CRHP Finder

CRHP Finder identifies clarithromycin resistance in Helicobacter pylori by detecting specific mutations in domain V of the 23S rRNA gene from whole-genome sequencing data.

Key Features:

• Mutation Detection: Targets nucleotide positions 2142, 2143, 2182, 2244, and 2712 corresponding to A2142G, A2143G, A2142C, T2182C, C2244T, and T2712C in the 23S rRNA gene.
• Alignment Methodology: Employs k-mer alignment (KMA) to align raw sequencing reads in fastq format to the reference 23S rRNA gene sequence using E. coli numbering and determine nucleotide distributions at specified positions.
• Genotypic Prediction: Compares detected nucleotide distributions against known resistance-conferring mutations to generate a genotypic prediction of clarithromycin resistance phenotype.
• Validation and Accuracy: Validated on 137 paired-end sequencing datasets from a well-characterized H. pylori strain collection and correctly identified reported resistance mutations.
• Clinical Study Findings: In 23 Danish H. pylori strains collected January 2017–September 2019, detected A2143G in all resistant strains and observed T2182C and C2244T exclusively in susceptible strains.

Scientific Applications:

• Resistance Monitoring: Tracking the prevalence of specific 23S rRNA mutations associated with clarithromycin resistance.
• Treatment Optimization: Informing antibiotic therapy decisions by identifying genotypic clarithromycin resistance.
• Epidemiological Studies: Facilitating studies of the distribution and evolution of resistance-conferring mutations across populations.

Methodology:

Alignment of raw fastq reads to the H. pylori 23S rRNA reference using k-mer alignment (KMA), extraction of nucleotide distributions at positions 2142, 2143, 2182, 2244, and 2712 (E. coli numbering), and comparison of observed nucleotides to A2142G, A2143G, A2142C, T2182C, C2244T, and T2712C to produce genotypic resistance predictions.