ArticleNature biotechnology2025
Simultaneous single-cell analysis of 5mC and 5hmC with SIMPLE-seq.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- Multi-omics-driven precision medicine.iMeta · 2026Review
- Simultaneous single-base resolution profiling of 5mC and 5hmC using BRIGHT-seq.National science review · 2026Article
- The molecular asynchrony of single cells.bioRxiv : the preprint server for biology · 2026Article
- HM-DyadCap - capture and mapping of 5-hydroxymethylcytosine/5-methylcytosine CpG dyads in mammalian DNA.Nucleic acids research · 2026Article
- Article
- DNA methylation meets lineage tracing: History, recent progress, and future directions.Quantitative biology (Beijing, China) · 2026Article
- Postnatal conversion of methylcytosine to hydroxymethylcytosine reconfigures the human neuronal epigenome.bioRxiv : the preprint server for biology · 2026Article
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- Cell type inference in cell-free nucleic acid liquid biopsy.Nature biotechnology · 2025Review
- Review
- KnowYourCG: Facilitating base-level sparse methylome interpretation.Science advances · 2025Article
- DNA methylation and machine learning: challenges and perspective toward enhanced clinical diagnostics.Clinical epigenetics · 2025Review
- A ternary-code DNA methylome atlas of mouse tissues.Genome biology · 2025Article
- Ternary-code DNA methylation dynamics: A new era for scalable mapping.Cell genomics · 2025Article
- Scalable screening of ternary-code DNA methylation dynamics associated with human traits.Cell genomics · 2025Article
- Artificial intelligence for comprehensive DNA methylation analysis: overview, challenges, and future directions.Briefings in bioinformatics · 2025Review
- Direct and bisulfite-free 5-methylcytosine and 5-hydroxymethylcytosine sequencing at single-cell resolution with scTAPS and scCAPS + .Genome biology · 2025Article
- Mild and ultrafast GLORI enables absolute quantification of mNature methods · 2025Article
- Review
- 5-Hydroxymethylcytosine signatures in circulating cell-free DNA as potential diagnostic markers for breast cancer.Biomarkers in medicine · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Dynamic 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) modifications to DNA regulate gene expression in a cell-type-specific manner and are associated with various biological processes, but the two modalities have not yet been measured simultaneously from the same genome at the single-cell level. Here we present SIMPLE-seq, a scalable, base resolution method for joint analysis of 5mC and 5hmC from thousands of single cells. Based on orthogonal labeling and recording of 'C-to-T' mutational signals from 5mC and 5hmC sites, SIMPLE-seq detects these two modifications from the same molecules in single cells and enables unbiased DNA methylation dynamics analysis of heterogeneous biological samples. We applied this method to mouse embryonic stem cells, human peripheral blood mononuclear cells and mouse brain to give joint epigenome maps at single-cell and single-molecule resolution. Integrated analysis of these two cytosine modifications reveals distinct epigenetic patterns associated with divergent regulatory programs in different cell types as well as cell states.
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Registered trials
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.