High density DNA methylation array with single CpG site resolution

Bibikova, Marina; Barnes, Bret; Tsan, Chan; Ho, Vincent V.; Klotzle, Brandy; Le, Jennie; Delano, David L.; Zhang, Lu; Schroth, Gary P.; Gunderson, Kevin L.; Fan, Jian‐Bing; Shen, Richard

doi:10.1016/j.ygeno.2011.07.007

Cited by 1,486 publications

(1,470 citation statements)

References 42 publications

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“…DNA was whole-genome amplified, enzymatically fragmented, purified, and applied to the Illumina Infinium HumanMethylation450 BeadChips (Illumina, San Diego, CA) according to the Illumina methylation protocol [11,12]. Both EPIC and 450K chips were analyzed using the Illumina Hi-Scan system.…”

Section: Methodsmentioning

confidence: 99%

Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

et al. 2018

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Analysis of DNA methylation helps to understand the effects of environmental exposures as well as the role of epigenetics in human health. Illumina, Inc. recently replaced the HumanMethylation450 BeadChip (450K) with the EPIC BeadChip, which nearly doubles the measured CpG sites to >850,000. Although the new chip uses the same underlying technology, it is important to establish if data between the two platforms are comparable within cohorts and for meta-analyses. DNA methylation was assessed by 450K and EPIC using whole blood from newborn (n = 109) and 14-year-old (n = 86) participants of the Center for the Health Assessment of Mothers and Children of Salinas. The overall per-sample correlations were very high (r >0.99), although many individual CpG sites, especially those with low variance of methylation, had lower correlations (median r = 0.24). There was also a small subset of CpGs with large mean methylation β-value differences between platforms, in both the newborn and 14-year datasets. However, estimates of cell type proportion prediction by 450K and EPIC were highly correlated at both ages. Finally, differentially methylated positions between boys and girls replicated very well by both platforms in newborns and older children. These findings are encouraging for application of combined data from EPIC and 450K platforms for birth cohorts and other population studies. These data in children corroborate recent comparisons of the two BeadChips in adults and in cancer cell lines. However, researchers should be cautious when characterizing individual CpG sites and consider independent methods for validation of significant hits.

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Section: Methodsmentioning

confidence: 99%

Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

et al. 2018

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“…In this context, the Infinium 450k array represents the most widely used platform and allows the methylation analysis of more than 450 000 cytosine residues in the human genome. The corresponding probes have been selected to cover both general and specific features that are commonly linked to epigenetic gene regulation (Bibikova et al ., 2011). …”

Section: Introductionmentioning

confidence: 99%

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

et al. 2016

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SummaryEpigenetic changes represent an attractive mechanism for understanding the phenotypic changes associated with human aging. Age‐related changes in DNA methylation at the genome scale have been termed ‘epigenetic drift’, but the defining features of this phenomenon remain to be established. Human epidermis represents an excellent model for understanding age‐related epigenetic changes because of its substantial cell‐type homogeneity and its well‐known age‐related phenotype. We have now generated and analyzed the currently largest set of human epidermis methylomes (N = 108) using array‐based profiling of 450 000 methylation marks in various age groups. Data analysis confirmed that age‐related methylation differences are locally restricted and characterized by relatively small effect sizes. Nevertheless, methylation data could be used to predict the chronological age of sample donors with high accuracy. We also identified discontinuous methylation changes as a novel feature of the aging methylome. Finally, our analysis uncovered an age‐related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks. Our findings thus define the loss of epigenetic regulatory fidelity as a key feature of the aging epigenome.

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“…The primary alternate approach to methylation analysis that does not use NGS is high density microarrays (Bibikova et al 2009;Bibikova et al 2011). These micorarrays are adaptations of SNP microarrays widely used in the genetics field, coupled with bisulfite conversion.…”

Section: Methylation Microarraysmentioning

confidence: 99%

Analysis of DNA modifications in aging research

et al. 2018

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As geroscience research extends into the role of epigenetics in aging and age-related disease, researchers are being confronted with unfamiliar molecular techniques and data analysis methods that can be difficult to integrate into their work. In this review, we focus on the analysis of DNA modifications, namely cytosine methylation and hydroxymethylation, through nextgeneration sequencing methods. While older techniques for modification analysis performed relative quantitation across regions of the genome or examined average genome levels, these analyses lack the desired specificity, rigor, and genomic coverage to firmly establish the nature of genomic methylation patterns and their response to aging. With recent methodological advances, such as whole genome bisulfite sequencing (WGBS), bisulfite oligonucleotide capture sequencing (BOCS), and bisulfite amplicon sequencing (BSAS), cytosine modifications can now be readily analyzed with base-specific, absolute quantitation at both cytosine-guanine dinucleotide (CG) and non-CG sites throughout the genome or within specific regions of interest by next-generation sequencing. Additional advances, such as oxidative bisulfite conversion to differentiate methylation from hydroxymethylation and analysis of limited input/single-cells, have great promise for continuing to expand epigenomic capabilities. This review provides a background on DNA modifications, the current state-of-theart for sequencing methods, bioinformatics tools for converting these large data sets into biological insights, and perspectives on future directions for the field.

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High density DNA methylation array with single CpG site resolution

Cited by 1,486 publications

References 42 publications

Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

Comparison of DNA methylation measured by Illumina 450K and EPIC BeadChips in blood of newborns and 14-year-old children

Reduced DNA methylation patterning and transcriptional connectivity define human skin aging

Analysis of DNA modifications in aging research

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