Background

Sequencing of the 16S rRNA gene is a commonly used and culture-free way to identify many of the taxa present in a metagenomic sample, but the phylogenetic resolution is limited and the entire genomic architecture outside of this single gene is ignored. Alternatively, whole metagenome shotgun sequencing collects data from the entire genome, theoretically making it possible to reconstruct the constituent genomes in the community. In practice, however, the complexity of the sequencing data makes analysis difficult, especially when the output sequences only contain 100-300 bases per read.

One of the primary challenges in making sense of metagenomic sequencing data is sorting the mixture of reads deriving from many organisms into organism-specific groups, or ‘bins’. The precise methylation patterns in the DNA often differ between bacterial species or even strains. These differences can be leveraged to help organize metagenomic sequences into organism-specific groups. The combination of methylation and sequencing information provides unprecedented power to interrogate complex microbial samples.

Technology Overview

Despite the growing appreciation for the profound ways in which the microbiome can impact human health, comprehensive characterization of microbial populations remains challenging and labor intensive. This is a novel method that provides unprecedented resolution of the species and strains present in complex microbial communities that takes advantage of DNA methylation that creates organism-specific, epigenetic signatures in bacterial genomes ().

Stage of Development

Currently expanding applications of technology to multiple sequencing platforms

Benefits

Unique ability to group species- and strains- specific DNA using cell-wide patterns of methylation.
Independent of sequence composition and coverage metrics.
Enables the association of plasmids and other mobile genetic elements to their host chromosomes.

Applications

Profiling human microbiomes to diagnose disease or monitor effects of medication
Monitoring spread of mobile genetic elements conferring antibiotic resistance and other clinically relevant phenotypes
Human “Enterotyping” - personalized medicine to identify effective antibiotic therapies
Identification of “protective” microbiome profiles

A Novel Method for High-Resolution Analysis of Microbiome Using Microbial DNA Methylation Information

IP Status