Genome-based model for differentiating between infection and carriage .

UNLABELLED

() is a clinically significant opportunistic pathogen, which can colonize multiple body sites in healthy individuals and cause various life-threatening diseases in both children and adults worldwide. The genetic backgrounds of that cause infection versus asymptomatic carriage vary widely, but the potential genetic elements (k-mers) associated with infection remain unknown, which leads to difficulties in differentiating infection isolates from harmless colonizers. Here, we address the disease-associated k-mers by using a comprehensive genome-wide association study (GWAS) to compare the genetic variation of isolates from clinical infection sites (272 isolates) with nasal carriage (240 isolates). This study uncovers consensus evidence that certain k-mers are overrepresented in infection isolates compared with carriage isolates, indicating the presence of specific genetic elements associated with infection. Moreover, the random forest (RF) model achieved a classification accuracy of 77% for predicting disease status (infection vs carriage), with 68% accuracy for a single highest-ranked k-mer, providing a simple target for identifying high-risk genotypes. Our findings suggest that the disease-causing is a pathogenic subpopulation harboring unique genomic variation that promotes invasion and infection, providing novel targets for clinical interventions.

IMPORTANCE

Defining the disease-causing isolates is the first step toward disease control. However, the disease-associated genetic elements of remain unknown, which leads to difficulties in differentiating infection isolates from harmless carriage isolates. Our comprehensive genome-wide association study (GWAS) found consensus evidence that certain genetic elements are overrepresented among infection isolates than carriage isolates, suggesting that the enrichment of disease-associated elements may promote infection. Notably, a single k-mer predictor achieved a high classification accuracy, which forms the basis for early diagnostics and interventions.