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A Genome-based Model to Predict the Virulence of Pseudomonas aeruginosa Isolates

By Nathan B. Pincus, Egon A. Ozer, Jonathan P. Allen, Marcus Nguyen, James J Davis, Deborah R. Winter, Chih-Hsien Chuang, Cheng-Hsun Chiu, Laura Zamorano, Antonio Oliver, Alan R. Hauser

Posted 12 Jun 2020
bioRxiv DOI: 10.1101/2020.06.09.143610

Variation in the genome of Pseudomonas aeruginosa, an important pathogen, can have dramatic impacts on the bacterium's ability to cause disease. We therefore asked whether it was possible to predict the virulence of P. aeruginosa isolates based upon their genomic content. We applied a machine learning approach to a genetically and phenotypically diverse collection of 115 clinical P. aeruginosa isolates using genomic information and corresponding virulence phenotypes in a mouse model of bacteremia. We defined the accessory genome of these isolates through the presence or absence of accessory genomic elements (AGEs), sequences present in some strains but not others. Machine learning models trained using AGEs were predictive of virulence, with a mean nested cross-validation accuracy of 75% using the random forest algorithm. However, individual AGEs did not have a large influence on the algorithm’s performance, suggesting instead that the virulence prediction derives from a diffuse genomic signature. These results were validated with an independent test set of 25 P. aeruginosa isolates whose virulence was predicted with 72% accuracy. Machine learning models trained using core genome single nucleotide variants and whole genome k-mers also predicted virulence. Our findings are a proof of concept for the use of bacterial genomes to predict pathogenicity in P. aeruginosa and highlight the potential of this approach for predicting patient outcomes.

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