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

Tim De Meyer (UGent) , Pierre Bady, Geert Trooskens (UGent) , Sebastian Kurscheid, Jocelyne Bloch, Johan M Kros, Johannes A Hainfellner, Roger Stupp, Mauro Delorenzi, Monika E Hegi, et al.
(2015) SCIENTIFIC REPORTS. 5.
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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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MLA
De Meyer, Tim, et al. “Genome-Wide DNA Methylation Detection by MethylCap-Seq and Infinium HumanMethylation450 BeadChips: An Independent Large-Scale Comparison.” SCIENTIFIC REPORTS, vol. 5, 2015, doi:10.1038/srep15375.
APA
De Meyer, T., Bady, P., Trooskens, G., Kurscheid, S., Bloch, J., Kros, J. M., … Van Criekinge, W. (2015). Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison. SCIENTIFIC REPORTS, 5. https://doi.org/10.1038/srep15375
Chicago author-date
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. https://doi.org/10.1038/srep15375.
Chicago author-date (all authors)
De Meyer, Tim, Pierre Bady, Geert Trooskens, Sebastian Kurscheid, Jocelyne Bloch, Johan M Kros, Johannes A Hainfellner, Roger Stupp, Mauro Delorenzi, Monika E Hegi, and Wim Van Criekinge. 2015. “Genome-Wide DNA Methylation Detection by MethylCap-Seq and Infinium HumanMethylation450 BeadChips: An Independent Large-Scale Comparison.” SCIENTIFIC REPORTS 5. doi:10.1038/srep15375.
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.
IEEE
[1]
T. De Meyer et al., “Genome-wide DNA methylation detection by MethylCap-seq and Infinium HumanMethylation450 BeadChips: an independent large-scale comparison,” SCIENTIFIC REPORTS, vol. 5, 2015.
@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}},
  keywords     = {{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://doi.org/10.1038/srep15375}},
  volume       = {{5}},
  year         = {{2015}},
}
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