Evidence map›Paper›PMID 34147133›Full record

ArticleEpigenetics & chromatin2021

Evaluation of whole-genome DNA methylation sequencing library preparation protocols.

Jacob Morrison, Julie M Koeman, Benjamin K Johnson, Kelly K Foy, Ian Beddows, Wanding Zhou, David W Chesla, Larissa L Rossell, Emily J Siegwald, Marie Adams and 1 more

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
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

34 citing papers in PubMed, 91 citations in OpenAlex.

  1. Article
  2. Article
  3. Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026
    Review
  4. Laser Capture Microdissection Followed by DNA Methylation Profiling.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
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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

11 authors at 3 institutions in 1 country.

Jacob MorrisonDepartment of Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.
Julie M KoemanGenomics Core, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.
Benjamin K JohnsonDepartment of Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.
Kelly K FoyDepartment of Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.
Ian BeddowsDepartment of Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA.
Wanding ZhouCenter for Computational and Genomic Medicine, The Children's Hospital of Philadelphia, 3501 Civic Center Boulevard, Philadelphia, PA, 19104, USA.
David W CheslaSpectrum Health Office of Research and Education, Spectrum Health System, 15 Michigan Street NE, Grand Rapids, MI, 49503, USA.
Larissa L RossellSpectrum Health Office of Research and Education, Spectrum Health System, 15 Michigan Street NE, Grand Rapids, MI, 49503, USA.
Emily J SiegwaldSpectrum Health Office of Research and Education, Spectrum Health System, 15 Michigan Street NE, Grand Rapids, MI, 49503, USA.
Marie Adams *Genomics Core, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA. marie.adams@vai.org.
Hui Shen *Department of Epigenetics, Van Andel Research Institute, 333 Bostwick Avenue NE, Grand Rapids, MI, 49503, USA. hui.shen@vai.org.ORCID 0000-0001-9767-4084
Van Andel Institute · USSpectrum Health · USChildren's Hospital of Philadelphia · US

Funding

High-throughput Epigenomic Mapping of Regulatory Elements in Ovarian Cancer at Basepair ResolutionR37CA230748 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI SHEN, HUI · 2018 to 2024
$3.4M
NCI NIH HHS R37 CA230748
6 · The paper itself

Abstract

backgroundWith rapidly dropping sequencing cost, the popularity of whole-genome DNA methylation sequencing has been on the rise. Multiple library preparation protocols currently exist. We have performed 22 whole-genome DNA methylation sequencing experiments on snap frozen human samples, and extensively benchmarked common library preparation protocols for whole-genome DNA methylation sequencing, including three traditional bisulfite-based protocols and a new enzyme-based protocol. In addition, different input DNA quantities were compared for two kits compatible with a reduced starting quantity. In addition, we also present bioinformatic analysis pipelines for sequencing data from each of these library types.

resultsAn assortment of metrics were collected for each kit, including raw read statistics, library quality and uniformity metrics, cytosine retention, and CpG beta value consistency between technical replicates. Overall, the NEBNext Enzymatic Methyl-seq and Swift Accel-NGS Methyl-Seq kits performed quantitatively better than the other two protocols. In addition, the NEB and Swift kits performed well at low-input amounts, validating their utility in applications where DNA is the limiting factor.

resultsThe NEBNext Enzymatic Methyl-seq kit appeared to be the best option for whole-genome DNA methylation sequencing of high-quality DNA, closely followed by the Swift kit, which potentially works better for degraded samples. Further, a general bioinformatic pipeline is applicable across the four protocols, with the exception of extra trimming needed for the Swift Biosciences's Accel-NGS Methyl-Seq protocol to remove the Adaptase sequence.

Indexed as

CytosineDNA MethylationGene LibraryHumansSequence Analysis, DNAWhole Genome SequencingCytosineDNA methylationEnzymatic methylation sequencingEpigeneticsFallopian tubeWhole-genome bisulfite sequencing

Identifiers

PMID34147133
PMCPMC8214260
OpenAlexW3134869800

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.