Bringing TB genomics to the clinic: A comprehensive pipeline to predict antimicrobial susceptibility from genomic data, validated and accredited to ISO standards
Abstract Background Whole genome sequencing shows promise to improve the clinical management of tuberculosis, but bioinformatic tools tailored for clinical reporting and suitable for accreditation to ISO standards are currently lacking.Methods We developed tbtAMR, a comprehensive pipeline for analysis ofMycobacterium tuberculosisgenomic data, including inference of phenotypic susceptibility and lineage calling from both solid and broth (MGIT) cultures. We used local and publicly-availably real-world data (phenotype and genotype) and synthetic genomic data to determine the appropriate quality control metrics and extensively validate the pipeline for clinical use. We combined and curated the large global databases of resistance mutations, fine-tuned for clinical purposes, by minimising false-positives whilst maintaining accuracy.Findings tbtAMR accurately predicted lineages and phenotypic susceptibility for first- and second-line drugs, including from broth (MGIT) cultures. We designed and implemented a reporting template suitable for clinical and public health users and accredited the pipeline to ISO standards.Interpretation The tbtAMR pipeline is accurate and fit-for-purpose for clinical and public health uses. Report templates, validation methods and datasets are provided here to offer a pathway for laboratories to adopt and seek their own accreditation for this critical test, to improve the management of tuberculosis globally.Funding No specific funding was received for this study..
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Preprint| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
bioRxiv.org - (2023) vom: 10. Nov. Zur Gesamtaufnahme - year:2023 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Horan, Kristy [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.11.04.565651 |
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| PPN (Katalog-ID): |
XBI041451317 |
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| 520 | |a Abstract Background Whole genome sequencing shows promise to improve the clinical management of tuberculosis, but bioinformatic tools tailored for clinical reporting and suitable for accreditation to ISO standards are currently lacking.Methods We developed tbtAMR, a comprehensive pipeline for analysis ofMycobacterium tuberculosisgenomic data, including inference of phenotypic susceptibility and lineage calling from both solid and broth (MGIT) cultures. We used local and publicly-availably real-world data (phenotype and genotype) and synthetic genomic data to determine the appropriate quality control metrics and extensively validate the pipeline for clinical use. We combined and curated the large global databases of resistance mutations, fine-tuned for clinical purposes, by minimising false-positives whilst maintaining accuracy.Findings tbtAMR accurately predicted lineages and phenotypic susceptibility for first- and second-line drugs, including from broth (MGIT) cultures. We designed and implemented a reporting template suitable for clinical and public health users and accredited the pipeline to ISO standards.Interpretation The tbtAMR pipeline is accurate and fit-for-purpose for clinical and public health uses. Report templates, validation methods and datasets are provided here to offer a pathway for laboratories to adopt and seek their own accreditation for this critical test, to improve the management of tuberculosis globally.Funding No specific funding was received for this study. | ||
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| 700 | 1 | |a Webb, Jessica R |4 aut | |
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