A Statistical Method for Observing Personal Diploid Methylomes and Transcriptomes with Single-Molecule Real-Time Sequencing

Genes
Yuta SuzukiShinichi Morishita

Abstract

We address the problem of observing personal diploid methylomes, CpG methylome pairs of homologous chromosomes that are distinguishable with respect to phased heterozygous variants (PHVs), which is challenging due to scarcity of PHVs in personal genomes. Single molecule real-time (SMRT) sequencing is promising as it outputs long reads with CpG methylation information, but a serious concern is whether reliable PHVs are available in erroneous SMRT reads with an error rate of ∼15%. To overcome the issue, we propose a statistical model that reduces the error rate of phasing CpG site to 1%, thereby calling CpG hypomethylation in each haplotype with >90% precision and sensitivity. Using our statistical model, we examined GNAS complex locus known for a combination of maternally, paternally, or biallelically expressed isoforms, and observed allele-specific methylation pattern almost perfectly reflecting their respective allele-specific expression status, demonstrating the merit of elucidating comprehensive personal diploid methylomes and transcriptomes.

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Citations

Jan 10, 2019·Genes·Matthew S Hestand, Adam Ameur

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Datasets Mentioned

BETA
GM24385

Methods Mentioned

BETA
immunoprecipitation
RNA-seq

Software Mentioned

ASE
AgIn
GMAP aligner
BWA aligner
GENCODE
IDP
ChromHMM
Hisat2 aligner
UCSC Genome Browser
Segway

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