Bringing tuberculosis genomics to the clinic: development and validation of a comprehensive pipeline to predict antimicrobial susceptibility from genomic data, accredited to ISO standards

Updated

Although the availability of bioinformatics tools for analysis and clinical reporting of Mycobacterium tuberculosis sequence data is improving, there remains a need for accessible, flexible bioinformatics tools that can be easily tailored for clinical reporting needs in different settings and that are suitable for accreditation to international standards.

We developed tbtAMR, a flexible yet comprehensive data-driven tool for analysis of M. tuberculosis genomic data.

tbtAMR takes short-read sequencing data (fastq files) or an annotated vcf file (from short-read or long-read sequencing), maps genomic variants (single nucleotide polymorphisms, insertions or deletions, large structural changes, and gene loss or loss of function), identifies resistance-associated mutations from the WHO catalogue (or user-defined database), and interprets and classifies drug resistance to produce an output file ready for clinical reporting.

tbtAMR accurately predicted lineages and phenotypic susceptibility for first-line (sensitivity 94.6% [95% CI 94.2-95.0], specificity 97.5% [97.3-97.7]) and second-line (sensitivity 83.7% [82.7-84.7], specificity 98.0% [97.9-98.1]) drugs.

We have accredited this tool to ISO standards in our laboratory, and it has been implemented for routine reporting of antimicrobial resistance from genomic sequence data in a clinically relevant timeframe.

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