4.8 Article

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

Journal

NATURE METHODS
Volume 18, Issue 5, Pages 491-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41592-021-01109-3

Keywords

-

Funding

  1. Icahn Institute for Genomics and Multiscale Biology
  2. National Institutes of Health [R01 GM128955, R35 GM139655, R56 HG011095]

Ask authors/readers for more resources

In this study, a tool named nanodisco was developed to successfully apply nanopore sequencing for broadly applicable DNA methylation discovery and reliable methylation detection in bacteria and mouse gut microbiome. Furthermore, the application of DNA methylation for binning metagenomic contigs, associating mobile genetic elements with their host genomes, and identifying misassembled metagenomic contigs was demonstrated.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available