The NCI60 DNA methylome
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE49143 | GEO | 2016/10/08
SECONDARY ACCESSION(S): PRJNA213141
REPOSITORIES: GEO
Similar Datasets
Project description:The 60 cell lines of the NCI Anti-Cancer Drug Screen (NCI60) constitute the most extensively characterized in vitro cancer cell model, and have been tested for sensitivity to over 100,000 potential chemotherapy agents. We have used the NCI60 cell lines and three additional lymphoblast lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis induction, and gene expression response by microarray analysis. While several studies have measured relative basal gene expression in the NCI60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. We found genes differentially regulated in cells with low survival after 2 or 8 Gy γ-rays. In contrast to reported basal gene expression patterns, little tissue-of-origin effect was detected in the radiation response pattern of gene expression, with the exception of lymphoblastoid cell lines. The most striking patterns in the radiation data were a set of genes upregulated preferentially in the p53 wild-type lines, and a set of cell-cycle regulatory genes strongly down-regulated across the entire NCI60 panel. The response of these genes to γ-rays appears to be unaffected by the myriad of genetic differences across this very diverse cell set, and represents the most universal gene expression response to ionizing radiation yet observed. Keywords: radiation response
2008-01-01 | GSE7505 | GEO
Project description:The 60 cell lines of the NCI Anti-Cancer Drug Screen (NCI60) constitute the most extensively characterized in vitro cancer cell model, and have been tested for sensitivity to over 100,000 potential chemotherapy agents. We have used the NCI60 cell lines and three additional lymphoblast lines to develop a database of responses of cancer cells to ionizing radiation. We compared clonogenic survival, apoptosis induction, and gene expression response by microarray analysis. While several studies have measured relative basal gene expression in the NCI60, this is the first comparison of large-scale gene expression changes in response to genotoxic stress. We found genes differentially regulated in cells with low survival after 2 or 8 Gy γ-rays. In contrast to reported basal gene expression patterns, little tissue-of-origin effect was detected in the radiation response pattern of gene expression, with the exception of lymphoblastoid cell lines. The most striking patterns in the radiation data were a set of genes upregulated preferentially in the p53 wild-type lines, and a set of cell-cycle regulatory genes strongly down-regulated across the entire NCI60 panel. The response of these genes to γ-rays appears to be unaffected by the myriad of genetic differences across this very diverse cell set, and represents the most universal gene expression response to ionizing radiation yet observed. Cells were exposed to 8Gy and gene expression ratios between untreated (Cy5) cells and exposed cells (Cy3) were measured four hours later
2010-05-27 | E-GEOD-7505 | biostudies-arrayexpress
Project description:Purpose: We characterized genome-wide DNA methylation profiles (methylome) in purified peripheral blood monocytes (PBMs) from 18 healthy postmenopausal Caucasian females aged 50-56 years. Methods: DNA methylome of Human Peripheral Blood Monocytes were generated by methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq), using Illumina GAIIx. The sequence reads that passed quality filters were analyzed using MEDIPS package. Targeted methylation validation analysis was performed by using MassARRAY EpiTYPER assays. Genome-wide gene expression profiles have been obtained for 7 of the 18 subjects by using Affymetrix 1.0 Human Exon ST arrays following the manufacturer's recommended protocols. Results: Using MeDIP-seq,a total of approximately 283 million reads were uniquely aligned to human genome (Build NCBI37, HG19), resulting in average ~16 million uniquely aligned high quality reads per sample. Distinct patterns were revealed at different genomic features. For instance, promoters were commonly (~58%) found to be unmethylated; whereas protein coding regions were largely (~84%) methylated. We found that approximately 24% CpG islands (CGIs) were highly methylated in PBMs. Further characterization of CGIs with respect to their relative locations to RefSeq genes revealed that the highly methylated CGIs were largely enriched (~89%) in CGIs located in gene bodies and intergenic regions. By integration of the methylome data with genome-wide PBM gene expression data, we found negative correlation between promoter methylation levels and gene transcription levels when comparing groups of genes with different expression levels, and this relationship was consistently observed across promoters with high to low CpG densities. Furthermore, we observed a modest but significant excess (permutation p<0.0001) of genes showing negative correlation between inter-individual promoter methylation and transcription levels, particularly for genes associated with CpG-rich promoters. Across the 18 individual PBM methylomes, we also identified genomic regions that were constitutively highly methylated in PBMs as well as regions showing large inter-individual variability. Conclusions: This study represents a comprehensive analysis of the PBM methylome and our data provides a valuable resource for future epigenomic and multi-omic studies exploring biological and disease-related regulatory mechanisms in PBMs.
2013-07-24 | GSE39604 | GEO
Project description:Purpose: We characterized genome-wide DNA methylation profiles (methylome) in purified peripheral blood monocytes (PBMs) from 18 healthy postmenopausal Caucasian females aged 50-56 years. Methods: DNA methylome of Human Peripheral Blood Monocytes were generated by methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq), using Illumina GAIIx. The sequence reads that passed quality filters were analyzed using MEDIPS package. Targeted methylation validation analysis was performed by using MassARRAY EpiTYPER assays. Genome-wide gene expression profiles have been obtained for 7 of the 18 subjects by using Affymetrix 1.0 Human Exon ST arrays following the manufacturer's recommended protocols. Results: Using MeDIP-seq,a total of approximately 283 million reads were uniquely aligned to human genome (Build NCBI37, HG19), resulting in average ~16 million uniquely aligned high quality reads per sample. Distinct patterns were revealed at different genomic features. For instance, promoters were commonly (~58%) found to be unmethylated; whereas protein coding regions were largely (~84%) methylated. We found that approximately 24% CpG islands (CGIs) were highly methylated in PBMs. Further characterization of CGIs with respect to their relative locations to RefSeq genes revealed that the highly methylated CGIs were largely enriched (~89%) in CGIs located in gene bodies and intergenic regions. By integration of the methylome data with genome-wide PBM gene expression data, we found negative correlation between promoter methylation levels and gene transcription levels when comparing groups of genes with different expression levels, and this relationship was consistently observed across promoters with high to low CpG densities. Furthermore, we observed a modest but significant excess (permutation p<0.0001) of genes showing negative correlation between inter-individual promoter methylation and transcription levels, particularly for genes associated with CpG-rich promoters. Across the 18 individual PBM methylomes, we also identified genomic regions that were constitutively highly methylated in PBMs as well as regions showing large inter-individual variability. Conclusions: This study represents a comprehensive analysis of the PBM methylome and our data provides a valuable resource for future epigenomic and multi-omic studies exploring biological and disease-related regulatory mechanisms in PBMs. DNA methylome of human peripheral blood monocytes were generated by MeDIP-seq, using Illumina GAIIx.
2013-07-24 | E-GEOD-39604 | biostudies-arrayexpress
Project description:Comprehensive characterization of the DNA methylome regulated by the treatment with glucocorticoids (GC) and retinoic acid (RA) alone and combined with AZA/SAHA and the relationship of these features with the status of BRG1 and MYC in lung cancer cell lines.
2016-09-08 | GSE66087 | GEO
Project description:DNA methylation plays a vital role in genome dynamics and, in the human genome, occurs predominantly at cytosine guanine dinucleotide (CpG) sites. The diploid haploid human genome analysed here contains around 2060 million CpG sites (methylome) where DNA methylation can vary, affecting many biological processes in health and disease. Using whole-genome bisulfite sequencing, we report the essentially complete (92.6282%) methylome of human peripheral blood mononuclear cells (PBMC) which constitute an important source for clinical blood tests world-wide. We find the majority of CpG sites (68.4% at false positive rate of 0.46%) and only <0.2% of non-CpG sites to be methylated, demonstrating that non-CpG cytosine methylation is negligible in human PBMC. Analysis of the PBMC methylome revealed a rich landscape of epigenomic data for 20 distinct features including regulatory, protein-coding, RNA gene coding, non-coding and repeat sequences. Alu element mobility, for instance, was found to negatively correlate with their methylation levels, emphasizing the critical role of DNA methylation in genome stability. Integration of our methylome data with the previously determined genome sequence of the same Asian individual analysed here, enabled a first assessment of allele-specific methylation (ASM) differences between the two haploid methylomes of any individual. Using a conservative cut-off (p <0.001), we identified 599 haploid differentially methylated regions (hDMRs) covering 287 genes. Of these, 76 genes had hDMRs within 2kb of their transcriptional start sites of which >80% displayed allele-specific expression (ASE) after random testing using TA clone sequencing of the same PBMC sample. These data show, that ASM is a recurrent phenomenon and highly correlated with ASE, suggesting that imprinting may be more common than previously thought. Our study not only provides a comprehensive resource for future epigenomic research but also demonstrates a paradigm of large-scale epigenomics studies through new sequencing technology.
2010-09-04 | GSE17972 | GEO
Project description:Examination of DNA methylome patterns in a larger cohort of ME/CFS samples using the Illumina Infinium HumanMethylation450 Beadchip Array
2017-03-15 | GSE93266 | GEO
Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.
2022-02-16 | PXD021821 | Pride
Project description:Genome-wide DNA methylation profiling of of 44 matched primary breast tumors and metastases. We sought to characterize methylome remodeling during regional metastasis. We profiled the DNA methylome (n=44) and transcriptome (n=36) of matched primary breast tumors and regional metastases.
2014-12-01 | GSE58999 | GEO