Evidence map›Paper›PMID 34663425›Full record

ArticleGenome biology2021

DNA methylation-calling tools for Oxford Nanopore sequencing: a survey and human epigenome-wide evaluation.

Yang Liu, Wojciech Rosikiewicz, Ziwei Pan, Nathaniel Jillette, Ping Wang, Aziz Taghbalout, Jonathan Foox, Christopher Mason, Martin Carroll, Albert Cheng and 1 more

Open access · goldAbstract readEvaluation Study
In one paragraph

Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed
16.8field-weighted citation impact, top 1% 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

153 citing papers in PubMed, 258 citations in OpenAlex.

  1. Trial
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  7. Fluorescent Analysis of KBiomolecules · 2026
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  16. EnDeep4mC predicts DNAGenome research · 2026
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  18. How to Unmask an Unknown: The Restriction-Modification SystemInternational journal of molecular sciences · 2026
    Article
  19. Review
  20. Article

93 more citing papers are in PubMed but not listed here.

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 5 institutions in 1 country.

Yang Liu *The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Wojciech Rosikiewicz *The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Ziwei Pan *The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Nathaniel JilletteThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Ping WangThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Aziz TaghbaloutThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Jonathan FooxDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Christopher MasonDepartment of Physiology and Biophysics, Weill Cornell Medicine, New York, NY, USA.
Martin CarrollDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Albert ChengThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Sheng LiThe Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. sheng.li@jax.org.ORCID http://orcid.org/0000-0002-9543-6274
Jackson Laboratory · USCornell University · USSt. Jude Children's Research Hospital · USUniversity of Connecticut · USUniversity of Pennsylvania · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Jeffrey Hsu-Min Chuang · 1985 to 2026
$61.9M
The Spatiotemporal Landscape of the Human Brain EpitranscriptomeR01MH117406 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI MASON, CHRISTOPHER EDWARD · 2018 to 2022
$3.3M
An Integrative Computational Framework for DNA Hydroxymethylation Data Mining and InterpretationR35GM133562 · NIGMS · JACKSON LABORATORY · PI LI, SHENG · 2019 to 2023
$2.4M
NCI NIH HHS P30 CA034196NIGMS NIH HHS R35 GM133562NIMH NIH HHS R01 MH117406
6 · The paper itself

Abstract

backgroundNanopore long-read sequencing technology greatly expands the capacity of long-range, single-molecule DNA-modification detection. A growing number of analytical tools have been developed to detect DNA methylation from nanopore sequencing reads. Here, we assess the performance of different methylation-calling tools to provide a systematic evaluation to guide researchers performing human epigenome-wide studies.

resultsWe compare seven analytic tools for detecting DNA methylation from nanopore long-read sequencing data generated from human natural DNA at a whole-genome scale. We evaluate the per-read and per-site performance of CpG methylation prediction across different genomic contexts, CpG site coverage, and computational resources consumed by each tool. The seven tools exhibit different performances across the evaluation criteria. We show that the methylation prediction at regions with discordant DNA methylation patterns, intergenic regions, low CG density regions, and repetitive regions show room for improvement across all tools. Furthermore, we demonstrate that 5hmC levels at least partly contribute to the discrepancy between bisulfite and nanopore sequencing. Lastly, we provide an online DNA methylation database ( https://nanome.jax.org ) to display the DNA methylation levels detected by nanopore sequencing and bisulfite sequencing data across different genomic contexts.

conclusionsOur study is the first systematic benchmark of computational methods for detection of mammalian whole-genome DNA modifications in nanopore sequencing. We provide a broad foundation for cross-platform standardization and an evaluation of analytical tools designed for genome-scale modified base detection using nanopore sequencing.

Indexed as

DNA MethylationEpigenomeNanopore SequencingSoftware5-MethylcytosineCpG IslandsGenome, HumanHumans5-MethylcytosineBase modificationDNA methylationLong-read sequencingMethylation callingNanopore sequencing

Identifiers

PMID34663425
PMCPMC8524990
OpenAlexW3205308293

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.