GrafGen

GrafGen classifies Helicobacter pylori genomes and prophage populations according to genetic distance from reference populations to enable correction for bacterial population stratification in genome-wide association studies.

Key Features:

• Population Classification: Classifies H. pylori genomes into nine distinct bacterial populations (hpgpAfrica, hpgpAfrica-distant, hpgpAfroamerica, hpgpEuroamerica, hpgpMediterranea, hpgpEurope, hpgpEurasia, hpgpAsia, and hpgpAklavik86-like) based on genetic distance from reference populations with Africa, Europe, and Asia as vertex populations.
• Prophage Classification: Identifies four prophage groups by genetic distance clustering.
• Robustness to Down-sampling: Achieves greater than 97% concordance with classifications using 14,300 SNPs and greater than 90% concordance with 1,430 SNPs compared to the full set of approximately 143,000 biallelic SNPs with minor allele frequency greater than 1%.
• Visualization Tools: Integrates tools for geometric interpretation of ancestry structure.
• Extensible Framework: Adapted from GrafPop for haploid species with adequate reference data.

Scientific Applications:

• Population Stratification Correction: Corrects for bacterial population stratification as a major confounder in H. pylori genome-wide association studies.
• Ancestry Inference: Enables reliable inference of H. pylori ancestry to reflect human migration patterns through bacterial genomic variation.
• Genotype-Phenotype Association: Improves accuracy of genotype-phenotype association studies by accounting for population structure.
• Bacterial Genetics and Host-Pathogen Interaction Studies: Enhances studies of bacterial genetics and host-pathogen interactions through accurate population classification.

Methodology:

GrafGen uses distance-based inference adapted from the human ancestry tool GrafPop, with reference data from the H. pylori Genome Project (1,011 genomes from 50 countries) and validation using 255 GenBank sequences.