Long-read nanopore sequencing maps allele-specific DNA methylation at regulatory variants in prostate tissue

Noncoding variants in the genome can influence gene expression by altering the epigenetic regulation of nearby sequences, but characterising these effects has historically required separate assays for genetic variation and DNA methylation. Long-read nanopore sequencing offers a route to measuring both simultaneously on single DNA molecules, as the technology detects native base modifications — including 5-methylcytosine — alongside sequence variation.

A preprint posted to bioRxiv introduces nanoASM, a framework applying whole-genome nanopore sequencing to normal and tumour prostate tissue to characterise allele-specific methylation (ASM) associated with noncoding genetic variants. Genome-wide analysis identified extensive cancer-associated differentially methylated regions, with hypermethylated regions enriched at gene promoters in tumour tissue. The allele-specific analysis links specific germline variants to local methylation differences, providing a functional annotation layer for regulatory noncoding variants that are difficult to interpret through sequence alone.

The approach adds resolution to how common germline variants may modulate cancer-relevant gene regulation without altering protein-coding sequence. The authors suggest nanoASM provides a scalable framework for functional annotation of noncoding variants across tissues and disease contexts.

This is a preprint and has not yet been peer-reviewed. The work is of primary interest to cancer genomics researchers, epigenomics specialists, and those working on variant interpretation methodology.