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MBio. 2016 Sep 20;7(5). pii: e00846-16. doi: 10.1128/mBio.00846-16.

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

Author information

1
Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA Translational Genomics Research Institute, Flagstaff, Arizona, USA.
2
Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
3
Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
4
Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
5
Translational Genomics Research Institute, Flagstaff, Arizona, USA.
6
Pacific Biosciences, University of Michigan, Ann Arbor, Michigan, USA.
7
Division of Pediatric Infectious Diseases, University of Michigan, Ann Arbor, Michigan, USA.
8
Center for Genome Sciences, USAMRIID, Fort Detrick, Maryland, USA.
9
Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
10
Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
11
Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA dave.wagner@nau.edu.

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.

PMID:
27651357
PMCID:
PMC5030356
DOI:
10.1128/mBio.00846-16
[Indexed for MEDLINE]
Free PMC Article

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