Cited by 324Nanopore and Nanochannel Transport StudiesEpigenetics and DNA MethylationDNA and Nucleic Acid Chemistry

Detection and mapping of 5-methylcytosine and 5-hydroxymethylcytosine with nanopore MspA

Open access
Laszlo, Andrew H., Derrington, Ian M., Brinkerhoff, Henry, Langford, Kyle W., Nova, Ian C., Samson, Jenny Mae, Bartlett, Joshua J., Pavlenok, Mikhail +1 more·2013·Proceedings of the National Academy of Sciences

Abstract

Significance: Cells attach a methyl group (—CH 3 ) to certain cytosines in DNA to control gene expression. These methylation patterns change over time and can be related to cell differentiation and diseases such as cancer. Existing methylation detection techniques are not ideal for clinical use. We pulled single-stranded DNA molecules through the biological pore MspA and found that ion currents passing through the pore reveal the methylation sites with high confidence. Hydroxymethylation, which differs from methylation by only one oxygen atom, also produces distinct signals. This technique can be developed into a research tool and may ultimately lead to clinical tests.

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Crossref · 10.1073/pnas.1310240110

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  • Nanopore sequencing is able to detect 5-hmC, which is not adequately covered by traditional array/bisulfite sequencing methods.

    “In addition, nanopore sequencing is able to detect 5-hmC (301), which is not adequately covered by traditional array/bisulfite sequencing methods.”

    From Epigenetic Modifications in Stress Response Genes Associated With Childhood Trauma (2019) · cites this paper as [301]

    The Discussion reports distinct nanopore current signatures for 5-hmC, supporting its detection. The paper also says conventional bisulfite sequencing cannot distinguish 5-hmC from 5-mC, though oxidative bisulfite sequencing can do so with substantial sample loss. It does not assess traditional array methods, so that part of the comparison is unsupported. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Research works printed but not linked: 1

  1. Laird PW (2010) Principles and challenges of genomewide DNA methylation analysis. Nat Rev Genet 11(3):191-203.

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Authors
Laszlo, A. H., Derrington, I. M., Brinkerhoff, H., Langford, K. W., Nova, I. C., Samson, J. M., Bartlett, J. J., Pavlenok, M., & Gundlach, J. H.
Affiliations
  • University of Washington (US)
  • University of Alabama at Birmingham (US)
Venue
Proceedings of the National Academy of Sciences
Published
2013-10-28
Volume
110
Issue
47
Pages
18904-18909
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2073105380
Cited by
321
References
38
Citations by year
2026: 17 · 2025: 21 · 2024: 32 · 2023: 19 · 2022: 26 · 2021: 38 · 2020: 15 · 2019: 21 · 2018: 21 · 2017: 27 · 2016: 30 · 2015: 33 · 2014: 19 · 2013: 2
FWCI
15.46
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Human Genome Research Institute (R01HG006321, R01HG005115)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Nanopore and Nanochannel Transport Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
Keywords
5-methylcytosine, 5-hydroxymethylcytosine, DNA methylation, DNA hydroxymethylation, nanopore sequencing, single-molecule detection, epigenetic modifications, ionic currents, phi29 DNA polymerase, DNA strand passage
MeSH terms
Bayes Theorem, Cytosine, Models, Molecular, Molecular Structure, Porins, DNA Methylation, 5-Methylcytosine, Epigenomics, Nanopores

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