BioTile Identification of Differentially Methylated Regions in Tiling Microarray Data
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE43462 | GEO | 2013/05/24
SECONDARY ACCESSION(S): PRJNA186455
REPOSITORIES: GEO
Similar Datasets
Project description:This submission includes simulated data generated to test the BioTile algorithm's capability of identifying differentially methylated regions (DMR) located within an actual tiling array dataset. The data submitted was generated in silico to closely resemble DNA methylation profiles using Affymetrix Mouse Promoter 1.0R Tiling arrays. This simulated dataset of 40 arrays was generated using the "rnorm" function in R to create probe-wise distributions with the same mean and variance as our previously measured dataset (GSE43460).
2013-05-24 | E-GEOD-43462 | biostudies-arrayexpress
Project description:Differentially-methylated-regions (DMRs), pivotal to the diagnosis/pathogenesis of imprinting disorders, control imprinted gene expression with histone modifications; however, their establishment, numbers, boundaries, and crosstalk with chromatin remain elusive. Herein our global profiling reveals that although de novo methyltransferases DNMT3a/3b are required for locus-specific DMR maintenance, DNMT1 is required for all known DMRs. Based on the latter and the DMR concept, we have developed two novel approaches, “no restored DMRs (NORED)” and “Tag-mosaicity,” to identify/demarcate 31 known and 7 novel DMRs from 21 known loci, and 20 novel DMRs from novel loci. Tag-mosaicity analyses reveal the expected bimodal patterns of hypo/hypermethylated tags of known and new DMRs. Using Gtl2 locus, we demonstrate that methylation of DMRs controls H3K9me3 distribution to a long- range ”DMR-territory” that extends beyond our defined DMR boundary. These findings contrast that H3K9me3 controls CG methylation in Arabidopsis and Neurospora. Our analyses reveal that promoters of imprinted genes within a DMR-territory tend to have H3K4me2 and H3K9me3 with/without H3K27me3, whereas promoters outside have H3K27me3 and H3K4me2. Lastly, we confirmed that the transient DMR of Hcn2/Polrmt locus is conserved in the human genome. Our data link transient DMRs to epilepsy and chronic pain, Parkinson’s disease, Charcot-Marie-Tooth disease, and type 2 diabetes.
2016-09-15 | GSE61648 | GEO
Project description:Analysis of bisulfite sequencing data usually requires two tasks: to call methylated cytosines (mCs) in a sample, and to detect differentially methylated regions (DMRs) between paired samples. Although numerous tools have been proposed for mC calling, methods for DMR detection have been largely limited. Here, we present Bisulfighter, a new software package for detecting mCs and DMRs from bisulfite sequencing data. Bisulfighter combines the LAST alignment tool for mC calling, and a novel framework for DMR detection based on hidden Markov models (HMMs). Unlike previous attempts that depend on empirical parameters, Bisulfighter can use the expectation-maximization algorithm for HMMs to adjust parameters for each data set. We conduct extensive experiments in which accuracy of mC calling and DMR detection is evaluated on simulated data with various mC contexts, read qualities, sequencing depths and DMR lengths, as well as on real data from a wide range of biological processes. We demonstrate that Bisulfighter consistently achieves better accuracy than other published tools, providing greater sensitivity for mCs with fewer false positives, more precise estimates of mC levels, more exact locations of DMRs and better agreement of DMRs with gene expression and DNase I hypersensitivity. The source code is available at http://epigenome.cbrc.jp/bisulfighter.
| S-EPMC3973284 | biostudies-other
Project description:The addition of a methyl group to, typically, a cytosine-guanine dinucleotide (CpG) creates distinct DNA methylation patterns across the genome that can regulate gene expression. Aberrant DNA methylation of CpG sites has been associated with many psychiatric disorders including bipolar disorder (BD) and suicide. Using the SureSelectXT system, Methyl-Seq, we investigated the DNA methylation status of CpG sites throughout the genome in 50 BD individuals (23 subjects who died by suicide and 27 subjects who died from other causes) and 31 nonpsychiatric controls. We identified differentially methylated regions (DMRs) from three analyses: (a) BD subjects compared to nonpsychiatric controls (BD-NC), (b) BD subjects who died by suicide compared to nonpsychiatric controls (BDS-NC), and (c) BDS subjects compared to BD subjects who died from other causes (BDS-BDNS). One DMR from the BDS-NC analysis, located in ARHGEF38, was significantly hypomethylated (23.4%) in BDS subjects. This finding remained significant after multiple testing (PBootstrapped = 9.0 × 10-3 ), was validated using pyrosequencing, and was more significant in males. A secondary analysis utilized Ingenuity Pathway Analysis to identify enrichment in nominally significant DMRs. This identified an association with several pathways including axonal guidance signaling, calcium signaling, β-adrenergic signaling, and opioid signaling. Our comprehensive study provides further support that DNA methylation alterations influence the risk for BD and suicide. However, further investigation is required to confirm these associations and identify their functional consequences.
| S-EPMC8375453 | biostudies-literature
Project description:Obesity with adiposity is a common disorder in modern days, influenced by environmental factors such as eating and lifestyle habits and affecting the epigenetics of adipose-based gene regulations and metabolic pathways in colorectal cancer (CRC). We compared epigenetic changes of differentially methylated regions (DMR) of genes in colon tissues of 225 colon cancer cases (154 non-obese and 71 obese) and 15 healthy non-obese controls by accessing The Cancer Genome Atlas (TCGA) data. We applied machine-learning-based analytics including generalized regression (GR) as a confirmatory validation model to identify the factors that could contribute to DMRs impacting colon cancer to enhance prediction accuracy. We found that age was a significant predictor in obese cancer patients, both alone (p = 0.003) and interacting with hypomethylated DMRs of ZBTB46, a tumor suppressor gene (p = 0.008). DMRs of three additional genes: HIST1H3I (p = 0.001), an oncogene with a hypomethylated DMR in the promoter region; SRGAP2C (p = 0.006), a tumor suppressor gene with a hypermethylated DMR in the promoter region; and NFATC4 (p = 0.006), an adipocyte differentiating oncogene with a hypermethylated DMR in an intron region, are also significant predictors of cancer in obese patients, independent of age. The genes affected by these DMR could be potential novel biomarkers of colon cancer in obese patients for cancer prevention and progression.
| S-EPMC9142939 | biostudies-literature
Project description:Introduction: Nutriepigenetic markers are predictive responses associated with changes in human "surrounding" environmental conditions, which may influence metabolic diseases. Although rich in calories, Western diets could be linked with the deficiency of micronutrients, resulting in the downstream of epigenetic and metabolic effects and consequently in obesity. Zinc (Zn) is an essential nutrient associated with distinct biological roles in human health. Despite its importance in metabolic processes, little is known about the Zn-epigenetic. Thus, the present study aimed to identify the epigenetic variables associated with Zn daily ingestion (ZnDI) and serum Zinc (ZnS) levels in women with and without obesity. Materials and methods: this is a case-control, non-randomized, single-center study conducted with 21 women allocated into two groups: Control Group (CG), composed of 11 women without obesity, and Study Group (SG), composed of 10 women with obesity. Anthropometric measurements, ZnDI, and ZnS levels were evaluated. Also, the leukocyte DNA was extracted for DNA methylation analysis using the 450k Illumina BeadChips. The Epigenetic Clock was calculated by the Horvath method. The ChAMP package selected the Differentially Methylated Regions (DMRs). Results: The SG had lower ZnS levels than the CG. Moreover, in SG, the ZnS levels were negatively associated with the epigenetic age acceleration. The DMR analysis revealed 37 DMRs associated with ZnDI and ZnS levels. The DMR of the PM20D1 gene was commonly associated with ZnDI and ZnS levels and was hypomethylated in the SG. Conclusion: Our findings provide new information on Zn's modulation of DNA methylation patterns and bring new perspectives for understanding the nutriepigenetic mechanisms in obesity.
2022-01-21 | GSE193836 | GEO
Project description:BackgroundGrowing evidence shows that epigenetic modifications play a role in Alzheimer's disease (AD). We performed an epigenome-wide association study (EWAS) to evaluate the DNA methylation differences using postmortem superior temporal gyrus (STG) and inferior frontal gyrus (IFG) samples.ResultsSamples from 72 AD patients and 62 age-matched cognitively normal controls were assayed using Illumina© Infinium MethylationEPIC BeadChip. Five and 14 differentially methylated positions (DMPs) associated with pathology (i.e., Braak stage) with p value less than Bonferroni correction threshold of 6.79 × 10-8 in the STG and IFG were identified, respectively. These cytosine-phosphate-guanine (CpG) sites included promoter associated cg26263477 annotated to ABCA7 in the STG (p = 1.21 × 10-11), and cg14058329 annotated to the HOXA5/HOXA3/HOXA-AS3 gene cluster (p = 1.62 × 10-9) and cg09448088 (p = 3.95 × 10-9) annotated to MCF2L in the IFG. These genes were previously reported to harbor DMPs and/or differentially methylated regions (DMRs). Previously reported DMPs annotated to RMGA, GNG7, HOXA3, GPR56, SPG7, PCNT, RP11-961A15.1, MCF2L, RHBDF2, ANK1, PCNT, TPRG1, and RASGEF1C were replicated (p < 0.0001). One hundred twenty-one and 173 DMRs associated with pathology in the STG and IFG, respectively, were additionally identified. Of these, DMRs annotated to 30 unique genes were also identified as significant DMRs in the same brain region in a recent meta-analysis, while additional DMRs annotated to 12 genes were reported as DMRs in a different brain region or in a cross-cortex meta-analysis. The significant DMRs were enriched in promoters, CpG islands, and exons in the genome. Gene set enrichment analysis of DMPs and DMRs showed that gene sets involved in neuroinflammation (e.g., microglia differentiation), neurogenesis, and cognition were enriched (false discovery rate (FDR) < 0.05).ConclusionsTwenty-two DMPs and 30 DMRs associated with pathology were replicated, and novel DMPs and DMRs were discovered.
| S-EPMC7568396 | biostudies-literature
Project description:Imprinted genes are critical for normal human growth and neurodevelopment. We developed a strategy to identify new DNA differentially methylated regions (DMRs), a hallmark of imprinted genes. Using genome-wide methylation profiling, candidate DMRs were selected by identifying CpGs with putative allelic differential methylation in normal biparental tissues. In parallel, we looked for parent of origin-specific DNA methylation patterns in paternally derived human androgenetic complete hydatidiform mole (AnCHM), and maternally derived mature cystic ovarian teratoma (MCT). Using this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597. Most importantly, novel candidate imprinted genes were identified. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was validated by methylation analyses in humans. Further validation in mouse embryos showed that Axl was expressed preferentially from the maternal allele in a DNA methylation–dependent manner. We have analyzed 3 androgenetic complete hydatidiform mole (AnCHM), 16 white blood cell (WBC), 1 mature cystic ovarian teratoma (MCT), 5 placenta, and 1 lymphoblastoid cell line paternal UPD4 sample
2011-01-26 | E-GEOD-22091 | biostudies-arrayexpress
Project description:Imprinted genes are critical for normal human growth and neurodevelopment. We developed a strategy to identify new DNA differentially methylated regions (DMRs), a hallmark of imprinted genes. Using genome-wide methylation profiling, candidate DMRs were selected by identifying CpGs with putative allelic differential methylation in normal biparental tissues. In parallel, we looked for parent of origin-specific DNA methylation patterns in paternally derived human androgenetic complete hydatidiform mole (AnCHM), and maternally derived mature cystic ovarian teratoma (MCT). Using this approach, we found known DMRs associated with imprinted genomic regions as well as new DMRs for known imprinted genes, NAP1L5 and ZNF597. Most importantly, novel candidate imprinted genes were identified. The paternally methylated DMR for one candidate, AXL, a receptor tyrosine kinase, was validated by methylation analyses in humans. Further validation in mouse embryos showed that Axl was expressed preferentially from the maternal allele in a DNA methylation–dependent manner.
2011-01-26 | GSE22091 | GEO
Project description:DNA methylation differences capture substantial information about the molecular and gene-regulatory states among biological subtypes. Enrichment-based next generation sequencing methods such as MBD-isolated genome sequencing (MiGS) and MeDIP-seq are appealing for studying DNA methylation genome-wide in order to distinguish between biological subtypes. However, current analytic tools do not provide optimal features for analyzing three-group or larger study designs. MethylAction addresses this need by detecting all possible patterns of statistically significant hyper- and hypo- methylation in comparisons involving any number of groups. Crucially, significance is established at the level of differentially methylated regions (DMRs), and bootstrapping determines false discovery rates (FDRs) associated with each pattern. We demonstrate this functionality in a four-group comparison among benign prostate and three clinical subtypes of prostate cancer and show that the bootstrap FDRs are highly useful in selecting the most robust patterns of DMRs. Compared to existing tools that are limited to two-group comparisons, MethylAction detects more DMRs with strong differential methylation measurements confirmed by whole genome bisulfite sequencing and offers a better balance between precision and recall in cross-cohort comparisons. MethylAction is available as an R package at http://jeffbhasin.github.io/methylaction.
| S-EPMC4705678 | biostudies-literature