Concordance of targeted and whole genome sequencing for Mycobacterium tuberculosis genotypic drug susceptibility testing

• DOI: 10.1016/j.diagmicrobio.2024.116249
• Publication Date: 2024-03-12T16:22:15Z
• Authors: William Cloutier ...; Marie-Sylvianne R...; Floriane Point; Astrid M. Knoblauch; Fanantenana Randr...; Michael B. Hall; Zamin Iqbal; Philip Supply; Anandi Martin; Niaina Rakotosami...; Simon Grandjean L...
• Keywords: INHA; Concordance; Amplicon

Targeted Next Generation Sequencing (tNGS) and Whole Genome (WGS) are increasingly used for genotypic drug susceptibility testing (gDST) of Mycobacterium tuberculosis. Thirty-two multi-drugs resistant 40 susceptible isolates from Madagascar were tested with Deeplex® Myc-TB WGS using the Mykrobe analysis pipeline. Sixty-four 72 (89%) yielded concordant categorical gDST results drugs by both assays. didn't detect pncA K96T, Q141P, H51P, H82R, rrs C517T rpsL K43R mutations, which identified as minority variants in corresponding tNGS. One discrepancy (rrs C517T) was associated insufficient sequencing depth on WGS. inhA G-154A isn't covered assay's amplification targets. Despite those targets being included assay, a T47A deletion gid not one isolate respectively. The evaluated tNGS assays show high but imperfect concordance.