RICO enables integrated analysis of ribosomal DNA copy number and methylation from nanopore long-read sequencing

RICO enables integrated estimation of ribosomal DNA copy number and methylation from Oxford Nanopore long reads, accurately quantifying rDNA CN and capturing ~40% CN changes in Atrx-knockout mouse embryonic stem cells.

• Why it matters: rDNA copy number is clinically relevant but hard to measure because tandem repeats are repetitive and GC-rich, and methylation is often analyzed separately rather than jointly.
• What they did: RICO uses long reads spanning entire rDNA repeats, maps them to an rDNA-augmented reference genome, and normalizes coverage with a single-copy gene panel to estimate rDNA CN and methylation.
• The result: It yields accurate, reproducible rDNA CN in simulated and human samples, matches short-read and PCR-based measurements, reproduces a ~40% reduction in Atrx-knockout cells, detects increased total and active rDNA CN in MYC-driven lymphoma, and links higher total rDNA CN to higher fractions of highly methylated copies in independent human cohorts.

AI summary of the abstract · may contain errors · not medical advice · read the paper.