Using long-read sequencing to detect imprinted DNA methylation

Nucleic Acids Research
Scott GiganteMatthew E Ritchie

Abstract

Systematic variation in the methylation of cytosines at CpG sites plays a critical role in early development of humans and other mammals. Of particular interest are regions of differential methylation between parental alleles, as these often dictate monoallelic gene expression, resulting in parent of origin specific control of the embryonic transcriptome and subsequent development, in a phenomenon known as genomic imprinting. Using long-read nanopore sequencing we show that, with an average genomic coverage of ∼10, it is possible to determine both the level of methylation of CpG sites and the haplotype from which each read arises. The long-read property is exploited to characterize, using novel methods, both methylation and haplotype for reads that have reduced basecalling precision compared to Sanger sequencing. We validate the analysis both through comparison of nanopore-derived methylation patterns with those from Reduced Representation Bisulfite Sequencing data and through comparison with previously reported data. Our analysis successfully identifies known imprinting control regions (ICRs) as well as some novel differentially methylated regions which, due to their proximity to hitherto unknown monoallelically expressed gene...Continue Reading

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Citations

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Datasets Mentioned

BETA
AC158554.1
ERP109201

Methods Mentioned

BETA
Methyl-Seq
RRBS
RNA-seq
PCR

Software Mentioned

ggbio
MinION
Tombo
mCaller
Ensembl
rtracklayer
signalAlign
BWA
GenomicRanges
MEM

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