Scientific Publications
Use of alignment-free phylogenetics for rapid genome sequence-based typing of Helicobacter pylori virulence markers and antibiotic susceptibility
Journal of Clinical Microbiology, 53, 28772888
The development of genome sequencing technologies has made large collections of genome sequences available for pathogenic bacteria such as Helicobacter pylori, which colonises the gastric environment of approximately half the worlds' population and can cause pathologies and malignancies. The H. pylori genome displays very high levels of diversity generated through mutation, recombination and horizontal gene transfer, which complicates comparative genomics and molecular epidemiology. In this study we demonstrate that Feature Frequency Profiling (FFP), an alignment-free sequence comparison tool, can be used for rapid phylogenetic analysis of genomes and annotated proteomes of H. pylori. FFP-derived phylogenetic trees of seven gastric Helicobacter species matched those obtained by analysis of 16S rDNA and ribosomal proteins, and comparison of FFP analysis of 63 H. pylori genomes with core genome single nucleotide polymorphism (SNP)-based methods showed again comparable phylogenetic clustering, consistent with the genomotypes identified using multi-locus sequence typing (MLST). Finally, analysis of the distribution of virulence markers in 379 H. pylori whole genomes and proteomes showed a good conservation of genomotypes and linkage with phylogeographic characteristics, but no association with virulence markers, except for those previously described to be linked such as the cag pathogenicity island and vacA s1. In conclusion, feature frequency profiling can be used to rapidly analyse large collections of H. pylori genome sequences, which are too divergent for SNP-based analyses. When coupled with virulence marker genotyping, FFP-based phylogenetic clustering is a powerful tool for analysis linkages between genomotypes, phylogeographic information and pathogenicity potential, as shown with H. pylori as example.
Journal of Clinical Microbiology, 53, 28772888
View Publication
