Systems biology approach to functionally assess the Clostridioides difficile pangenome reveals genetic diversity with discriminatory power

Author:

Norsigian Charles J.1,Danhof Heather A.23ORCID,Brand Colleen K.23,Midani Firas S.23ORCID,Broddrick Jared T.4,Savidge Tor C.5,Britton Robert A.23,Palsson Bernhard O.1ORCID,Spinler Jennifer K.4,Monk Jonathan M.1ORCID

Affiliation:

1. Department of Bioengineering, University of California San Diego, La Jolla, CA 92039

2. Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX 77030

3. Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX 77030

4. Space Biosciences Research Branch, Space Biosciences Division, NASA Ames Research Center, Moffett Field, CA 94035

5. Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030

Abstract

Significance Clostridioides difficile infections are the most common source of hospital-acquired infections and are responsible for an extensive burden on the health care system. Strains of the C. difficile species comprise diverse lineages and demonstrate genome variability, with advantageous trait acquisition driving the emergence of endemic lineages. Here, we present a systems biology analysis of C. difficile that evaluates strain-specific genotypes and phenotypes to investigate the overall diversity of the species. We develop a strain typing method based on similarity of accessory genomes to identify and contextualize genetic loci capable of discriminating between strain groups.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Reference105 articles.

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