Accurate targeted long-read DNA methylation and hydroxymethylation sequencing with TAPS
Yibin Liu, Jingfei Cheng, Paulina Siejka-Zielińska, Carika Weldon, Hannah Roberts, Maria Lopopolo, Andrea Magrì, Valentina D’Arienzo, James Michael Harris, Jane A. McKeating, Chun‐Xiao Song
Abstract
We present long-read Tet-assisted pyridine borane sequencing (lrTAPS) for targeted base-resolution sequencing of DNA methylation and hydroxymethylation in regions up to 10 kb from nanogram-level input. Compatible with both Oxford Nanopore and PacBio Single-Molecule Real-Time (SMRT) sequencing, lrTAPS detects methylation with accuracy comparable to short-read Illumina sequencing but with long-range epigenetic phasing. We applied lrTAPS to sequence difficult-to-map regions in mouse embryonic stem cells and to identify distinct methylation events in the integrated hepatitis B virus genome.