London Calling 2023: MethPhaser: automated methylation-based haplotype phasing of human genomes with Oxford Nanopore sequencing

Long-read sequencing was declared the method of the year in 2022, and indeed, has fully arrived on the computational biology scene. Specifically, Oxford Nanopore sequencing technology has enabled computational approaches to assemble accurate and complete human genome haplotypes, while providing unprecedented methylation profiling. Nevertheless, homozygous regions and variability in read lengths limit traditional single-nucleotide polymorphism (SNP)-based haplotype phasing methods. To address this, we developed MethPhaser, a computational method for automated methylation-based haplotype phasing of  the human genome. MethPhaser is the first in the long-read era to utilize SNP and methylation signals for human genome phasing. We show MethPhaser improves upon widely used SNP-based human genome  phasing approaches by bridging the SNP-phased blocks to resolve the ambiguity in homozygous regions. MethPhaser is also able to rescue previously un-haplotagged reads from SNP-based methods. We will conclude with future directions and the next steps. MethPhaser is available at: https://gitlab.com/treangenlab/MethPhaser