Contrasting approaches to genome-wide association studies impact the detection of resistance mechanisms in Staphylococcus aureus

摘要: Abstract Rapid detection of antibiotic resistance using whole-genome sequencing (WGS) could improve clinical outcomes and limit the spread resistance. For this to succeed, we need an accurate way linking genotype phenotype, that identifies new mechanisms as they appear. To assess how close are goal, characterized antimicrobial determinants in >4,000 Staphylococcus aureus genomes isolates associated with bloodstream infection United Kingdom Ireland. We sought answer three questions: 1) well did known explain phenotypic our collection, 2) many previously identified appeared 3) these were detectable four contrasting genome-wide association study (GWAS) methods. Resistance prediction based on was 98.8% accurate. challenges correcting for population structure, clustering orthologous genes, identifying causal rare or common phenotypes, which reduced recovery mechanisms. Limited sensitivity specificity methods made GWAS-discovered hits alone less than literature-derived genetic determinants. However, GWAS novel mutations resistance, including five rpsJ, improved tetracycline 28 isolates, a T118I substitution fusA resulted better fusidic acid 5 isolates. Thus, approaches conjunction testing data can support development comprehensive databases enable real-time use WGS patient management.