Evidence map›Paper›PMID 20453866›Full record

ArticleNature methods2010

Direct detection of DNA methylation during single-molecule, real-time sequencing.

Benjamin A Flusberg, Dale R Webster, Jessica H Lee, Kevin J Travers, Eric C Olivares, Tyson A Clark, Jonas Korlach, Stephen W Turner

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 726 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
726citing papers in PubMed, 2 pooled it
37.2field-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

726 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,474 citations in OpenAlex.

  1. Pooled it
  2. [Advances in the Application of Forensic Microbiome Analysis in Tissue Source Inference].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025
    Pooled it
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  18. How Genomic and Structural Context Could Shape JAK-STAT Variant Pathogenicity.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2026
    Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Benjamin A FlusbergPacific Biosciences, Menlo Park, California, USA.
Dale R Webster
Jessica H Lee
Kevin J Travers
Eric C Olivares
Tyson A Clark
Jonas Korlach
Stephen W Turner
Pacific Biosciences (United States) · US

Funding

Direct Single Base-Pair Real-Time DNA Methylation SequencingRC2HG005618 · NHGRI · PACIFIC BIOSCIENCES OF CALIFORNIA, INC. · PI TURNER, STEPHEN WHITFIELD · 2009 to 2010
$1.2M
NHGRI NIH HHS 1RC2HG005618-01NHGRI NIH HHS RC2 HG005618
6 · The paper itself

Abstract

We describe the direct detection of DNA methylation, without bisulfite conversion, through single-molecule, real-time (SMRT) sequencing. In SMRT sequencing, DNA polymerases catalyze the incorporation of fluorescently labeled nucleotides into complementary nucleic acid strands. The arrival times and durations of the resulting fluorescence pulses yield information about polymerase kinetics and allow direct detection of modified nucleotides in the DNA template, including N6-methyladenine, 5-methylcytosine and 5-hydroxymethylcytosine. Measurement of polymerase kinetics is an intrinsic part of SMRT sequencing and does not adversely affect determination of primary DNA sequence. The various modifications affect polymerase kinetics differently, allowing discrimination between them. We used these kinetic signatures to identify adenine methylation in genomic samples and found that, in combination with circular consensus sequencing, they can enable single-molecule identification of epigenetic modifications with base-pair resolution. This method is amenable to long read lengths and will likely enable mapping of methylation patterns in even highly repetitive genomic regions.

Indexed as

DNA MethylationDNA-Directed DNA PolymeraseEscherichia coliKineticsPrincipal Component AnalysisSequence Analysis, DNADNA-Directed DNA Polymerase

Identifiers

PMID20453866
PMCPMC2879396
OpenAlexW1984783889

What OpenQuestion holds

Textmetadata
LicenceTDM
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.