Whole genome sequencing (WGS) is increasingly contributing to the clinical management of tuberculosis, but bioinformatic tools tailored for clinical reporting and suitable for accreditation to ISO standards are currently lacking. We developed tbtAMR, a flexible yet comprehensive tool for analysis of Mycobacterium tuberculosis genomic data, including inference of phenotypic susceptibility and lineage calling. Validation for accreditation was undertaken using 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. tbtAMR accurately predicted lineages and phenotypic susceptibility for first- and second-line drugs. We designed and developed a tool suitable for use in a clinical and public health laboratory, that can be tailored to specific laboratory needs by non-programmers. tbtAMR is now accredited to ISO standards and in routine use reporting AMR from WGS data in clinically relevant timeframe in Victoria. Report templates, validation methods and datasets are provided to offer a pathway for laboratories to adopt and seek their own accreditation for this critical test, to improve the management of tuberculosis globally.Competing Interest StatementThe authors have declared no competing interest.Footnotes* Revised to include new WHO catalogue of mutations.* https://github.com/MDU-PHL/tbtamr...

Bringing TB genomics to the clinic: A comprehensive pipeline to predict antimicrobial susceptibility from genomic data, validated and accredited to ISO standards

10.1101/2023.11.04.565651