Metagenomic strain-resolved DNA modification patterns link extrachromosomal genetic elements to host strains

Area of Science:

• Microbial epigenomics
• Metagenomics
• Bioinformatics

Background:

• DNA modification is crucial for microbial defense against extrachromosomal genetic elements (ECEs).
• ECEs typically mimic their host's DNA modification patterns.
• Existing tools for DNA modification detection are ineffective for metagenomic analysis.

Purpose of the Study:

• To introduce MODIFI, a novel software for detecting DNA modifications within metagenomes.
• To enable the linkage of ECEs to their microbial hosts using metagenomic data.
• To overcome the limitations of current tools in analyzing microbial epigenomics at scale.

Main Methods:

• MODIFI utilizes PacBio HiFi reads to calculate background signal levels for k-mers, assuming most are unmodified.
• This approach eliminates the necessity for matched control experiments.
• The software was validated using over 1,000 isolate and mock microbiome datasets.

Main Results:

• MODIFI successfully identified 315 strain-resolved, non-redundant ECE-host linkages in diverse metagenomes.
• The study demonstrated simultaneous alterations in host and plasmid methylation motifs in Enterococcus faecalis within infant gut microbiomes.
• The software proves effective in linking ECEs to their hosts in complex microbial communities.

Conclusions:

• MODIFI addresses a significant challenge in DNA modification analysis, particularly in metagenomic contexts.
• This tool provides a foundational capability for advancing the field of microbial epigenomics.
• MODIFI facilitates a deeper understanding of host-ECE interactions and microbial community dynamics.