July 7, 2019  |  

The effects of signal erosion and core genome reduction on the identification of diagnostic markers.

Authors: Sahl, Jason W and Vazquez, Adam J and Hall, Carina M and Busch, Joseph D and Tuanyok, Apichai and Mayo, Mark and Schupp, James M and Lummis, Madeline and Pearson, Talima and Shippy, Kenzie and Colman, Rebecca E and Allender, Christopher J and Theobald, Vanessa and Sarovich, Derek S and Price, Erin P and Hutcheson, Alex and Korlach, Jonas and LiPuma, John J and Ladner, Jason and Lovett, Sean and Koroleva, Galina and Palacios, Gustavo and Limmathurotsakul, Direk and Wuthiekanun, Vanaporn and Wongsuwan, Gumphol and Currie, Bart J and Keim, Paul and Wagner, David M

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.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. Copyright © 2016 Sahl et al.

Journal: mBio
DOI: 10.1128/mBio.00846-16
Year: 2016

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