Phenotype-Based Threat Assessment.

Journal: Proceedings of the National Academy of Sciences of the United States of America
PMID:

Abstract

Bacterial pathogen identification, which is critical for human health, has historically relied on culturing organisms from clinical specimens. More recently, the application of machine learning (ML) to whole-genome sequences (WGSs) has facilitated pathogen identification. However, relying solely on genetic information to identify emerging or new pathogens is fundamentally constrained, especially if novel virulence factors exist. In addition, even WGSs with ML pipelines are unable to discern phenotypes associated with cryptic genetic loci linked to virulence. Here, we set out to determine if ML using phenotypic hallmarks of pathogenesis could assess potential pathogenic threat without using any sequence-based analysis. This approach successfully classified potential pathogenetic threat associated with previously machine-observed and unobserved bacteria with 99% and 85% accuracy, respectively. This work establishes a phenotype-based pipeline for potential pathogenic threat assessment, which we term PathEngine, and offers strategies for the identification of bacterial pathogens.

Authors

  • Jing Yang
    Beijing Novartis Pharma Co. Ltd., Beijing, China.
  • Mohammed Eslami
    Data Science, Netrias, LLC, Annapolis, MD 21409, USA.
  • Yi-Pei Chen
    Netrias, LLC, Cambridge, MA 02142.
  • Mayukh Das
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Dongmei Zhang
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Shaorong Chen
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Alexandria-Jade Roberts
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Mark Weston
    Data Science, Netrias, LLC, Annapolis, MD 21409, USA.
  • Angelina Volkova
    Netrias, LLC, Cambridge, MA 02142.
  • Kasra Faghihi
    Netrias, LLC, Cambridge, MA 02142.
  • Robbie K Moore
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Robert C Alaniz
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Alice R Wattam
    Biocomplexity Institute and Initiative, University of Virginia, Charlottesville, VA 22904.
  • Allan Dickerman
    Biocomplexity Institute and Initiative, University of Virginia, Charlottesville, VA 22904.
  • Clark Cucinell
    Biocomplexity Institute and Initiative, University of Virginia, Charlottesville, VA 22904.
  • Jarred Kendziorski
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Sean Coburn
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Holly Paterson
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Osahon Obanor
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Jason Maples
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Stephanie Servetas
    Complex Microbial Systems Group, Biomaterials and Biosystems Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899.
  • Jennifer Dootz
    Complex Microbial Systems Group, Biomaterials and Biosystems Division, Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20899.
  • Qing-Ming Qin
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • James E Samuel
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Arum Han
    Department of Electrical and Computer Engineering, Texas A&M University, College Station, TX 77843.
  • Erin J van Schaik
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.
  • Paul de Figueiredo
    Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX 77807.