title: The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers.
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.
  
  
  
  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.
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Sahl
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Vazquez
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Carina M
authors.initials: CM
authors.lastname: Hall
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Busch
authors.affiliation: Emerging Pathogens Institute, University of Florida, Gainesville, Florida, USA.
authors.forename: Apichai
authors.initials: A
authors.lastname: Tuanyok
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Mayo
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Schupp
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Madeline
authors.initials: M
authors.lastname: Lummis
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Talima
authors.initials: T
authors.lastname: Pearson
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Kenzie
authors.initials: K
authors.lastname: Shippy
authors.affiliation: Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: Rebecca E
authors.identifier: 0000-0002-6854-2100
authors.initials: RE
authors.lastname: Colman
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Allender
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Theobald
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Derek S
authors.identifier: 0000-0002-6944-3980
authors.initials: DS
authors.lastname: Sarovich
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Erin P
authors.identifier: 0000-0002-1079-4882
authors.initials: EP
authors.lastname: Price
authors.affiliation: Pacific Biosciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Hutcheson
authors.affiliation: Pacific Biosciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Jonas
authors.initials: J
authors.lastname: Korlach
authors.affiliation: Division of Pediatric Infectious Diseases, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: John J
authors.initials: JJ
authors.lastname: LiPuma
authors.affiliation: Center for Genome Sciences, USAMRIID, Fort Detrick, Maryland, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Ladner
authors.affiliation: Center for Genome Sciences, USAMRIID, Fort Detrick, Maryland, USA.
authors.forename: Sean
authors.initials: S
authors.lastname: Lovett
authors.affiliation: Center for Genome Sciences, USAMRIID, Fort Detrick, Maryland, USA.
authors.forename: Galina
authors.initials: G
authors.lastname: Koroleva
authors.affiliation: Center for Genome Sciences, USAMRIID, Fort Detrick, Maryland, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palacios
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Direk
authors.initials: D
authors.lastname: Limmathurotsakul
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
authors.forename: Vanaporn
authors.initials: V
authors.lastname: Wuthiekanun
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Mahidol University, Bangkok, Thailand.
authors.forename: Gumphol
authors.initials: G
authors.lastname: Wongsuwan
authors.affiliation: Global and Tropical Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia.
authors.forename: Bart J
authors.initials: BJ
authors.lastname: Currie
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA Translational Genomics Research Institute, Flagstaff, Arizona, USA.
authors.forename: Paul
authors.identifier: 0000-0003-0089-5820
authors.initials: P
authors.lastname: Keim
authors.affiliation: Center for Microbial Genetics and Genomics, Northern Arizona University, Flagstaff, Arizona, USA dave.wagner@nau.edu.
authors.forename: David M
authors.initials: DM
authors.lastname: Wagner
mesh_terms: D015373:Bacterial Typing Techniques; D019117:Burkholderia / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D030541:Databases, Genetic; D005189:False Positive Reactions; D005819:Genetic Markers; D016680:Genome, Bacterial; D006801:Humans; D057089:Pathology, Molecular / Q000379:methods; D017422:Sequence Analysis, DNA
chemical_list: D005819:Genetic Markers