Discovering multiple types of DNA methylation from bacteria and microbiome using nanopore sequencing

Alan Tourancheau, Edward A. Mead, Xue Song Zhang, Gang Fang

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Bacterial DNA methylation occurs at diverse sequence contexts and plays important functional roles in cellular defense and gene regulation. Existing methods for detecting DNA modification from nanopore sequencing data do not effectively support de novo study of unknown bacterial methylomes. In this work, we observed that a nanopore sequencing signal displays complex heterogeneity across methylation events of the same type. To enable nanopore sequencing for broadly applicable methylation discovery, we generated a training dataset from an assortment of bacterial species and developed a method, named nanodisco (https://github.com/fanglab/nanodisco), that couples the identification and fine mapping of the three forms of methylation into a multi-label classification framework. We applied it to individual bacteria and the mouse gut microbiome for reliable methylation discovery. In addition, we demonstrated the use of DNA methylation for binning metagenomic contigs, associating mobile genetic elements with their host genomes and identifying misassembled metagenomic contigs.

Original languageEnglish
Pages (from-to)491-498
Number of pages8
JournalNature Methods
Volume18
Issue number5
DOIs
StatePublished - May 2021

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