Impact of ex-zd bit-reduction on ONT DNA methylation profiling. (A) Bar chart shows the correlation of 5mC methylation frequencies at global CpG sites recorded with whole-genome bisulfite sequencing (WGBS) versus ONT methylation profiling on a matched sample (HG002). ONT methylation profiling was performed with either Dorado (light gray) versus Guppy (dark gray) software and SUP (left) versus HAC (right) models on the same raw signal data set (HG002-Prom5K Chr 22 subset) (see Supplemental Table S1) encoded with a decreasing number of bits (native 11-bit down to 5-bit). (B) Density scatterplots compare global 5mC profiles from native 11-bit data and bit-reduced 8-bit data to WGBS data, as per the above comparisons. (C) Density scatterplots show 5mC methylation frequencies for individual basecalled reads, that is, the fraction of CpG bases within a given read that are called as being methylated. The left plot compares native 11-bit data versus bit-reduced 8-bit data, both basecalled with Dorado SUP model. The right plot shows native 11-bit data basecalled with Guppy versus Dorado software, using the same SUP methcalling model.
