A Cell Epigenotype Specific Model for the Correction of Cellular Heterogeneity in the Brain
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41826 | GEO | 2013/02/22
SECONDARY ACCESSION(S): PRJNA178244
REPOSITORIES: GEO
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Project description:Cellular heterogeneity may bias cell type specific epigenetic patterns leading to a dramatic increase in false positive or negative findings in psychiatric epigenetic studies. To address this issue, we performed fluorescence activated cell sorting (FACS) of neuronal nuclei in post mortem frontal cortex 58 samples followed by Illumina HM450 microarray based DNA methylation profiling. We characterized the extent of neuron and glia specific DNA methylation variation independent of disease status and identified significant cell type specific epigenetic variation at 51% of loci. DNA methylation was profiled for sorted neuronal nuclei from post mortem frontal cortex of 29 major depression and 29 matched control samples using Illumina HM450 microarrays
2013-02-22 | E-GEOD-41826 | biostudies-arrayexpress
Project description:We performed a critical evaluation of the new Infinium MethylationEPIC BeadChip microarray. EPIC covers over 850,000 CpG sites, including >90% of the CpGs from the HumanMethylation450 (HM450) BeadChip and an additional 413,743 CpGs. Even though the additional probes improve the coverage of regulatory elements, including 58% of FANTOM5 enhancers, only 7% distal and 27% proximal ENCODE regulatory elements are represented. Detailed comparisons of regulatory elements from EPIC and whole-genome bisulphite sequencing data (WGBS) show that a single EPIC probe is not always informative for those distal regulatory elements showing variable methylation across the region. However, overall data from the EPIC array at single loci are highly reproducible across technical and biological replicates and demonstrate high correlation with HM450 and WGBS data. We show that the HM450 and EPIC arrays distinguish differentially methylated probes, but the absolute agreement depends on the threshold set for each platform.
2016-09-12 | GSE86831 | GEO
Project description:We performed a critical evaluation of the new Infinium MethylationEPIC BeadChip microarray. EPIC covers over 850,000 CpG sites, including >90% of the CpGs from the HumanMethylation450 (HM450) BeadChip and an additional 413,743 CpGs. Even though the additional probes improve the coverage of regulatory elements, including 58% of FANTOM5 enhancers, only 7% distal and 27% proximal ENCODE regulatory elements are represented. Detailed comparisons of regulatory elements from EPIC and whole-genome bisulphite sequencing data (WGBS) show that a single EPIC probe is not always informative for those distal regulatory elements showing variable methylation across the region. However, overall data from the EPIC array at single loci are highly reproducible across technical and biological replicates and demonstrate high correlation with HM450 and WGBS data. We show that the HM450 and EPIC arrays distinguish differentially methylated probes, but the absolute agreement depends on the threshold set for each platform.
2016-09-12 | GSE86829 | GEO
Project description:We performed a critical evaluation of the new Infinium MethylationEPIC BeadChip microarray. EPIC covers over 850,000 CpG sites, including >90% of the CpGs from the HumanMethylation450 (HM450) BeadChip and an additional 413,743 CpGs. Even though the additional probes improve the coverage of regulatory elements, including 58% of FANTOM5 enhancers, only 7% distal and 27% proximal ENCODE regulatory elements are represented. Detailed comparisons of regulatory elements from EPIC and whole-genome bisulphite sequencing data (WGBS) show that a single EPIC probe is not always informative for those distal regulatory elements showing variable methylation across the region. However, overall data from the EPIC array at single loci are highly reproducible across technical and biological replicates and demonstrate high correlation with HM450 and WGBS data. We show that the HM450 and EPIC arrays distinguish differentially methylated probes, but the absolute agreement depends on the threshold set for each platform.
2016-09-12 | GSE86832 | GEO
Project description:Identifying the sources of natural variation underlying metabolic differences between plants will enable a better understanding of plant metabolism and provide insights into the regulatory networks that govern plant growth and morphology. So far, however, the contribution of epigenetic variation to metabolic diversity has been largely ignored. In the present study, we utilized a panel of Arabidopsis thaliana epigenetic recombinant inbred lines (epiRILs) to assess the impact of epigenetic variation on the metabolic composition. Thirty epigenetic QTL (QTL epi ) were detected, which partly overlap with QTL epi linked to growth and morphology. In an effort to identify causal candidate genes in the QTL epi regions or their putative trans -targets we performed in silico small RNA and qPCR analyses. Differentially expressed genes were further studied by phenotypic and metabolic analyses of knockout mutants. Three genes were detected that recapitulated the detected QTL epi effects, providing evidence for epigenetic regulation in cis and in trans . These results indicate that epigenetic mechanisms impact metabolic diversity, possibly via small RNAs, and thus aid in further disentangling the complex epigenotype-phenotype map.
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Project description:DNA methylation has become increasingly recognized in the etiology of psychiatric disorders. Because brain tissue is not accessible in living humans, epigenetic studies are most often conducted in blood. Saliva is often collected for genotyping studies but is rarely used to examine DNA methylation because the proportion of epithelial cells and leukocytes varies extensively between individuals. The goal of this study was to evaluate whether saliva DNA is informative for studies of psychiatric disorders. Saliva and blood methylation was clearly distinguishable though there was positive correlation overall. There was little correlation in CpG sites within relevant candidate genes. Correlated CpG sites were more likely to occur in areas of low CpG density (i.e. CpG shores and open seas). There was more variability in CpG sites from saliva than blood, which may reflect its heterogeneity. Thus, this study provides a framework for using DNA methylation from saliva and suggests that DNA methylation of saliva may offer distinct opportunities for epidemiological and longitudinal studies of psychiatric traits. DNA methylation was assessed in saliva and blood samples from 64 adult African Americans. Both saliva and blood samples were collected from each participant. Saliva was stored in Oragene DNA sample collection kits (DNA Genotek), and blood was collected in EDTA vacuum tubes. DNA was extracted using the Puregene Genomic DNA kit (Invitrogen). DNA methylation was interrogated for each sample using the HumanMethylation450 BeadChip (Illumina). Analyses for tissue-specific DNA patterns were conducted using linear regression adjusted for appropriate covariates, including estimated cellular proportions. The estimated proportion of epithelial cells in saliva DNA ranged from 3-99% (median 26%). In blood, the estimated proportion of lymphocytes ranged from 25-70% (median 48%) and neutrophils ranged from 42-84% (median 58%). Methylation of 68.8% of all CpG sites differed relative to epithelial cell proportion (FDR<.05). Our results provide a framework for methylation studies in DNA extracted from saliva and highlight the importance of controlling for the proportion of epithelial and leukocyte cells. This presents an attractive opportunity for investigators that have already collected salivary DNA for genetic studies of psychiatric traits.
2014-09-24 | E-GEOD-61653 | biostudies-arrayexpress
Project description:Illumina Infinium Human Methylation (HM) BeadChips are a widely used platform for measuring genome-scale DNA methylation, particularly in relation to epigenetic GWAS (EWAS) studies. The methylation profile of human samples can be assessed accurately and reproducibly using the HM27 BeadChip (27,578 CpG sites) or its successor, the HM450 BeadChip (485,577 CpG sites). To date no mouse equivalent has been developed greatly hindering the application of this methodology to the wide range of valuable murine models of disease and development in existence. We found 1,308 and 13,715 probes from HM27 and HM450 BeadChip uniquely matched the reference mouse genome (mm9) respectively. We demonstrate reproducible measurements of DNA methylation at these probes in a range of mouse tissue samples and in a murine cell line model of acute myeloid leukaemia. In the absence of a mouse counterpart, the Infinium HumanMethylation BeadChip arrays have utility in carrying out methylation profiling in non-human species. GPL13534: 12 samples analysed in total. Two array replicates, two bisulfite conversion replicates and two biological replicates of mouse samples. 1 Human sample analysed in parallel. GPL8490: 3 samples
2013-06-21 | E-GEOD-43226 | biostudies-arrayexpress
Project description:Using the Infinium HM450 platform, we have performed a longitudinal study of DNA methylation at birth and age 18 months in DNA from buccal swabs from 10 monozygotic (MZ) and 5 dizygotic (DZ) twin pairs from the Peri/postnatal Epigenetic Twins Study (PETS) cohort.
2013-03-06 | GSE42700 | GEO
Project description:DNA-methylation is an important epigenetic feature in health and disease. Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). However, objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples obtained from 65 glioblastoma and 5 non-tumoral brain tissues, using a gold standard free Bayesian modeling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. Also the genome-wide characteristics were compared, revealing that the HM450 probes assess less than 10% of the regions identified as methylated by MethylCap-seq. Hence the latter method may detect more potentially relevant DNA-methylation, defined by either functional location or previously reported differentially methylated candidate regions. Our results therefore indicate that – at least for the tissue under study - both methodologies are complementary, with a higher sensitivity for HM450, but a far larger genome-wide coverage for MethylCap-seq. Note that here only the relevant MethylCap-seq data is deposited, for the HM450 data we refer to GEO (GSE60274).
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Project description:Genetic association studies provide evidence for a substantial polygenic component to schizophrenia, although the neurobiological mechanisms underlying the disorder remain largely undefined. Building on recent studies supporting a role for developmentally regulated epigenetic variation in the molecular etiology of schizophrenia, this study aimed to identify epigenetic variation associated with both a diagnosis of schizophrenia and elevated polygenic risk burden for the disease across multiple brain regions. Genome-wide DNA methylation was quantified in 262 post-mortem brain samples, representing tissue from four brain regions (prefrontal cortex, striatum, hippocampus and cerebellum) from 41 schizophrenia patients and 47 controls. We identified multiple disease-associated and polygenic risk score-associated differentially methylated positions and regions, many residing in the vicinity of genes previously implicated in schizophrenia including NCAM1, SYNPO, GBP4, PRDM9, GADD45B and DISC1. Our study represents the first analysis of epigenetic variation associated with schizophrenia across multiple brain regions and highlights the utility of polygenic risk scores for identifying molecular pathways associated with etiological variation in complex disease.
2016-11-10 | GSE89706 | GEO