNA methylation and changing cell type proportions as fibrotic stage progresses in NAFLD

ABSTRACT: Genome wide DNA methylation profiling of normal and NAFLD liver samples. The Illumina Infinium MethylationEPIC BeadChip kit was used to obtain DNA methylation profiles across CpGs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180474 | GEO | 2021/07/23

REPOSITORIES: GEO

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Differential DNA methylation and changing cell-type proportions as fibrotic stage progresses in NAFLD.

Project description:BackgroundNon-alcoholic fatty liver disease (NAFLD) is characterized by changes in cell composition that occur throughout disease pathogenesis, which includes the development of fibrosis in a subset of patients. DNA methylation (DNAm) is a plausible mechanism underlying these shifts, considering that DNAm profiles differ across tissues and cell types, and DNAm may play a role in cell-type differentiation. Previous work investigating the relationship between DNAm and fibrosis in NAFLD has been limited by sample size and the number of CpG sites interrogated.ResultsHere, we performed an epigenome-wide analysis using Infinium MethylationEPIC array data from 325 individuals with NAFLD, including 119 with severe fibrosis and 206 with no histological evidence of fibrosis. After adjustment for latent confounders, we identified 7 CpG sites whose DNAm associated with fibrosis (p < 5.96 × 10-8). Analysis of RNA-seq data collected from a subset of individuals (N = 56) revealed that gene expression at 288 genes associated with DNAm at one or more of the 7 fibrosis-related CpGs. DNAm-based estimates of cell-type proportions showed that estimated proportions of natural killer cells increased, while epithelial cell proportions decreased with disease stage. Finally, we used an elastic net regression model to assess DNAm as a biomarker of fibrotic stage and found that our model predicted fibrosis with a sensitivity of 0.93 and provided information beyond a model based solely on cell-type proportions.ConclusionThese findings are consistent with DNAm as a mechanism underpinning or marking fibrosis-related shifts in cell composition and demonstrate the potential of DNAm as a possible biomarker of NAFLD fibrosis.

| S-EPMC8340447 | biostudies-literature

Differential DNA methylation and changing cell type proportions as fibrotic stage progresses in NAFLD

Project description:Differential DNA methylation and changing cell type proportions as fibrotic stage progresses in NAFLD

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Inflammatory Cytokines shape a Changing DNA Methylome in Monocytes Mirroring Disease Activity in Rheumatoid Arthritis (patients)

Project description:Genome wide DNA methylation profiling of monocytes from healthy donors and rheumatoid arthritis patients. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in CD11b+CD33+CD15neg monocytes isolated from PBMCs of 17 healthy donors and 47 rheumatoid arthritis patients with different disease activity scores (DAS28).

2019-12-31 | GSE134429 | GEO

Inflammatory Cytokines shape a Changing DNA Methylome in Monocytes Mirroring Disease Activity in Rheumatoid Arthritis (in vitro)

Project description:Genome wide DNA methylation profiling of CD11b+CD33+ cells after treatment with different cytokines. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs in CD11b+CD33+ cells isolated from PBMCs treated in vitro for 4 days with TNF-alpha, IFN-alpha, IFN-gamma or control.

2019-12-31 | GSE134425 | GEO

Genome wide methylation analysis of 16 melanoma cell lines

Project description:Genome wide DNA methylation profiling of sixteen melanoma cell lines. The Illumina Infinium MethylationEPIC DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs from the cell lines at baseline.

2018-08-31 | GSE114721 | GEO

ELOVL2 is a novel tumor suppressor attenuating tamoxifen resistance in breast cancer via suppressing the AKT pathway [methylation 850K]

Project description:Genome wide DNA methylation profiling of tamoxifen-resistant(Tam-R) breast cancer cell line MCF-7. The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across approximately 850,000 CpGs.

2020-06-12 | GSE132616 | GEO

Genomic Evaluation of Multiparametric Magnetic Resonance Imaging -visible and -nonvisible Lesions in Clinically Localized Prostate Cancer

Project description:Genome wide DNA methylation profiling of normal and tumour prostate samples. The Illumina Infinium MethylationEPIC Human DNA methylation oligonucleotide beads was used to obtain DNA methylation profiles across approximately 850,000 CpGs. Comparative assessment was carried out.

2018-12-01 | GSE101908 | GEO

DNA methylation of diabetic and normal human limbal epithelial cells

Project description:Genome wide DNA methylation profiling of primary cultures of normal and diabetic corneolimbal epithelial cells. The Illumina Infinium MethylationEPIC Human DNA methylation Beadchip v1.0 B4 was used to obtain DNA methylation profiles across approximately 850,000 CpGs.

2023-04-15 | GSE229328 | GEO

Methylation array analysis of FACS-sorted, normal human mammary epithelial subtypes

Project description:The Illumina Infinium MethylationEPIC BeadChip was used to obtain DNA methylation profiles across >850,000 CpGs in mammary epithelial cell subsets isolated from two cosmetic breast reduction mammoplasty specimens.

2022-04-02 | GSE199579 | GEO

Circulating cell-free DNA methylation mirrors alterations in cerebral patterns in epilepsy

Project description:DNA methylation progiling of circulaing cell-free DNA isolatated from serum of 12 MTLE patients and 11 healthy controls. The Illumina Infinium MethylationEPIC Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs.

2023-01-11 | GSE208758 | GEO

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