A genome-based model to predict the virulence of pseudomonas aeruginosa isolates

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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. aerugi-nosa isolates based on 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 phe-notypes 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 virulence predictions are derived 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 con-cept for the use of bacterial genomes to predict pathogenicity in P. aeruginosa and highlight the potential of this approach for predicting patient outcomes. IMPORTANCE Pseudomonas aeruginosa is a clinically important Gram-negative opportunistic pathogen. P. aeruginosa shows a large degree of genomic heterogeneity both through variation in sequences found throughout the species (core genome) and through the presence or absence of sequences in different isolates (accessory genome). P. aeruginosa isolates also differ markedly in their ability to cause disease. In this study, we used machine learning to predict the virulence level of P. aerugi-nosa isolates in a mouse bacteremia model based on genomic content. We show that both the accessory and core genomes are predictive of virulence. This study provides a machine learning framework to investigate relationships between bacterial genomes and complex phenotypes such as virulence.

Original languageEnglish (US)
Article numbere01527-20
Pages (from-to)1-19
Number of pages19
JournalmBio
Volume11
Issue number4
DOIs
StatePublished - Jul 1 2020

Keywords

  • Genome analysis
  • Machine learning
  • Modeling
  • Prediction
  • Pseudomonas aeruginosa
  • Virulence

ASJC Scopus subject areas

  • Microbiology
  • Virology

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