Methylomic trajectories across human
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jon Mill
PROVIDER: E-GEOD-58885 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Background: Schizophrenia is a severe neuropsychiatric disorder that is hypothesized to result from disturbances in early brain development, and there is mounting evidence to support a role for developmentally-regulated epigenetic variation in the molecular etiology of the disorder. Here, we describe a systematic study of schizophrenia-associated methylomic variation in the adult brain and its relationship to changes in DNA methylation across human fetal brain development. Results: We profile methylomic variation in matched prefrontal cortex and cerebellum brain tissue from schizophrenia patients and controls, identifying disease-associated differential DNA methylation at multiple loci, particularly in the prefrontal cortex, and confirming these differences in an independent set of adult brain samples. Our data reveal discrete modules of co-methylated loci associated with schizophrenia that are enriched for genes involved in neurodevelopmental processes and include loci implicated by genetic studies of the disorder. Methylomic data from human fetal cortex samples, spanning 23 to 184 days post-conception, indicates that disease-associated differentially methylated positions are significantly enriched for loci at which DNA methylation is dynamically altered during human fetal brain development. Conclusions: Our data support the hypothesis that schizophrenia has an important early neurodevelopmental component, and suggest that epigenetic mechanisms may mediate these effects. 33 post-mortem brain (prefrontal cortex) samples (18 schizophrenia cases and 15 controls) were obtained from Douglas Bell-Canada Brain Bank (DBCBB), Montreal, Canada. Bisulfite converted DNA from these samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip v1.0.
2014-09-13 | E-GEOD-61380 | biostudies-arrayexpress
Project description:Alzheimer's disease is a progressive neurodegenerative disorder that is hypothesized to involve epigenetic dysfunction. We undertook an epigenome-wide association study across three independent brain tissue cohorts (total n = 999) to identify differential DNA methylation associated with neuropathology in the superior temporal gyrus and prefrontal cortex. We present robust evidence for elevated DNA methylation associated with AD neuropathology across an extended region spanning the HOXA gene cluster on chromosome 7. Prefrontal cortex and superior temporal gyrus tissue from 147 individuals with varying levels of AD pathology. DNA modifications for these samples were quantified using the Illumina Infinium Human 450K Methylation Array.
2016-08-01 | E-GEOD-80970 | biostudies-arrayexpress
Project description:Dynamic changes to the epigenome mediate key neurobiological and cognitive processes in the central nervous system, and also play a role in transcriptional regulation during brain development. Although the importance of DNA methylation in brain development is highlighted by the neurodevelopmental deficits associated with mutations in genes including methyl-CpG binding protein 2 (MECP2), our knowledge about the specific methylomic trajectories associated with human neurodevelopment is extremely limited. Here we report an analysis of genome-wide patterns of DNA methylation in 179 human fetal brain samples.
2014-12-19 | GSE58885 | GEO
Project description:A study to evaluate techniques for repairing DNA from formalin-fixed paraffin-embedded (FFPE) tissue samples by direct comparison of FFPE DNA repair methods prior to analysis on genome-wide methylation array to matched fresh frozen (FF) tissues. Formalin-fixed paraffin-embedded tissue from three colon adenocarcinoma samples were subjected to different FFPE-oriented DNA repair approaches and sequences, then compared with corresponding fresh frozen tissues. All samples were hybridized to the Illumina Infinium 450k Human Methylation BeadChip.
2014-12-17 | E-GEOD-59038 | biostudies-arrayexpress
Project description:The potential for epigenetic changes in host cells following microbial infection has been widely suggested, but few examples have been reported. We assessed genome-wide patterns of DNA methylation in human macrophage-like U937 cells following infection with Burkholderia pseudomallei, an intracellular bacterial pathogen and the causative agent of human melioidosis. Our analyses revealed significant changes in host cell DNA methylation, at multiple CpG sites in the host cell genome, following infection. Infection induced differentially methylated probes (iDMPs) showing the greatest changes in DNA methylation were found to be in the vicinity of genes involved in inflammatory responses, intracellular signalling, apoptosis and pathogen-induced signalling. A comparison of our data with reported methylome changes in cells infected with M. tuberculosis revealed commonality of differentially methylated genes, including genes involved in T cell responses (BCL11B, FOXO1, KIF13B, PAWR, SOX4, SYK), actin cytoskeleton organisation (ACTR3, CDC42BPA, DTNBP1, FERMT2, PRKCZ, RAC1), and cytokine production (FOXP1, IRF8, MR1). Overall our findings show that pathogenic-specific and pathogen-common changes in the methylome occur following infection. The human leukemic monocyte lymphoma cell line (U937, ATCC CRL-1593.2) was maintained in RPMI 1640 supplemented with 10% foetal bovine serum (FBS) at 37°C. U937 cells were differentiated to macrophage-like cells following exposure to 20 ng/ml (final concentration) of phorbol 12-myristate 13-acetate (PMA) for 48 hours at 37°C and differentiation evidenced by increased adherence to tissue culture flasks. Overnight cultures of B. pseudomallei K96243 were diluted in L-15 medium and added to differentiated U937 cells at a multiplicity of infection (MOI) of 10. Uninfected controls were overlaid with L15 medium only. The cells were then incubated at 37°C to allow infection. The cells were washed 3 times with PBS and incubated with fresh L15 medium containing 1mg/ml kanamycin to kill extracellular bacteria. At appropriate time points the cells were washed 3 times in warm PBS and lysed with 0.1% (vol/vol) Triton X-100. DNA was isolated using an AllPrep kit (Qiagen) and stored at -80ºC until required. DNA yield was measured using a Nanodrop instrument with measurements between 22.8 â 50.6 ng/ul. Two experiments were carried out using the above procedure. In Experiment 1, DNA was collected from uninfected and infected cells at 2 hours (T2), and 4 hours (T4) post infection (2 biological replicates and 2 technical replicates from each group). In Experiment 2, DNA was collected from uninfected and infected cells at 1 hour (T1), 2 hours (T2), 3 hours (T3) and 4 hours (T4) post infection (1 sample from each group). The DNA methylation profile was determined using the Infinium HumanMethylation450 BeadChip (450K) (Illumina Inc.) following the manufacturerâs instructions. The data was extracted and the initial analysis was performed using GenomeStudio (2010.3) methylation module (1.8.5). Quality control checks and quantile normalisation were implemented using WateRmelon. Samples with more than 1% of sites with a detection p-value greater than 0.05 were removed as were probes with 1% of samples with a detection p-value greater than 0.05. Probes were removed if they had a bead count less than 3 in 1% of samples. Cross-hybridizing probes were removed, leaving 425496 probes for analysis. Here we report DNA methylation profile of 18 samples (10 infected and 8 control).
2016-06-16 | E-GEOD-83379 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of oligodendroglial tumors (OTs) and five non tumoral brain tissue (NTBT) samples. The Illumina Infinium Human DNA methylation 450k Beadchip was used to obtain DNA methylation profiles across approximately 450,000 CpGs in tumoral samples. Samples included 46 OTs and 5 NTBT. Bisulphite converted DNA from the 51 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2014-09-06 | E-GEOD-61160 | biostudies-arrayexpress
Project description:Epigenetic processes such as DNA methylation play a key role in regulating tissue-specific and temporally-appropriate patterns of gene expression during development. Our knowledge about temporal changes to the epigenome in the developing human pancreas is limited. In this study we quantified levels of DNA methylation at over 800,000 sites in 112 human fetal pancreatic samples (51 male and 61 female) spanning from 6 to 21 post conception weeks (pcw). We found dramatic changes in DNA methylation across human pancreas development, with >22% of all methylation sites displaying significant changes across developmental age, with the majority of these sites showing stable levels of DNA methylation in the mature pancreas. Sites associated with developmental changes in DNA methylation during fetal pancreas development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across pancreas development. Weighted gene correlation network analysis (WGCNA) revealed modules of co-methylated loci associated with developmental age were enriched for genes involved in maturity onset diabetes of the young (MODY) and other metabolic phenotypes. A comparison with developmentally-dynamic patterns of DNA methylation in the developing human brain revealed significant tissue specific differences between the fetal pancreas and the fetal brain. Our data confirms the prenatal period to be a time of dynamic epigenetic changes. To our knowledge, this is the most extensive study of DNA methylation patterns in human fetal pancreatic development.
2024-02-19 | GSE244636 | GEO
Project description:Genome wide DNA methylation profiling of post-mortem human brain samples from both autistic individuals and nonautistic individuals. Samples of the frontal cortex (BA10) and cingulate cortex (BA24) were examined from each individual. Bisulphite converted DNA from the 45 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip
2014-09-03 | E-GEOD-53924 | biostudies-arrayexpress
Project description:We used the Illumina 450KMethylation BeadChip to measure DNA methylation at 485,512 loci across the genome for 40 postmortem brain samples. The purpose of our study was to identify differentially methylated regions (DMRs) associated with autism. Samples included 16 temporal cortex brain tissue samples (6 cases and 10 controls), 11 prefrontal cortex brain tissue samples (6 cases and 5 controls), and 13 cerebellum brain tissue samples (7 cases and 6 controls). We bisulfute converted DNA from the 40 brain tissue samples, processed, and hybridized them to the Illumina Infinium 450K HumanMethylation450 BeadChip as specificed by the manufacturer.
2013-12-12 | E-GEOD-53162 | biostudies-arrayexpress
Project description:We tested a hypothesis that prenatal alcohol exposure may lead to epigenetic alterations to the DNA resulting in attentional and cognitive alterations of the children. 6-9 year old children school children of the Franconian Cognition and Emotion Studies (FRANCES) cohort which were tested for an objective marker of PAE, ethyl glucuronide (EtG) in meconium at birth. 32 newborns were found to be exposed to alcohol with a threshold above 30 ng/g (EtG+) but without a FAS diagnosis. DNA for methylation analysis was extracted from buccal cells, DNA methylation was analyzed using the Infinium Human Methylation 450K BeadChip array (Illumina).
2018-05-12 | E-MTAB-6730 | biostudies-arrayexpress