MethPhaser: methylation-based long-read haplotype phasing of human genomes

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dc.citation.articleNumber5327en_US
dc.citation.journalTitleNature Communicationsen_US
dc.citation.volumeNumber15en_US
dc.contributor.authorFu, Yileien_US
dc.contributor.authorAganezov, Sergeyen_US
dc.contributor.authorMahmoud, Medhaten_US
dc.contributor.authorBeaulaurier, Johnen_US
dc.contributor.authorJuul, Sisselen_US
dc.contributor.authorTreangen, Todd J.en_US
dc.contributor.authorSedlazeck, Fritz J.en_US
dc.date.accessioned2024-08-22T15:28:50Zen_US
dc.date.available2024-08-22T15:28:50Zen_US
dc.date.issued2024en_US
dc.description.abstractThe assignment of variants across haplotypes, phasing, is crucial for predicting the consequences, interaction, and inheritance of mutations and is a key step in improving our understanding of phenotype and disease. However, phasing is limited by read length and stretches of homozygosity along the genome. To overcome this limitation, we designed MethPhaser, a method that utilizes methylation signals from Oxford Nanopore Technologies to extend Single Nucleotide Variation (SNV)-based phasing. We demonstrate that haplotype-specific methylations extensively exist in Human genomes and the advent of long-read technologies enabled direct report of methylation signals. For ONT R9 and R10 cell line data, we increase the phase length N50 by 78%-151% at a phasing accuracy of 83.4-98.7% To assess the impact of tissue purity and random methylation signals due to inactivation, we also applied MethPhaser on blood samples from 4 patients, still showing improvements over SNV-only phasing. MethPhaser further improves phasing across HLA and multiple other medically relevant genes, improving our understanding of how mutations interact across multiple phenotypes. The concept of MethPhaser can also be extended to non-human diploid genomes. MethPhaser is available at https://github.com/treangenlab/methphaser.en_US
dc.identifier.citationFu, Y., Aganezov, S., Mahmoud, M., Beaulaurier, J., Juul, S., Treangen, T. J., & Sedlazeck, F. J. (2024). MethPhaser: Methylation-based long-read haplotype phasing of human genomes. Nature Communications, 15(1), 5327. https://doi.org/10.1038/s41467-024-49588-0en_US
dc.identifier.digitals41467-024-49588-0en_US
dc.identifier.doihttps://doi.org/10.1038/s41467-024-49588-0en_US
dc.identifier.urihttps://hdl.handle.net/1911/117702en_US
dc.language.isoengen_US
dc.publisherSpringer Natureen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license.  Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleMethPhaser: methylation-based long-read haplotype phasing of human genomesen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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