Fine mapping regulatory variants by characterizing native CpG methylation with nanopore long-read sequencing.

ABSTRACT: 5-Methylcytosine (5mC) is the most common DNA modification in the human genome. Bisulfite conversion combined with short-read sequencing captures this modification at single-nucleotide resolution but introduces PCR duplication bias and limits co-methylation analysis between distant cytosines. To resolve these limitations, we used nanopore long-read sequencing to profile human methylation and performed long-range co-methylation analysis with native DNA modification information. We analyzed the nanopore demo data in the adaptive sampling sequencing targeting the CpG islands and applied the linkage disequilibrium (LD) R² to identified methylation haplotype blocks (MHBs). We found that the cancer genome exhibited significantly smaller MHBs, higher CpG density, and a lower methylatio

SUBMITTER: Tian Y 

PROVIDER: S-EPMC12642126 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature