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

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Bioinformatics: from nucleotids to networks (N2N)
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.
Keywords
NORMALIZATION, SUBSET-QUANTILE, HIGH-THROUGHPUT, GLIOBLASTOMA, PACKAGE, SITES, ARRAY, CANCER, MICROARRAY, ADJUVANT TEMOZOLOMIDE

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Chicago
De Meyer, Tim, Pierre Bady, Geert Trooskens, Sebastian Kurscheid, Jocelyne Bloch, Johan M Kros, Johannes A Hainfellner, et al. 2015. “Genome-wide DNA Methylation Detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: An Independent Large-scale Comparison.” Scientific Reports 5.
APA
De Meyer, Tim, Bady, P., Trooskens, G., Kurscheid, S., Bloch, J., Kros, J. M., Hainfellner, J. A., et al. (2015). Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison. SCIENTIFIC REPORTS, 5.
Vancouver
1.
De Meyer T, Bady P, Trooskens G, Kurscheid S, Bloch J, Kros JM, et al. Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison. SCIENTIFIC REPORTS. 2015;5.
MLA
De Meyer, Tim, Pierre Bady, Geert Trooskens, et al. “Genome-wide DNA Methylation Detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: An Independent Large-scale Comparison.” SCIENTIFIC REPORTS 5 (2015): n. pag. Print.
@article{7099059,
  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.},
  articleno    = {15375},
  author       = {De Meyer, Tim and Bady, Pierre and Trooskens, Geert and Kurscheid, Sebastian and Bloch, Jocelyne and Kros, Johan M and Hainfellner, Johannes A and Stupp, Roger and Delorenzi, Mauro and Hegi, Monika E and Van Criekinge, Wim},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {NORMALIZATION,SUBSET-QUANTILE,HIGH-THROUGHPUT,GLIOBLASTOMA,PACKAGE,SITES,ARRAY,CANCER,MICROARRAY,ADJUVANT TEMOZOLOMIDE},
  language     = {eng},
  pages        = {13},
  title        = {Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison},
  url          = {http://dx.doi.org/10.1038/srep15375},
  volume       = {5},
  year         = {2015},
}

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