Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

DNA Methylation of gDNA from blood and bronchoalveolar lavage of tuburbulosis patients with and without type 2 diabetes via Illumina Infinium MethylationEPIC array

ABSTRACT: Tuberculosis (TB) remains a leading cause of illness and death globally. Type 2 diabetes (T2D) patients are more likely to become infected with Mycobacterium tuberculosis (M.tb). When they are infected, they are more likely to develop active TB disease and to present with more severe TB and those who receive TB treatment are more likely to experience adverse treatment outcomes. Genomic DNA (gDNA) was isolated from unstimulated whole blood and bronchoalveolar lavage (BAL) cells. Analysis of methylation arrays was carried out following the Bioconductor ‘methylationArrayAnalysis’ workflow, using the IlluminaHumanMethylationEPICanno.ilm10b4.hg19 annotation set for Illumina MethylationEPIC arrays. Probes were excluded where detection p-value was <0.01, where they were located on the Y chromosome, or were annotated as containing SNPs or known to be cross-reacting. Probes on the X chromosome were retained as only females were included in this analysis. Background correction was carried out via the normal-exponential out-of-band (Noob) method and probe intensities were quantile normalized. To identify differentially methylated positions (DMPs), the data was filtered using the criteria shown in extended data figure 8. To permit comparison between DMPs a secondary cutoff of uncorrected p<0.01 and beta values >0.8 and <0.2 was retained. Gene set enrichment testing was carried out via the “gsameth” function in the missMethyl package using hallmark and GO gene sets from the MSigDB Molecular Signatures Database. The Hallmark (H) gene sets represent well-defined biological states or processes, whereas the GO (C5) set consists of genes annotated by the same ontology term.

ORGANISM(S): Homo sapiens

SUBMITTER: Adam Ewing

PROVIDER: E-MTAB-16151 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Publications

HUMAN ALVEOLAR MACROPHAGE FUNCTION IS IMPAIRED IN TUBERCULOSIS CONTACTS WITH DIABETES.

Kleynhans Léanie L Kunsevi-Kilola Carine C Tshivhula Happy H Webber Tariq T Keyser Alana A Prins Nicole N Snyders Candice I CI Shabangu Ayanda A Rozot Virginie V Kidd Martin M Zhang Hao H Cai Hong H Wang Yufeng Y Ewing Adam D AD Malherbe Stephanus T ST Azad Abul K AK Arnett Eusondia E Restrepo Blanca I BI Schlesinger Larry S LS Ronacher Katharina K

Research square 20241128

Type 2 diabetes (T2D) increases susceptibility to tuberculosis (TB) with the underlying mechanisms remaining unknown. To determine whether immune dysfunction in the lung contributes to TB susceptibility, we obtained paired human alveolar macrophages (HAMs) and monocyte-derived macrophages (MDMs) from TB-exposed individuals with/without T2D. Upon infection with Mycobacterium tuberculosis (M.tb), T2D-HAMs had more M.tb growth and produced more TNF. There were fewer neutrophils ...[more]

PMID: 39649174

Similar Datasets

Project description:Background: In a recent intervention study, the daily supplementation with 200 mg monomeric and oligomeric flavanols (MOF) from grape seeds for 8 weeks revealed a vascular health benefit in male smokers. The objective of the present study was to determine the impact of MOF consumption on the gene expression profile of leukocytes and to assess changes in DNA methylation. Methodology/Principal Findings: Gene expression profiles were determined using whole genome microarrays (Agilent) and DNA methylation was assessed using HumanMethylation450 BeadChips (Illumina). MOF significantly modulated the expression of 864 genes. The majority of the affected genes are involved in chemotaxis, cell adhesion, cell infiltration or cytoskeleton organisation, suggesting lower immune cell adhesion to endothelial cells. This was corroborated by in vitro experiments showing that MOF exposure of monocytes attenuates their adhesion to TNF-M-NM-1-stimulated endothelial cells. Nuclear factor-kappa B (NF-M-NM-:B) reporter gene assays confirmed that MOF decrease the activity of NF-M-NM-:B. Strong inter-individual variability in the leukocytesM-bM-^@M-^Y DNA methylation was observed. As a consequence, on group level, changes due to MOF supplementation could not be found. However, in individuals, significant changes in DNA methylation of genes involved in leukocyte rolling, adhesion and cytoskeleton remodelling were seen. Conclusion: Our study revealed that regular consumption of MOF modulates the expression of genes in immune cells which, however, cannot be correlated to alterations in the DNA methylome. Remarkably, at the individual level, genes related to leukocyte adhesion pathways present complex variation in DNA methylation. As such, the individual transcriptional and epigenetic modulation of genes involved in early manifestation of cardiovascular diseases constitutes important subcellular mechanisms by which MOF promote vascular health in humans. DNA methylation levels of blood samples from 10 subjects were assessed using HumanMethylation450 BeadChips (Illumina), both before and after a diet intervention with MOF.

Dataset Information

DNA Methylation of gDNA from blood and bronchoalveolar lavage of tuburbulosis patients with and without type 2 diabetes via Illumina Infinium MethylationEPIC array

Publications

HUMAN ALVEOLAR MACROPHAGE FUNCTION IS IMPAIRED IN TUBERCULOSIS CONTACTS WITH DIABETES.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets