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Profiling lateral gene transfer events in the human microbiome using WAAFLE
Tiffany Y Hsu1, Etienne Nzabarushimana1,2, Dennis Wong3
1Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Nature Microbiology
|January 3, 2025
Summary
Lateral gene transfer (LGT) is crucial for microbial evolution. A new tool, WAAFLE, reveals widespread LGT in human microbiomes, uncovering over 100,000 new events and highlighting its significant role in genomic diversification.
Area of Science:
- Microbiology
- Genomics
- Bioinformatics
Background:
- Lateral gene transfer (LGT) drives microbial genomic diversification.
- Previous studies focused on isolate genomes, leaving the LGT landscape in complex human microbiomes poorly understood.
- Lack of standardized methods hinders LGT characterization from metagenomic data.
Purpose of the Study:
- To develop and validate a computational algorithm for profiling LGT from assembled metagenomes.
- To characterize the prevalence and patterns of LGT in diverse human microbiomes.
- To identify factors influencing LGT frequency and distribution.
Main Methods:
- Development and benchmarking of the WAAFLE (Workflow to Annotate Assemblies and Find LGT Events) algorithm.
- Application of WAAFLE to over 2,000 human metagenomes from various body sites.
- Analysis of LGT events, associated mobile elements, and functional enrichment.
Main Results:
- Identified over 100,000 high-confidence, previously uncharacterized LGT events.
- Discovered LGT events enriched for mobile elements and restriction-modification systems.
- Found LGT frequency influenced by biogeography, phylogenetic relatedness, and donor abundance.
Conclusions:
- The WAAFLE algorithm provides a sensitive and specific method for detecting intergenus LGT in metagenomes.
- Human microbiome LGT is more ubiquitous than previously recognized.
- Biogeographical factors and microbial community structure shape LGT networks.
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