The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers

Jason Sahl, Adam Vazquez, Carina Hall, Joseph Busch, Apichai Tuanyok, Mark Mayo, James Schupp, Madeline Lummis, Talima Pearson, Kenzie Shippy, Rebecca Colman, Christopher Allender, Vanessa Rigas, Derek Sarovich, Erin Price, Alex Hutcheson, Jonas Korlach, John LiPuma, Jason Ladner, Sean LovettGalina Koroleva, Gustavo Palacios, Direk Limmanthurotsakul, Vanaporn Wuthiekanun, Gumphol Wongsuwan, Bart Currie, Paul Keim, David M Wagner

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    Abstract

    ABSTRACT Whole-genome sequence (WGS) data are commonly used to design diagnostic targets for the identification of bacterial pathogens. To do this effectively, genomics databases must be comprehensive to identify the strict core genome that is specific to the target pathogen. As additional genomes are analyzed, the core genome size is reduced and there is erosion of the target-specific regions due to commonality with related species, potentially resulting in the identification of false positives and/or false negatives.

    IMPORTANCE A comparative analysis of 1,130 Burkholderia genomes identified unique markers for many named species, including the human pathogens B. pseudomallei and B. mallei. Due to core genome reduction and signature erosion, only 38 targets specific to B. pseudomallei/mallei were identified. By using only public genomes, a larger number of markers were identified, due to undersampling, and this larger number represents the potential for false positives. This analysis has implications for the design of diagnostics for other species where the genomic space of the target and/or closely related species is not well defined.
    Original languageEnglish
    Pages (from-to)1-9
    Number of pages9
    JournalmBio
    Volume7
    Issue number5
    DOIs
    Publication statusPublished - 2016

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