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 Lovett; Galina Koroleva; Gustavo Palacios; Direk Limmanthurotsakul; Vanaporn Wuthiekanun; Gumphol Wongsuwan; Bart Currie; Paul Keim; David M Wagner

doi:10.1128/mBio.00846-16

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 language	English
Pages (from-to)	1-9
Number of pages	9
Journal	mBio
Volume	7
Issue number	5
DOIs	https://doi.org/10.1128/mBio.00846-16
Publication status	Published - 2016

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Sahl_2016_The_Effects_of_Signal_ErosionFinal published version, 1.43 MBLicence: CC BY

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Sahl, J., Vazquez, A., Hall, C., Busch, J., Tuanyok, A., Mayo, M., Schupp, J., Lummis, M., Pearson, T., Shippy, K., Colman, R., Allender, C., Rigas, V., Sarovich, D., Price, E., Hutcheson, A., Korlach, J., LiPuma, J., Ladner, J., ... Wagner, D. M. (2016). The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers. mBio, 7(5), 1-9. https://doi.org/10.1128/mBio.00846-16

Sahl, Jason ; Vazquez, Adam ; Hall, Carina ; Busch, Joseph ; Tuanyok, Apichai ; Mayo, Mark ; Schupp, James ; Lummis, Madeline ; Pearson, Talima ; Shippy, Kenzie ; Colman, Rebecca ; Allender, Christopher ; Rigas, Vanessa ; Sarovich, Derek ; Price, Erin ; Hutcheson, Alex ; Korlach, Jonas ; LiPuma, John ; Ladner, Jason ; Lovett, Sean ; Koroleva, Galina ; Palacios, Gustavo ; Limmanthurotsakul, Direk ; Wuthiekanun, Vanaporn ; Wongsuwan, Gumphol ; Currie, Bart ; Keim, Paul ; Wagner, David M. / The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers. In: mBio. 2016 ; Vol. 7, No. 5. pp. 1-9.

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title = "The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers",

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.",

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

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language = "English",

volume = "7",

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Sahl, J, Vazquez, A, Hall, C, Busch, J, Tuanyok, A, Mayo, M, Schupp, J, Lummis, M, Pearson, T, Shippy, K, Colman, R, Allender, C, Rigas, V, Sarovich, D, Price, E, Hutcheson, A, Korlach, J, LiPuma, J, Ladner, J, Lovett, S, Koroleva, G, Palacios, G, Limmanthurotsakul, D, Wuthiekanun, V, Wongsuwan, G, Currie, B, Keim, P & Wagner, DM 2016, 'The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers', mBio, vol. 7, no. 5, pp. 1-9. https://doi.org/10.1128/mBio.00846-16

The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers. / Sahl, Jason; Vazquez, Adam; Hall, Carina; Busch, Joseph; Tuanyok, Apichai; Mayo, Mark; Schupp, James; Lummis, Madeline; Pearson, Talima; Shippy, Kenzie; Colman, Rebecca; Allender, Christopher; Rigas, Vanessa; Sarovich, Derek; Price, Erin; Hutcheson, Alex; Korlach, Jonas; LiPuma, John; Ladner, Jason; Lovett, Sean; Koroleva, Galina; Palacios, Gustavo; Limmanthurotsakul, Direk; Wuthiekanun, Vanaporn; Wongsuwan, Gumphol; Currie, Bart; Keim, Paul; Wagner, David M.

In: mBio, Vol. 7, No. 5, 2016, p. 1-9.

Research output: Contribution to journal › Article › peer-review

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T1 - The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers

AU - Sahl, Jason

AU - Vazquez, Adam

AU - Hall, Carina

AU - Busch, Joseph

AU - Tuanyok, Apichai

AU - Mayo, Mark

AU - Schupp, James

AU - Lummis, Madeline

AU - Pearson, Talima

AU - Shippy, Kenzie

AU - Colman, Rebecca

AU - Allender, Christopher

AU - Rigas, Vanessa

AU - Sarovich, Derek

AU - Price, Erin

AU - Hutcheson, Alex

AU - Korlach, Jonas

AU - LiPuma, John

AU - Ladner, Jason

AU - Lovett, Sean

AU - Koroleva, Galina

AU - Palacios, Gustavo

AU - Limmanthurotsakul, Direk

AU - Wuthiekanun, Vanaporn

AU - Wongsuwan, Gumphol

AU - Currie, Bart

AU - Keim, Paul

AU - Wagner, David M

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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DO - 10.1128/mBio.00846-16

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EP - 9

JO - mBio

JF - mBio

SN - 2150-7511

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

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