Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns

Tang, Binhua; Zhou, Yufan; Wang, Chiou Miin; Huang, Tim H.M.; Jin, Victor X.

doi:10.1038/s41598-017-03837-z

Cited by 21 publications

(22 citation statements)

References 47 publications

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“…All report a high overall correlation between DNA methylation of the same samples measured using different methods. Not all of these studies commented on individual CpG site correlation; however, manual inspection of the correlation scatter plots reveals that a subset of CpGs shows large differences in methylation values between the platforms being compared [1,[15][16][17][18]. Altogether, these studies demonstrate that some CpGs reproduce poorly, regardless of sample type or method used.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage

et al. 2019

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DNA methylation of CpG sites is commonly measured using Illumina Infinium BeadChip platforms. The Infinium MethylationEPIC array has replaced the Infinium Methylation450K array. The two arrays use the same technology, with the EPIC array assaying almost double the number of sites than the 450K array. In this study, we compare DNA methylation values of shared CpGs of the same human cartilage samples assayed using both platforms. DNA methylation was measured in 21 human cartilage samples using the both 450K and EPIC arrays. Additional matched 450K and EPIC data in whole tumour and whole blood were downloaded from GEO GSE92580 and GSE86833, respectively. Data were processed using the Bioconductor package Minfi. DNA methylation of six CpG sites was validated for the same 21 cartilage samples by pyrosequencing. In cartilage samples, overall sample correlations of methylation values between arrays were high (Pearson's r > 0.96). However, 50.5% of CpG sites showed poor correlation (r < 0.2) between arrays. Sites with limited variance and with either very high or very low methylation levels in cartilage exhibited lower correlation values, corroborating prior studies in whole blood. Bisulphite pyrosequencing did not highlight one array as generating more accurate methylation values. For a specific CpG site, the array methylation correlation coefficient differed between cartilage, tumour, and whole blood, reflecting the difference in methylation variance between cell types. Researchers should be cautious when analysing methylation of CpG sites that show low methylation variance within the cell type of interest, regardless of the method used to assay methylation. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage

et al. 2019

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“…49 Epigenetic DNA modifications occur in prokaryotic and eukaryotic cells. 50,51 However, little is known about the role of such nucleic acid changes in controlling spurious transcription initiation. To date, the best characterised consequences are those identified in mouse embryonic stem cells, 52 where intragenic methylation of CpG dinucleotides within the body of genes is required to prevent intragenic transcription initiation by RNA polymerase II.…”

Section: Inhibition Of Spurious Transcription Initiationmentioning

confidence: 99%

Spurious transcription and its impact on cell function

Wade

Grainger

2017

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Most RNA polymerases can initiate transcription from diverse DNA template sequences with relatively few outright sequence restraints. Recent reports have demonstrated that failure to subdue the promiscuity of RNA polymerase in vivo can severely impede cell function. This phenomenon appears common to all cell types with undesirable effects ranging from growth inhibition in prokaryotes to cancer in higher organisms. Here we discuss similarities and differences in strategies employed by cells to minimise spurious transcription across life's domains.

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“…Past studies examining the similarity of measurements in 450K and pyrosequencing in cell lines and brain tissue [9,14] have also observed that some CpG sites do not reproduce. Moreover, comparisons of 450K to whole genome bisulfite sequencing showed the same conclusions [1,15,16] as did reduced representation bisulfite sequencing [17,18]. Multiple published manuscripts have described the correlation of CpG sites measured using different methods.…”

Section: Discussionmentioning

confidence: 71%

“…All report a high overall correlation between DNA methylation of the same samples measured using different methods. Not all of these studies commented on individual CpG site correlation, however, manual inspection of the correlation scatter plots reveal that a subset of CpGs show large differences in methylation values between the platforms being compared [1,[15][16][17][18]. Altogether, these studies demonstrate that some CpGs reproduce poorly, regardless of sample type or method used.…”

Section: Discussionmentioning

confidence: 99%

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage

Cheung

Burgers

Young

et al. 2019

Preprint

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BackgroundDNA methylation of CpG sites is commonly measured using Illumina Infinium BeadChip platforms. The Infinium MethylationEPIC array has replaced the Infinium Methylation450K array. The two arrays use the same technology, with the EPIC array assaying 865859 CpG sites, almost double the number of sites present on the 450K array. In this study, we compare DNA methylation values of shared CpGs of the same human cartilage samples assayed using both platforms. Methods DNA methylation was measured in 21 human cartilage samples using the Illumina InfiniumMethylation450K BeadChip and the Infinium methylationEPIC array. Additional matched 450K and EPIC data in whole tumour and whole blood were downloaded from GEO GSE92580 and GSE86833 respectively. Data were processed using the Bioconductor package Minfi. Additionally, DNA methylation of six CpG sites was validated for the same 21 cartilage samples by use of pyrosequencing. ResultsIn cartilage samples, overall sample correlations between methylation values generated by the two arrays were high (Pearson correlation coefficient r > 0.96). However, 50.5% of CpG sites showed poor correlation (r < 0.2) between arrays. Sites with limited variance and with either very high or very low methylation levels in cartilage exhibited lower correlation values, corroborating prior studies in whole blood. Bisulfite pyrosequencing did not highlight one array as generating more accurate methylation values that the other. For a specific CpG site, the array methylation correlation coefficient differed between cartilage, tumour and whole blood, reflecting the difference in methylation variance between cell types. These patterns can be observed across different tissues with different CpG site variances. When performing differential methylation analysis, the mean probe correlation co-efficient increased with increasing Δβ threshold used. ConclusionCpG sites with low variability within a tissue showed poor reproducibility between arrays.However, variance and thus reproducibility differs across different tissue types. Therefore, researchers should be cautious when analysing methylation of CpG sites that show low methylation variance within the cell type of interest, regardless of platform or method used to assay methylation.

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Integration of DNA methylation and gene transcription across nineteen cell types reveals cell type-specific and genomic region-dependent regulatory patterns

Cited by 21 publications

References 47 publications

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage

Spurious transcription and its impact on cell function

Correlation of Infinium HumanMethylation450K and MethylationEPIC BeadChip arrays in cartilage

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