Human cervical cells HELP-tagging cytosine methylation data
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76986 | GEO | 2016/08/22
SECONDARY ACCESSION(S): PRJNA309179
REPOSITORIES: GEO
Similar Datasets
Project description:We pursued the hypothesis that epigenetic regulators of transcription are involved in both the development and the progression of HPV-associated CIN. Using HELP-tagging, we performed the most comprehensive study to date of DNA methylation in HPV-associated cervical neoplasia, testing ~2 million loci throughout the human genome in biopsies from 78 HPV+ women, identifying changes starting in early CIN and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning early in the course of neoplastic disease and progressing with disease advancement. DNA methylation profiles for cervical biopsies of 19 normals, 20 CIN1, 16 CIN2/3, and 23 cervical cancers.
2016-08-22 | E-GEOD-76986 | biostudies-arrayexpress
Project description:We aimed to identify epigenetic regulators of transcription that may be involved in the development and the progression of HCV-associated HCC. Using HELP-tagging, we performed the highest resolution DNA methylation profiling of HCV-associated HCC to date, testing ~2 million loci throughout the human genome in liver biopsies from 30 patients, identifying changes starting in infected liver and maintained through carcinogenesis. We identified loci at which DNA methylation is consistently altered, beginning earlier in the course of neoplastic disease and progressing with disease advancement.
2016-10-17 | GSE82176 | GEO
Project description:Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies. 15 samples. HpaII libraries were compared to at least 3 MspI libraries from the same sample
2015-01-18 | E-GEOD-59200 | biostudies-arrayexpress
Project description:Using HELP-Tagging, we defined the cytosine methylation profiles of hematopoietic stem/progenitor cells (CD34+) from umbilical cord blood in 29 healthy newborns. We found substantial variation of DNA methylation to occur in human CD34+ hematopoietic stem and progenitor cells from different individuals. Empirical annotation of the genome of this cell type reveals the variability to be targeted to candidate promoters and to candidate enhancer sequences of genes expressed at lower levels. The variability of DNA methylation at candidate enhancers was low for housekeeping genes but high for genes associated with leukocyte differentiation. The enrichment of DNA methylation variability at loci with intermediate methylation values, occurring at apparently “poised” enhancers, suggests cell subpopulation heterogeneity between individuals as the basis for the epigenomic variability observed. The “meta-epigenome” present even in purified cells complicates the design and interpretation of epigenome-wide association studies, but also allows insights into the gene expression characteristics and the number of cell types comprising the cell population analyzed. One Sentence Summary: Variability in epigenomic patterns between different individuals occurs predominantly at promoters and enhancers, reflecting cell subpopulation heterogeneity.
2014-07-01 | GSE49836 | GEO
Project description:Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies.
2015-01-18 | GSE59200 | GEO
Project description:DNA methylation can be abnormally regulated in human disease and associated with effects on gene transcription that appear to be causally related to pathogenesis. The potential to use pharmacological agents that reverse this dysregulation is therefore an attractive possibility. To test how 5-aza-2M-bM-^@M-^Y-deoxycytidine (5-aza-CdR) influences the genome therapeutically, we exposed non-malignant cells in culture to the agent and used genome-wide assays to assess the cellular response. We found that cells allowed to recover from 5-aza-CdR treatment only partially recover DNA methylation levels, retaining an epigenetic M-bM-^@M-^\imprintM-bM-^@M-^] of drug exposure. We show very limited transcriptional responses to demethylation of not only protein-coding genes but also loci encoding non-coding RNAs, with a limited proportion of the induced genes acquiring new promoter activation within gene bodies. The data revealed an uncoupling of DNA methylation effects at promoters, with demethylation mostly unaccompanied by transcriptional changes. The limited panel of genes induced by 5-aza-CdR resembles those activated in other human cell types exposed to the drug, and represents loci targeted for Polycomb-mediated silencing in stem cells, suggesting a model for the therapeutic effects of the drug. Our results do not support the hypothesis of DNA methylation having a predominant role to regulate transcriptional noise in the genome, and indicate that DNA methylation acts only as part of a larger complex system of transcriptional regulation. The targeting of 5-aza-CdR effects with its clastogenic consequences to euchromatin raises concerns that the use of 5-aza-CdR has innate tumorigenic consequences, requiring its cautious use in diseases involving epigenetic dysregulation. Cytosine methylation profile of 4 different samples of HEK 293T treated with 5-aza-CdR
2015-02-13 | E-GEOD-62592 | biostudies-arrayexpress
Project description:DNA methylation can be abnormally regulated in human disease and associated with effects on gene transcription that appear to be causally related to pathogenesis. The potential to use pharmacological agents that reverse this dysregulation is therefore an attractive possibility. To test how 5-aza-2’-deoxycytidine (5-aza-CdR) influences the genome therapeutically, we exposed non-malignant cells in culture to the agent and used genome-wide assays to assess the cellular response. We found that cells allowed to recover from 5-aza-CdR treatment only partially recover DNA methylation levels, retaining an epigenetic “imprint” of drug exposure. We show very limited transcriptional responses to demethylation of not only protein-coding genes but also loci encoding non-coding RNAs, with a limited proportion of the induced genes acquiring new promoter activation within gene bodies. The data revealed an uncoupling of DNA methylation effects at promoters, with demethylation mostly unaccompanied by transcriptional changes. The limited panel of genes induced by 5-aza-CdR resembles those activated in other human cell types exposed to the drug, and represents loci targeted for Polycomb-mediated silencing in stem cells, suggesting a model for the therapeutic effects of the drug. Our results do not support the hypothesis of DNA methylation having a predominant role to regulate transcriptional noise in the genome, and indicate that DNA methylation acts only as part of a larger complex system of transcriptional regulation. The targeting of 5-aza-CdR effects with its clastogenic consequences to euchromatin raises concerns that the use of 5-aza-CdR has innate tumorigenic consequences, requiring its cautious use in diseases involving epigenetic dysregulation.
2015-02-13 | GSE62592 | GEO
Project description:Background: To perform epigenome-wide association studies in human disease, assays need to be comprehensive and quantitative while remaining cost-effective. We explored how the strengths of prior tag-based cytosine methylation assays based on massively-parallel sequencing can be maximised analytically. Results: We find that the use of the EcoP15I restriction enzyme to generate long tags and the normalisation of methylation-sensitive by methylation-insensitive restriction enzyme representations greatly improve assay performance. When exploring sources of bias, we find that the length of the restriction fragment has moderate effects on EcoP15I digestion, while base composition exerts minimal effects. We detail the analytical workflow that maximises the quantitative capabilities of this modified assay. Also revealed are polymorphic sequences in the genome that could confound microarray, bisulphite sequencing or mass spectrometry-based assays, and a position effect causing hypomethylation of transposable elements near gene promoters. Conclusions: The new combined assay, referred to as HELP-tagging, interrogates over 1.8 million loci in the human genome quantitatively with a single lane of Illumina sequencing. When the goal is to study not only CG-dense sequence but also the CG-depleted majority of the genome, this assay system should be suitable. Three MspI reference, one HpaII test
2010-04-12 | E-GEOD-19937 | biostudies-arrayexpress
Project description:Background: To perform epigenome-wide association studies in human disease, assays need to be comprehensive and quantitative while remaining cost-effective. We explored how the strengths of prior tag-based cytosine methylation assays based on massively-parallel sequencing can be maximised analytically. Results: We find that the use of the EcoP15I restriction enzyme to generate long tags and the normalisation of methylation-sensitive by methylation-insensitive restriction enzyme representations greatly improve assay performance. When exploring sources of bias, we find that the length of the restriction fragment has moderate effects on EcoP15I digestion, while base composition exerts minimal effects. We detail the analytical workflow that maximises the quantitative capabilities of this modified assay. Also revealed are polymorphic sequences in the genome that could confound microarray, bisulphite sequencing or mass spectrometry-based assays, and a position effect causing hypomethylation of transposable elements near gene promoters. Conclusions: The new combined assay, referred to as HELP-tagging, interrogates over 1.8 million loci in the human genome quantitatively with a single lane of Illumina sequencing. When the goal is to study not only CG-dense sequence but also the CG-depleted majority of the genome, this assay system should be suitable.
2010-04-12 | GSE19937 | GEO
Project description:Obesity-associated asthma is recognized as a distinct entity with non-atopic T-helper 1 polarized systemic inflammation. DNA methylation is linked with T helper cell maturation and is associated with inflammatory patterns in asthma and obesity. However, it is unknown whether pathologic dysregulation of DNA methylation patterns occurs in obesity-associated asthma. Using HELP-tagging, we studied epigenome wide DNA methylation in peripheral blood mononuclear cells in 8 urban minority obese asthmatic pre-adolescent children and compared it to methylation in groups of 8 children with asthma alone, obesity alone and healthy controls. Ingenuity Pathway Analysis was used to identify biological pathways that were differentially targeted by methylation dysregulation. We found that obese asthmatics had distinct epigenome wide methylation patterns associated with decreased promoter methylation of a subset of genes, including RANTES, IL-12R and TBX21 and increased promoter methylation of CD23, a low affinity receptor for IgE and of TGFM-NM-2, inhibitor of Th cell activation. T cell signaling and macrophage activation were the two primary pathways that were selectively hypomethylated in obese asthmatics. These methylation patterns suggest that methylation is associated with non-atopic inflammation observed in obese asthmatic children compared to children with asthma alone and obesity alone. Our findings suggest a role of DNA methylation in the observed inflammatory patterns in pediatric obesity-associated asthma in minorities. 32 HpaII test
2014-04-14 | E-GEOD-43705 | biostudies-arrayexpress