Genome skimming with nanopore sequencing precisely determines global and transposon DNA methylation in vertebrates

Abstract

Genome skimming is defined as low-pass sequencing below 0.05× coverage and is typically used for mitochondrial genome recovery and species identification. Long-read nanopore sequencers enable simultaneous reading of both DNA sequence and methylation and can multiplex samples for low-cost genome skimming. Here I present nanopore sequencing as a highly precise platform for global DNA methylation and transposon assessment. At coverage of just 0.001×, or 30 Mb of reads, accuracy is sub-1%. Biological and technical replicates validate high precision. Skimming 40 vertebrate species reveals conserved patterns of global methylation consistent with whole-genome bisulfite sequencing and an average mapping rate >97%. Genome size directly correlates to global DNA methylation, explaining 39% of its variance. Accurate SINE and LINE transposon methylation in both the mouse and primates can be obtained with just 0.0001× coverage, or 3 Mb of reads. Sample multiplexing, field portability, and the low price of this instrument combine to make genome skimming for DNA methylation an accessible method for epigenetic assessment from ecology to epidemiology and for low-resource groups.