Evidence map›Paper›PMID 29222086›Full record

ArticleGenome research2018

Genome-wide DNA methylation profiling using the methylation-dependent restriction enzyme LpnPI.

Ruben Boers, Joachim Boers, Bas de Hoon, Christel Kockx, Zeliha Ozgur, Anco Molijn, Wilfred van IJcken, Joop Laven, Joost Gribnau

Abstract read
In one paragraph

Article in Genome research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Ruben BoersDepartment of Developmental Biology, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
Joachim BoersDepartment of Developmental Biology, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
Bas de HoonDepartment of Developmental Biology, Erasmus MC, 3015 CN Rotterdam, the Netherlands.
Christel KockxCentre for Biomics, Erasmus MC, 3015 CE Rotterdam, the Netherlands.
Zeliha OzgurCentre for Biomics, Erasmus MC, 3015 CE Rotterdam, the Netherlands.
Anco MolijnDelft Diagnostic Laboratories, 2288 ER, Rijswijk, the Netherlands.
Wilfred van IJckenCentre for Biomics, Erasmus MC, 3015 CE Rotterdam, the Netherlands.
Joop LavenDepartment of Obstetrics and Gynaecology, Erasmus MC, 3015 CE Rotterdam, the Netherlands.
Joost GribnauDepartment of Developmental Biology, Erasmus MC, 3015 CN Rotterdam, the Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA methylation is a well-known epigenetic modification that plays a crucial role in gene regulation, but genome-wide analysis of DNA methylation remains technically challenging and costly. DNA methylation-dependent restriction enzymes can be used to restrict CpG methylation analysis to methylated regions of the genome only, which significantly reduces the required sequencing depth and simplifies subsequent bioinformatics analysis. Unfortunately, this approach has been hampered by complete digestion of DNA in CpG methylation-dense regions, resulting in fragments that are too small for accurate mapping. Here, we show that the activity of DNA methylation-dependent enzyme, LpnPI, is blocked by a fragment size smaller than 32 bp. This unique property prevents complete digestion of methylation-dense DNA and allows accurate genome-wide analysis of CpG methylation at single-nucleotide resolution. Methylated DNA sequencing (MeD-seq) of LpnPI digested fragments revealed highly reproducible genome-wide CpG methylation profiles for >50% of all potentially methylated CpGs, at a sequencing depth less than one-tenth required for whole-genome bisulfite sequencing (WGBS). MeD-seq identified a high number of patient and tissue-specific differential methylated regions (DMRs) and revealed that patient-specific DMRs observed in both blood and buccal samples predict DNA methylation in other tissues and organs. We also observed highly variable DNA methylation at gene promoters on the inactive X Chromosome, indicating tissue-specific and interpatient-specific escape of X Chromosome inactivation. These findings highlight the potential of MeD-seq for high-throughput epigenetic profiling.

Indexed as

Chromosomes, Human, XCpG IslandsEpigenesis, GeneticGenome-Wide Association StudyX Chromosome InactivationDeoxyribonuclease IDNA MethylationFemaleHumansDeoxyribonuclease I

Identifiers

PMID29222086
PMCPMC5749185

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.