Validation of a DNA methylation microarray for 285,000 CpG sites of the mouse genome
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA807690 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:DNA methylation is the most well-known epigenetic mark and CpG methylation is critical for many cellular processes and human disorders. Cancer has highlighted the relevance of an aberrant DNA methylation landscape, including promoter CpG island hypermethylation-associated silencing of tumor suppressor genes and the presence of DNA hypomethylation blocks, but an altered DNA methylome is also now evident in other pathologies. However, progresses in delivering complete DNA methylation maps are compromised by the high price and labor and interpretation-consuming aspects of the single nucleotide methods nowadays used for whole genome bisulfite sequencing analyses. Following the success of the industry-leading HumanMethylation450 BeadChip (Infinium) methylation microarray that assess close to 450,000 CpG sites (450K), we have biologically and technically validated the newly developed MethylationEPIC BeadChip (Infinium) microarray that covers over 850,000 CpG methylation sites (850K). The 850K microarray contains >90% of the original 450K methylation sites, but add new 350,000 CpGs located in enhancers regions identified by the ENCODE and FANTOM5 projects. Herein, we show that the 850K DNA methylation array demonstrates high reproducibility for the previously analyzed CpG sites included in the 450K microarray; it is consistent among technical replicates; it is reliable in the matched study of fresh frozen vs formalin-fixed paraffin-embeded samples; and it is useful for both 5-methylcytosine and 5-hydroxymethylcytosine determination. The provided validation milestones highlights the value of the MethylationEPIC BeadChip as an informative and useful tool for the analyses of the DNA methylation profile of the human genome.
2015-12-18 | GSE75073 | GEO
Project description:We report the technical and biological validation of the newly developed Infinium Mouse Methylation BeadChip microarray that covers over 285,000 methylation sites.
2022-03-17 | GSE196902 | GEO
Project description:Stable maintenance of cytosine methylation is essential for mammalian biological processes such as gene transcription. This study introduced a RRBS-based quantitative method to identify CpG sites of high methylation fidelity (especially those 100% methylation fidelity sites). To separate the 100% methylation fidelity sites , we cultured the ARPE-19, Jurkat and SW1353 cells for lasting 10 generations, and we detected the methylation level of each CpG sites in the 20th generation and the 30th generation by performing reduced representation bisulfite sequencing (RRBS), to obtain the 100% methylation fidelity sites. The result shows that the number of overlapped fidelity methylation CpG sites of the two different time is smaller than number of each generation. Our results also showed that the proportion of high-fidelity 100% methylated sites in Jurkat and ARPE-19 cells is about 4.4% and 8.9%, and the proportion in SW1353 cells is 1.98%. The fidelity methylation sites obtained by the comparison of the two different time periods are the truly unchanged CpG sites during cell passage, which improves the reliability of the fidelity methylation sites. In summary, we provide new insights into the DNA methylation fidelity study.
2021-06-08 | GSE176335 | GEO
Project description:RRBS-based quantitative methylation analysis define 100% methylation fidelity CpG sites
| PRJNA735779 | ENA
Project description:RRBS-based quantitative methylation analysis define 100% methylation fidelity CpG sites
| PRJNA735782 | ENA
Project description:DNA methylation changes in neuroblastoma, a clinically-heterogeneous pediatric tumor, have been described essentially in promoter regions. We analyzed the DNA methylome of neuroblastoma using high-density microarrays and observed differential methylation not only in promoters but also in intragenic and intergenic regions at both CpG and non-CpG sites. These epigenetic changes showed a non-random distribution relative functional chromatin domains, and targeted development and cancer-related genes, relevant for neuroblastoma pathogenesis. CCND1, a gene overexpressed in neuroblastoma, showed hypomethylation of gene-body and upstream regulatory regions. Furthermore, tumors with diverse clinical-risk showed clear differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation was present in clinically-favorable tumors and affected genes such as ALK, where non-CpG methylation correlated with low gene expression. Finally, we identified CpG and non-CpG methylation signatures which correlated with patient’s age at time-points relevant for neuroblastoma clinical behavior, and targeted genes related to neural development and neural crest regulatory network We report on the first DNA methylomes of neuroblastoma tumors using high-density microarrays. DNA methylation changes in this pediatric tumor affected both CpG and non-CpG sites associated with developmental and cancer-related genes such as CCND1 and ALK. Our study also provides new insights into the molecular basis of the heterogeneous clinical behavior of neuroblastoma.
2015-06-03 | GSE54719 | GEO
Project description:Borderline personality disorder (BPD) is a complex psychiatric disease with an increased impact in the last years. While the diagnosis and therapy are well established, little is known on the pathogenesis of borderline personality disorder. Previously, a significant increase in DNA methylation of relevant neuropsychiatric genes in BPD patients has been reported. In our study we performed genome wide methylation analysis and revealed specific CpG sites that exhibited increased methylation in 26 BPD patients compared to 11 healthy controls. Bead chip technology and quantitative bisulfite pyrosequencing showed a significantly increased methylation at CpG sites of APBA2 (1.1 fold) and APBA3 (1.1 fold), KCNQ1 (1.6 fold), MCF2 (1.1 fold) and NINJ2 (1.2 fold) in BPD patients. For the CpG sites of GATA4 an increase in DNA methylation was observed, but was only significant in the bead chip assay. Moreover genome wide methylation levels of blood samples of BPD patients and control samples are similar. In summary, our results show a significant 1.26 fold average increase in methylation at the analyzed gene associated CpG sites in the blood of BPD patients compared to controls samples (p<0.001). This data may provide new insights into epigenetic mechanisms underlying the pathogenesis of BPD.
2014-02-01 | GSE52222 | GEO
Project description:Methylation of cytosine is an epigenetic mark involved in the regulation of transcription, usually associated with transcriptional repression. In mammals, methylated cytosines are found predominantly in CpGs but in plants non-CpG methylation (in the CpHpG or CpHpH contexts, where H is A, C or T) is also present and is associated with the transcriptional silencing of transposable elements. In addition, CpG methylation is found in coding regions of active genes. In the absence of the demethylase of lysine 9 of histone 3 (IBM1), a subset of body-methylated genes acquires non-CpG methylation. This was shown to alter their expression and affects plant development. It is not clear why only certain body-methylated genes gain non-CpG methylation in the absence of IBM1 and others do not. We described a link between CpG methylation and the establishment of methylation in the CpHpG context that explains the two classes of body-methylated genes. We provided evidence that external cytosines of CpCpG sites can only be methylated when internal cytosines are methylated and that CpCpG sites methylated in both cytosines promote spreading of methylation in the CpHpG context in genes protected by IBM1.
2017-01-04 | GSE89913 | GEO
Project description:DNA methylation changes in neuroblastoma, a clinically-heterogeneous pediatric tumor, have been described essentially in promoter regions. We analyzed the DNA methylome of neuroblastoma using high-density microarrays and observed differential methylation not only in promoters but also in intragenic and intergenic regions at both CpG and non-CpG sites. These epigenetic changes showed a non-random distribution relative functional chromatin domains, and targeted development and cancer-related genes, relevant for neuroblastoma pathogenesis. CCND1, a gene overexpressed in neuroblastoma, showed hypomethylation of gene-body and upstream regulatory regions. Furthermore, tumors with diverse clinical-risk showed clear differences affecting CpG and, remarkably, non-CpG sites. Non-CpG methylation was present in clinically-favorable tumors and affected genes such as ALK, where non-CpG methylation correlated with low gene expression. Finally, we identified CpG and non-CpG methylation signatures which correlated with patient’s age at time-points relevant for neuroblastoma clinical behavior, and targeted genes related to neural development and neural crest regulatory network We report on the first DNA methylomes of neuroblastoma tumors using high-density microarrays. DNA methylation changes in this pediatric tumor affected both CpG and non-CpG sites associated with developmental and cancer-related genes such as CCND1 and ALK. Our study also provides new insights into the molecular basis of the heterogeneous clinical behavior of neuroblastoma.
2015-06-03 | GSE54720 | GEO
Project description:Age-related CpG (AR-CpG) sites are currently the most promising molecular markers for age estimation. However, AR-CpG sites for the Han Chinese population have not yet been systematically identified. Besides, there may be high-performance AR-CpG sites beyond the coverage of the commonly used Illumina HumanMethylation450 BeadChip that covers over 450,000 CpG sites (450K), which accounts only 1.6% of CpG sites in the human genome. Therefore, we initiated a project to perform genome-wide methylation analysis on whole blood samples from 42 healthy Han Chinese individuals (21 males and 21 females, 18–62 years) using the newly developed Illumina Infinium MethylationEPIC array that assesses over 850,000 CpG sites (850K) to identify AR-CpG sites for forensic use systematically. The 850K methylation array contains > 90% of 450K CpG sites but adds 413,745 CpG sites. As expected, we not only replicated several high-performance AR-CpG sites previously discovered using the Illumina 450K BeadChip, such as cg16867656 (ELOVL2), cg22454769 (FHL2), and cg10501210 (C1orf132), but also identified 41 (60.3%), 34 (22.5%), and 382 (48.7%) novel AR-CpG sites from the methylation profiles of 21 males, 21 females, and all individuals, respectively.
2020-12-31 | GSE141682 | GEO