Dataset Information

Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison.

ABSTRACT: Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). Objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples, i.e. 65 glioblastoma and 5 non-tumoral tissues. As MethylCap-seq coverages were limited, we focused on the inherent capacity of the methodology to detect methylated loci rather than a quantitative analysis. MethylCap-seq and HM450 data were dichotomized and performances were compared using a gold standard free Bayesian modelling procedure. While conditional specificity was adequate for both approaches, conditional sensitivity was systematically higher for HM450. In addition, genome-wide characteristics were compared, revealing that HM450 probes identified substantially fewer regions compared to MethylCap-seq. Although results indicated that the latter method can detect more potentially relevant DNA-methylation, this did not translate into the discovery of more differentially methylated loci between tumours and controls compared to HM450. Our results therefore indicate that both methodologies are complementary, with a higher sensitivity for HM450 and a far larger genome-wide coverage for MethylCap-seq, but also that a more comprehensive character does not automatically imply more significant results in biomarker studies.

SUBMITTER: De Meyer T

PROVIDER: S-EPMC4612737 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison.

De Meyer Tim T Bady Pierre P Trooskens Geert G Kurscheid Sebastian S Bloch Jocelyne J Kros Johan M JM Hainfellner Johannes A JA Stupp Roger R Delorenzi Mauro M Hegi Monika E ME Van Criekinge Wim W

Scientific reports 20151020

Two cost-efficient genome-scale methodologies to assess DNA-methylation are MethylCap-seq and Illumina's Infinium HumanMethylation450 BeadChips (HM450). Objective information regarding the best-suited methodology for a specific research question is scant. Therefore, we performed a large-scale evaluation on a set of 70 brain tissue samples, i.e. 65 glioblastoma and 5 non-tumoral tissues. As MethylCap-seq coverages were limited, we focused on the inherent capacity of the methodology to detect meth ...[more]

PMID: 26482909

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Project description:Hepatocellular carcinoma (HCC) incidence has increased in the US and also has one of the fastest growing death rates of any cancer. The purpose of the current study was to discover novel genome-wide aberrant DNA methylation patterns in HCC tumors that are predominantly HCV-related. Infinium HumanMethylation 450K BeadChip arrays were used to examine genome-wide DNA methylation profiles in 66 pairs of HCC tumor and adjacent non-tumor tissues. After Bonferroni adjustment, a total of 130,512 CpG sites significantly differed in methylation level in tumor compared with non-tumor tissues, with 28,017 CpG sites hypermethylated and 102,495 hypomethylated in tumor tissues. Absolute tumor/non-tumor methylation differences ? 20% were found in 24.9% of the hypermethylated and 43.1% of the hypomethylated CpG sites; almost 10,000 CpG sites have ? 30% DNA methylation differences. Most (60.1%) significantly hypermethylated CpG sites are located in CpG islands, with 21.6% in CpG shores and 3.6% in shelves. In contrast, only a small proportion (8.2%) of significantly hypomethylated CpG sites are situated in islands, while most are found in open sea (60.2%), shore (17.3%) or shelf (14.3%) regions. A total of 2,568 significant CpG sites (2,441 hypermethylated and 127 hypomethylated) covering 589 genes are located within 684 differentially methylated regions defined as regions with at least two significant CpG sites displaying > 20% methylation differences in the same direction within 250-bp. The top 500 significant CpG sites can significantly distinguish HCC tumor from adjacent tissues with one misclassification. Within adjacent non-tumor tissues, we also identified 75 CpG sites significantly associated with gender, 228 with HCV infection, 17,207 with cirrhosis, and 56 with both HCV infection and cirrhosis after multiple comparisons adjustment. Aberrant DNA methylation profiles across the genome were identified in tumor tissues from US HCC cases that are predominantly related to HCV infection. These results demonstrate the significance of aberrant DNA methylation in HCC tumorigenesis.

Project description:BackgroundDNA methylation is indispensible for normal human genome function. Currently there is an increasingly large number of DNA methylomic data being released in the public domain allowing for an opportunity to investigate the relationships between the DNA methylome, genome function, and human phenotypes. The Illumina450K is one of the most popular platforms for assessing DNA methylation with over 10,000 samples available in the public domain. However, accessing all this data requires downloading each individual experiment and due to inconsistent annotation, accessing the right data can be a challenge.DescriptionHere we introduce 'Marmal-aid', the first standardised database for DNA methylation (freely available at http://marmal-aid.org). In Marmal-aid, the majority of publicly available Illumina HumanMethylation450 data is incorporated into a single repository allowing for re-processing of data including normalisation and imputation of missing values. The database is accessible in two ways: (1) Using an R package to allow for incorporation into existing analysis pipelines which can then be easily queried to gain insight into the functionality of certain CpG sites. This is aimed at a bioinformatician with experience in R. (2) Using a graphical interface allowing general biologists to query a pre-defined set of tissues (currently 15) providing a reference database of the methylation state in these tissues for the 450,000 CpG sites profiled by the Illumina HumanMethylation450.ConclusionMarmal-aid is the largest publicly available Illumina HumanMethylation450 methylation database combining Illumina HumanMethylation450 data from a number of sources into a single location with a single common annotation format. This allows for automated extraction using the R package and inclusion into existing analysis pipelines. Marmal-aid also provides a easy to use GUI to visualise methylation data in user defined genomic regions for various reference tissues.

Dataset Information

Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison.

Publications

Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison.

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