Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

COHCAP MIRA / 450k Comparison [MIRA]

ABSTRACT: Compare a single sample run with two different technologies: Illumina 450k methylation array and MIRA on NimbleGen This data is being published as a technical test of utility for a novel integrative genomic algorithm (COHCAP) Keywords: HES-2

ORGANISM(S): Homo sapiens

SUBMITTER: Charles Warden

PROVIDER: E-GEOD-42734 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

COHCAP: an integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis.

Warden Charles D CD Lee Heehyoung H Tompkins Joshua D JD Li Xiaojin X Wang Charles C Riggs Arthur D AD Yu Hua H Jove Richard R Yuan Yate-Ching YC

Nucleic acids research 20130417 11

COHCAP (City of Hope CpG Island Analysis Pipeline) is an algorithm to analyze single-nucleotide resolution DNA methylation data produced by either an Illumina methylation array or targeted bisulfite sequencing. The goal of the COHCAP algorithm is to identify CpG islands that show a consistent pattern of methylation among CpG sites. COHCAP is currently the only DNA methylation package that provides integration with gene expression data to identify a subset of CpG islands that are most likely to r ...[more]

PMID: 23598999

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Project description:Melanoma genomes are often characterized by large numbers of sunlight-induced mutations. However, epigenetic alterations, in the form of aberrant DNA methylation patterns, are also abundant. Using MIRA-seq, we have carried out a comprehensive characterization of the DNA methylome in a series of metastatic melanoma samples and catalogued the methylation changes relative to normal melanocytes, the presumed cells of origin for these tumors. Individual melanoma tumors contained up to several thousand hypermethylated regions. We discovered 179 tumor-specific methylation peaks that were present in all (27/27) melanomas and may lend themselves as effective disease biomarkers, and 3124 methylation peaks were present in >40% of the tumors. We specifically examined the relationship between presence of the Polycomb mark, H3K27me3 in melanocytes and tumor-specific DNA methylation in melanoma. We found that 150 of the approximately 1,200 tumor-associated methylation peaks near transcription start sites (TSS) were H3K27me3-marked in melanocytes. Notably, DNA methylation in melanoma was specific for distinct H3K27me3 peaks rather than for H3K27me3-enriched regions with broad genomic coverage. Yet, there were also numerous H3K27me3 peak-associated TSS regions that were completely resistant to DNA methylation in tumors. Furthermore, a rather large group of genes became methylated in melanoma but lacked H3K27me3 in melanocytes. There was no relationship between presence of BRAF V600 mutations and the number of methylation peaks in individual tumors. Gene expression analysis showed a strong signature of upregulated immune response genes in melanomas presumably as a result of lymphocyte infiltration. Genes down-regulated in tumors were enriched for melanocyte differentiation and pigmentation factors. Overall, there was limited correlation between tumor-associated DNA methylation changes and changes in gene expression although distinct melanocyte differentiation genes including KIT, PAX3 and SOX10 became methylated and downregulated in melanoma. Using MIRA-Seq, DNA methylation profiles of 27 malignant melanomas and 3 primary cultured melanocyte samples were determined

Dataset Information

COHCAP MIRA / 450k Comparison [MIRA]

Publications

COHCAP: an integrative genomic pipeline for single-nucleotide resolution DNA methylation analysis.

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