Flanker

Flanker performs alignment-free extraction and clustering of gene flanking sequences to characterize mobile genetic elements (MGEs) and investigate horizontal gene transfer of antimicrobial resistance genes.

Key Features:

• Implementation: Provided as a Python package for programmatic analysis of genomic sequence files.
• Alignment-free clustering: Clusters flanking sequences into "flank patterns" using Mash distances to compare sequence similarity without requiring prior structural annotation of MGEs.
• Flexible parameterization: Supports separate analysis of upstream and downstream regions with variable flanking-sequence lengths.
• Plasmid-associated analysis: Applied to datasets describing plasmid-associated carriage of carbapenemase genes, including blaOXA-48 and blaKPC-2/3, to identify distinct flank clusters.
• Identification of novel profiles: Detects novel Tn4401 profiles not characterized by tools such as TETyper or MobileElementFinder.
• Epidemiological associations: Associates flank patterns with geographical regions and antibiotic susceptibility phenotypes as potential epidemiological markers.

Scientific Applications:

• Mobile genetic element characterization: Characterizes structural variation in gene flanks to study MGE diversity.
• Horizontal gene transfer studies: Traces the dissemination of antimicrobial resistance genes via flanking-sequence similarity.
• Antimicrobial resistance surveillance: Analyzes flanking regions of resistance genes such as blaOXA-48 and blaKPC-2/3 to inform molecular epidemiology.
• Epidemiological marker discovery: Identifies flank-pattern associations with geography and antibiotic susceptibility phenotypes for use in epidemiological investigations.

Methodology:

Flanker annotates FASTA/multi-FASTA files for specified genes, writes upstream and downstream flanking sequences to new FASTA files, and optionally clusters those sequences using alignment-free Mash distances to group "flank patterns" by sequence identity.