Eilis Hannon from the University of Exeter in the UK presented at the Nanopore Community Meeting 2021 about “Evaluation of nanopore sequencing for epigenetic epidemiology: a comparison with DNA methylation microarrays.” Hannon explained that there is increasing interest in epigenome and human population studies. Sodium bisulfite treatment was the most common approach for profiling along with microarrays. Now, third generation sequencing technologies help detect modified bases. However, Hannon noted that the viability for epigenetic epidemiology is not well studied. They aimed to study differentially modified positions associated with tobacco smoking. Two samples were sequenced on two MinION flow cells. Hannon and team used CRISPR to enrich for coverage within targeted regions. With a mean distance between guide RNA of 15 kb, this method was used successfully to sequence targets of interest. They found strong concordance between ONT and Illumina EPIC arrays results. They then assessed differential methylation detected from Nanopore reads. In general, the Nanopore data was consistent with the EPIC array. Hannon and team also analyzed the minimum number of reads to detect differences. In summary, they used CRISPR to enrich for targeted regions and detected DNA methylation signals, in alignment with Illumina EPIC approaches. This approach combines CRISPR-mediated enrichment with modified base detection.
