WAAFLE

WAAFLE profiles lateral gene transfer events in assembled metagenomes.

Key Features:

• High specificity for intergenus LGT: WAAFLE prioritizes specificity while maintaining high sensitivity for detecting intergenus lateral gene transfer events.
• Assembly-based analysis: WAAFLE operates on assembled metagenomes rather than raw reads.
• High-confidence LGT identification: The method identifies high-confidence previously uncharacterized LGT events, with validation showing ~2 LGT events per microbial genome-equivalent.
• Network analysis of donor-recipient relationships: WAAFLE enables characterization of LGT networks in which hub taxa donate unequally with phylogenetic neighbours.

Scientific Applications:

• Human microbiome LGT profiling: WAAFLE has been applied to >2,000 human metagenomes from diverse body sites to characterize the landscape of lateral gene transfer in personal microbiomes.
• Characterization of LGT functional enrichment: WAAFLE identifies LGT events enriched for mobile elements and restriction-modification functions associated with the destruction of foreign DNA.
• Analysis of LGT biogeographic and phylogenetic patterns: WAAFLE enables investigation of how LGT frequency is influenced by biogeography, phylogenetic similarity of involved pairs (for example, Fusobacterium periodonticum and F. nucleatum), and donor abundance.

Methodology:

WAAFLE is a computational algorithm that annotates assemblies and finds LGT events. The method was developed, benchmarked and validated for profiling LGT from assembled metagenomes.