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DMN-seq enriches DNA hypomethylated regions for biomarker discovery using 5-methylcytosine glycosylase.

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Genome biology 2026 Vol.27(1)
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PubMed DOI PMC

Wang Y, Li Y, Ye C, Irkliyenko I, Gao L, Bissonnette M, Dai Q, Tang W, He C

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Various methods have been developed for 5-methylcytosine (5mC) sequencing; however, effective ways to enrich hypomethylated DNA regions have been limited.

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BibTeX ↓ RIS ↓
APA Wang Y, Li Y, et al. (2026). DMN-seq enriches DNA hypomethylated regions for biomarker discovery using 5-methylcytosine glycosylase.. Genome biology, 27(1). https://doi.org/10.1186/s13059-026-03991-6
MLA Wang Y, et al.. "DMN-seq enriches DNA hypomethylated regions for biomarker discovery using 5-methylcytosine glycosylase.." Genome biology, vol. 27, no. 1, 2026.
PMID 41673887
DOI 10.1186/s13059-026-03991-6

Abstract

Various methods have been developed for 5-methylcytosine (5mC) sequencing; however, effective ways to enrich hypomethylated DNA regions have been limited. Here, we describe the DEMETER-assisted 5-Methylcytosine Nicking sequencing (DMN-seq) utilizing 5mC-specific glycosylase DEMETER to nick DNA at 5mC sites, enabling 5mC detection at the single-base resolution. Leveraging this nicking activity to deplete hypermethylated sites, we adapt DMN-seq to preferentially enrich and investigate hypomethylated regions in colorectal cancer samples. When applied to cell-free DNA as low as 0.1 ng, DMN-seq significantly expands the scope of cancer biomarkers by capturing hypomethylated regions, with high sensitivity and reproducibility even in low-input clinical samples.

MeSH Terms

Humans; DNA Methylation; Biomarkers, Tumor; 5-Methylcytosine; Colorectal Neoplasms; Sequence Analysis, DNA; High-Throughput Nucleotide Sequencing; DNA Glycosylases

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