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Antibiotic-Specific Genotype-Phenotype Concordance and Cross-Database Interoperability in Public Escherichia coli/Shigella WGS-AMR Metadata.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Antibiotic-Specific Genotype-Phenotype Concordance and Cross-Database Interoperability in Public Escherichia coli/Shigella WGS-AMR Metadata.
Συγγραφείς: Alshehri AA; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia.; Department of Infection Prevention and Control, Najran University Hospital, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia.; Genomics and Genetics Unit, Health Research Center, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia.
Πηγή: International journal of molecular sciences [Int J Mol Sci] 2026 Aug 10; Vol. 27 (16). Date of Electronic Publication: 2026 Aug 10.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
Imprint Name(s): Original Publication: Basel, Switzerland : MDPI, [2000-
Ιατρικοί όροι (MeSH): Anti-Bacterial Agents*/pharmacology , Escherichia coli*/genetics , Escherichia coli*/drug effects , Drug Resistance, Bacterial*/genetics , Metadata*, Phenotype ; Microbial Sensitivity Tests ; Genotype ; Databases, Genetic ; Whole Genome Sequencing ; Genome, Bacterial
Περίληψη: Public pathogen-genomics repositories are increasingly used for antimicrobial resistance (AMR) surveillance, yet the reliability and interoperability of database-derived genotype-phenotype inference remain incompletely characterized. This study evaluated antibiotic-specific concordance between exported AMR genotype annotations and antimicrobial susceptibility testing (AST) phenotypes in the NCBI Pathogen Detection metadata for the Escherichia coli/Shigella organism group and used BV-BRC to assess complementary phenotype-related coverage and cross-resource linkage. Frozen NCBI Pathogen Detection and BV-BRC exports were analyzed retrospectively. NCBI records were filtered for assembly accessions, AMR genotype annotations, and interpretable resistant or susceptible AST results. Prespecified antibiotic-specific mapping rules were applied. Performance metrics, including sensitivity, specificity, accuracy, balanced accuracy, positive and negative predictive values and F1-score, were calculated, and their 95% confidence intervals were estimated using 10,000 isolate-level bootstrap replicates. BV-BRC was evaluated descriptively for phenotype-related coverage, evidence type, and accession overlap. Among 539,918 NCBI records, 10,201 met prespecified criteria for assembly accession, AMR genotype annotation, and interpretable resistant/susceptible AST data. These records generated 56,141 genotype-phenotype comparisons across eight priority antibiotics. Concordance was high for tetracycline (accuracy, 98.4%; F1-score, 98.1%) and ceftriaxone (accuracy, 97.9%; F1-score, 94.6%), but lower for amoxicillin-clavulanic acid (accuracy, 73.6%; F1-score, 44.5%), indicating antibiotic-specific limits of genotype-field inference. Discordance was explicitly separated into 2524 genotype-positive/phenotype-susceptible and 923 phenotype-resistant observations with no mapped genomic evidence of resistance. BV-BRC contributed 21,298 taxonomy-strict E. coli/Shigella genomes and 4745 phenotype-linked identifiers. Although 15,214 BioSample and 10,121 assembly accessions were shared across exports, no analysis-ready overlap remained between the final NCBI genotype-AST and BV-BRC phenotype-linked subsets after eligibility filtering. Public WGS-AMR databases can support large-scale surveillance-oriented concordance analyses, but performance is antibiotic specific and depends on mapping rules, phenotype definitions, evidence provenance, and accession linkage. These estimates do not constitute clinical diagnostic validation and should not replace phenotypic AST. Because the analysis was conducted at the combined organism-group level, these estimates may mask species-, pathotype-, or lineage-specific resistance dynamics.
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Microb Genom. 2022 Jan;8(1):. (PMID: 35072601)
Antimicrob Agents Chemother. 2025 May 7;69(5):e0108224. (PMID: 40227048)
Lancet. 2022 Feb 12;399(10325):629-655. (PMID: 35065702)
Nat Rev Genet. 2012 Sep;13(9):601-612. (PMID: 22868263)
Mol Biol Evol. 2023 Jan 4;40(1):. (PMID: 36585846)
Clin Infect Dis. 2021 Oct 20;73(8):1537-1539. (PMID: 34240118)
J Antimicrob Chemother. 2020 Dec 1;75(12):3491-3500. (PMID: 32780112)
PLoS One. 2011;6(10):e25825. (PMID: 22053181)
J Antimicrob Chemother. 2015 Oct;70(10):2763-9. (PMID: 26142410)
Front Microbiol. 2022 Jun 10;13:804627. (PMID: 35756053)
J Clin Microbiol. 2014 Apr;52(4):1182-91. (PMID: 24501024)
J Antimicrob Chemother. 2025 Nov 4;80(11):3123-3132. (PMID: 40985147)
Nat Commun. 2025 Sep 30;16(1):8669. (PMID: 41028731)
Genome Med. 2022 Feb 16;14(1):15. (PMID: 35172877)
One Health Outlook. 2020;2(1):20. (PMID: 33103064)
BMC Microbiol. 2023 Aug 18;23(1):225. (PMID: 37596530)
Nat Rev Genet. 2024 Feb;25(2):142-157. (PMID: 37749210)
J Appl Microbiol. 2024 Sep 2;135(9):. (PMID: 39113269)
Nucleic Acids Res. 2026 Jan 6;54(D1):D715-D723. (PMID: 41251138)
J Clin Microbiol. 2019 Feb 27;57(3):. (PMID: 30381421)
Front Microbiol. 2020 Apr 03;11:549. (PMID: 32318038)
Lancet. 2024 Sep 28;404(10459):1199-1226. (PMID: 39299261)
Clin Microbiol Infect. 2017 Jan;23(1):2-22. (PMID: 27890457)
PLOS Glob Public Health. 2025 Nov 24;5(11):e0005256. (PMID: 41284650)
Front Microbiol. 2026 Apr 28;17:1842717. (PMID: 42131209)
Appl Environ Microbiol. 2015 Oct 30;82(2):459-66. (PMID: 26519386)
J Antimicrob Chemother. 2005 May;55(5):768-72. (PMID: 15761065)
Sci Data. 2025 May 13;12(1):784. (PMID: 40360501)
Microb Genom. 2020 Feb;6(2):. (PMID: 32048983)
Nucleic Acids Res. 2023 Jan 6;51(D1):D678-D689. (PMID: 36350631)
Eur J Clin Microbiol Infect Dis. 2021 Nov;40(11):2371-2377. (PMID: 34175999)
J Glob Antimicrob Resist. 2019 Dec;19:136-143. (PMID: 31005733)
Antimicrob Agents Chemother. 2016 Aug 22;60(9):5515-20. (PMID: 27381390)
Nat Commun. 2020 Jun 1;11(1):2719. (PMID: 32483195)
Artif Intell Med. 2022 Aug;130:102326. (PMID: 35809965)
Lancet Microbe. 2023 Dec;4(12):e1047-e1055. (PMID: 37977162)
Virulence. 2026 Dec;17(1):2668179. (PMID: 42102272)
Sci Rep. 2021 Jun 16;11(1):12728. (PMID: 34135355)
Nat Rev Genet. 2019 Jun;20(6):356-370. (PMID: 30886350)
J Antimicrob Chemother. 2017 Dec 01;72(12):3288-3297. (PMID: 28961934)
Antibiotics (Basel). 2022 Oct 12;11(10):. (PMID: 36290058)
J Hazard Mater. 2026 Aug 1;514:142819. (PMID: 42378761)
NPJ Antimicrob Resist. 2024 Jun 17;2(1):16. (PMID: 39843577)
Nat Med. 2020 Jun;26(6):832-841. (PMID: 32528156)
J Clin Microbiol. 2017 Feb;55(2):616-623. (PMID: 27974538)
Antimicrob Agents Chemother. 2019 Oct 22;63(11):. (PMID: 31427293)
Microb Genom. 2023 Jan;9(1):. (PMID: 36748616)
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Sci Rep. 2023 Jan 9;13(1):449. (PMID: 36624272)
Clin Microbiol Infect. 2026 Jun;32(7S):S1-S34. (PMID: 42142806)
Nat Commun. 2023 Jan 4;14(1):60. (PMID: 36599823)
Grant Information: NU/GP/MRC/14/326-1 Najran University
Contributed Indexing: Keywords: BV-BRC; Escherichia coli/Shigella; NCBI Pathogen Detection; antimicrobial resistance; antimicrobial susceptibility testing; genomic surveillance; genotype–phenotype concordance; whole-genome sequencing
Substance Nomenclature: 0 (Anti-Bacterial Agents)
Entry Date(s): Date Created: 20260827 Date Completed: 20260827 Latest Revision: 20260829
Update Code: 20260829
PubMed Central ID: PMC13513162
DOI: 10.3390/ijms27167157
PMID: 42653162
Βάση Δεδομένων: MEDLINE
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  Data: Antibiotic-Specific Genotype-Phenotype Concordance and Cross-Database Interoperability in Public Escherichia coli/Shigella WGS-AMR Metadata.
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  Data: <searchLink fieldCode="AU" term="%22Alshehri+AA%22">Alshehri AA</searchLink>; Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia.; Department of Infection Prevention and Control, Najran University Hospital, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia.; Genomics and Genetics Unit, Health Research Center, Najran University, P.O. Box 1988, Najran 61441, Saudi Arabia.
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  Data: Public pathogen-genomics repositories are increasingly used for antimicrobial resistance (AMR) surveillance, yet the reliability and interoperability of database-derived genotype-phenotype inference remain incompletely characterized. This study evaluated antibiotic-specific concordance between exported AMR genotype annotations and antimicrobial susceptibility testing (AST) phenotypes in the NCBI Pathogen Detection metadata for the Escherichia coli/Shigella organism group and used BV-BRC to assess complementary phenotype-related coverage and cross-resource linkage. Frozen NCBI Pathogen Detection and BV-BRC exports were analyzed retrospectively. NCBI records were filtered for assembly accessions, AMR genotype annotations, and interpretable resistant or susceptible AST results. Prespecified antibiotic-specific mapping rules were applied. Performance metrics, including sensitivity, specificity, accuracy, balanced accuracy, positive and negative predictive values and F1-score, were calculated, and their 95% confidence intervals were estimated using 10,000 isolate-level bootstrap replicates. BV-BRC was evaluated descriptively for phenotype-related coverage, evidence type, and accession overlap. Among 539,918 NCBI records, 10,201 met prespecified criteria for assembly accession, AMR genotype annotation, and interpretable resistant/susceptible AST data. These records generated 56,141 genotype-phenotype comparisons across eight priority antibiotics. Concordance was high for tetracycline (accuracy, 98.4%; F1-score, 98.1%) and ceftriaxone (accuracy, 97.9%; F1-score, 94.6%), but lower for amoxicillin-clavulanic acid (accuracy, 73.6%; F1-score, 44.5%), indicating antibiotic-specific limits of genotype-field inference. Discordance was explicitly separated into 2524 genotype-positive/phenotype-susceptible and 923 phenotype-resistant observations with no mapped genomic evidence of resistance. BV-BRC contributed 21,298 taxonomy-strict E. coli/Shigella genomes and 4745 phenotype-linked identifiers. Although 15,214 BioSample and 10,121 assembly accessions were shared across exports, no analysis-ready overlap remained between the final NCBI genotype-AST and BV-BRC phenotype-linked subsets after eligibility filtering. Public WGS-AMR databases can support large-scale surveillance-oriented concordance analyses, but performance is antibiotic specific and depends on mapping rules, phenotype definitions, evidence provenance, and accession linkage. These estimates do not constitute clinical diagnostic validation and should not replace phenotypic AST. Because the analysis was conducted at the combined organism-group level, these estimates may mask species-, pathotype-, or lineage-specific resistance dynamics.
– Name: Ref
  Label: References
  Group: RefInfo
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(PMID: <searchLink fieldCode="PM" term="%2232780112%22">32780112)</searchLink><br />PLoS One. 2011;6(10):e25825. (PMID: <searchLink fieldCode="PM" term="%2222053181%22">22053181)</searchLink><br />J Antimicrob Chemother. 2015 Oct;70(10):2763-9. (PMID: <searchLink fieldCode="PM" term="%2226142410%22">26142410)</searchLink><br />Front Microbiol. 2022 Jun 10;13:804627. (PMID: <searchLink fieldCode="PM" term="%2235756053%22">35756053)</searchLink><br />J Clin Microbiol. 2014 Apr;52(4):1182-91. (PMID: <searchLink fieldCode="PM" term="%2224501024%22">24501024)</searchLink><br />J Antimicrob Chemother. 2025 Nov 4;80(11):3123-3132. (PMID: <searchLink fieldCode="PM" term="%2240985147%22">40985147)</searchLink><br />Nat Commun. 2025 Sep 30;16(1):8669. (PMID: <searchLink fieldCode="PM" term="%2241028731%22">41028731)</searchLink><br />Genome Med. 2022 Feb 16;14(1):15. (PMID: <searchLink fieldCode="PM" term="%2235172877%22">35172877)</searchLink><br />One Health Outlook. 2020;2(1):20. (PMID: <searchLink fieldCode="PM" term="%2233103064%22">33103064)</searchLink><br />BMC Microbiol. 2023 Aug 18;23(1):225. (PMID: <searchLink fieldCode="PM" term="%2237596530%22">37596530)</searchLink><br />Nat Rev Genet. 2024 Feb;25(2):142-157. (PMID: <searchLink fieldCode="PM" term="%2237749210%22">37749210)</searchLink><br />J Appl Microbiol. 2024 Sep 2;135(9):. (PMID: <searchLink fieldCode="PM" term="%2239113269%22">39113269)</searchLink><br />Nucleic Acids Res. 2026 Jan 6;54(D1):D715-D723. (PMID: <searchLink fieldCode="PM" term="%2241251138%22">41251138)</searchLink><br />J Clin Microbiol. 2019 Feb 27;57(3):. (PMID: <searchLink fieldCode="PM" term="%2230381421%22">30381421)</searchLink><br />Front Microbiol. 2020 Apr 03;11:549. (PMID: <searchLink fieldCode="PM" term="%2232318038%22">32318038)</searchLink><br />Lancet. 2024 Sep 28;404(10459):1199-1226. (PMID: <searchLink fieldCode="PM" term="%2239299261%22">39299261)</searchLink><br />Clin Microbiol Infect. 2017 Jan;23(1):2-22. 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(PMID: <searchLink fieldCode="PM" term="%2227974538%22">27974538)</searchLink><br />Antimicrob Agents Chemother. 2019 Oct 22;63(11):. (PMID: <searchLink fieldCode="PM" term="%2231427293%22">31427293)</searchLink><br />Microb Genom. 2023 Jan;9(1):. (PMID: <searchLink fieldCode="PM" term="%2236748616%22">36748616)</searchLink><br />J Antimicrob Chemother. 2017 Sep 1;72(9):2496-2502. (PMID: <searchLink fieldCode="PM" term="%2228591819%22">28591819)</searchLink><br />Sci Rep. 2023 Jan 9;13(1):449. (PMID: <searchLink fieldCode="PM" term="%2236624272%22">36624272)</searchLink><br />Clin Microbiol Infect. 2026 Jun;32(7S):S1-S34. (PMID: <searchLink fieldCode="PM" term="%2242142806%22">42142806)</searchLink><br />Nat Commun. 2023 Jan 4;14(1):60. (PMID: <searchLink fieldCode="PM" term="%2236599823%22">36599823)</searchLink>
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  Data: <i>Keywords: </i>BV-BRC; Escherichia coli/Shigella; NCBI Pathogen Detection; antimicrobial resistance; antimicrobial susceptibility testing; genomic surveillance; genotype–phenotype concordance; whole-genome sequencing
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      – SubjectFull: Phenotype
        Type: general
      – SubjectFull: Microbial Sensitivity Tests
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      – SubjectFull: Genotype
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      – SubjectFull: Escherichia coli drug effects
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      – TitleFull: Antibiotic-Specific Genotype-Phenotype Concordance and Cross-Database Interoperability in Public Escherichia coli/Shigella WGS-AMR Metadata.
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      – PersonEntity:
          Name:
            NameFull: Alshehri AA
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 10
              M: 08
              Text: 2026 Aug 10
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1422-0067
          Numbering:
            – Type: volume
              Value: 27
            – Type: issue
              Value: 16
          Titles:
            – TitleFull: International journal of molecular sciences
              Type: main
ResultId 1