ArticleProceedings of the National Academy of Sciences of the United States of America2021
Genome-wide detection of cytosine methylation by single molecule real-time sequencing.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 138 citations in OpenAlex.
- Unveiling centromeric retrotransposon dynamics through a high-quality rye genome assembly.Nature communications · 2026Article
- Methylation Dynamics inMicroorganisms · 2026Article
- Long-read sequencing technologies and bioinformatics: a new perspective for decoding DNA methylation modifications.Journal of translational medicine · 2026Review
- Characterizing cytosine methylation of polymorphic transposable element insertions using the human pangenome resources.Genome research · 2026Article
- ac4C modification sites prediction in human mRNA: a complete review.Briefings in bioinformatics · 2026Review
- Methylation array signals are predictive of chronological age without bisulfite conversion.GeroScience · 2026Article
- Z-Calling: a tool for A/Z (2,6-diaminopurine) base calling and dZ-DNA detection using PacBio HiFi reads.Communications biology · 2026Article
- Naturally-occurring DNA fragment termini correlate with methylation at CpG sites in hair and blood plasma cell-free DNA.BMC genomics · 2026Article
- Long-read sequencing for cancer liquid biopsy: advancing precision oncology.Frontiers in oncology · 2026Review
- Early-stage lung adenocarcinoma affects DNA methylation and gene expression in adjacent tissues.EMBO reports · 2025Article
- Advancements in DNA methylation technologies and their application in cancer diagnosis.Epigenetics · 2025Review
- Exploring cattle structural variation in the era of long reads, pangenome graphs, and near-complete assemblies.Journal of animal science and biotechnology · 2025Review
- Non-CG DNA methylation in animal genomes.Nature genetics · 2025Review
- Computational analysis of DNA methylation from long-read sequencing.Nature reviews. Genetics · 2025Review
- Integrating multi-omics and machine learning for disease resistance prediction in legumes.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2025Review
- Molecular insights and clinical implications of DNA methylation in sepsis-associated acute kidney injury: a narrative review.BMC nephrology · 2025Review
- Long and Accurate: How HiFi Sequencing is Transforming Genomics.Genomics, proteomics & bioinformatics · 2025Review
- Unraveling the hidden complexity of cancer through long-read sequencing.Genome research · 2025Review
- Transformer-based deep learning for accurate detection of multiple base modifications using single molecule real-time sequencing.Communications biology · 2025Article
- Redox regulation: mechanisms, biology and therapeutic targets in diseases.Signal transduction and targeted therapy · 2025Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-Methylcytosine (5mC) is an important type of epigenetic modification. Bisulfite sequencing (BS-seq) has limitations, such as severe DNA degradation. Using single molecule real-time sequencing, we developed a methodology to directly examine 5mC. This approach holistically examined kinetic signals of a DNA polymerase (including interpulse duration and pulse width) and sequence context for every nucleotide within a measurement window, termed the holistic kinetic (HK) model. The measurement window of each analyzed double-stranded DNA molecule comprised 21 nucleotides with a cytosine in a CpG site in the center. We used amplified DNA (unmethylated) and M.SssI-treated DNA (methylated) (M.SssI being a CpG methyltransferase) to train a convolutional neural network. The area under the curve for differentiating methylation states using such samples was up to 0.97. The sensitivity and specificity for genome-wide 5mC detection at single-base resolution reached 90% and 94%, respectively. The HK model was then tested on human-mouse hybrid fragments in which each member of the hybrid had a different methylation status. The model was also tested on human genomic DNA molecules extracted from various biological samples, such as buffy coat, placental, and tumoral tissues. The overall methylation levels deduced by the HK model were well correlated with those by BS-seq (
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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.