Detection of low-level mixed-population drug resistance in Mycobacterium tuberculosis using high fidelity amplicon sequencing. Mycobacterium tuberculosis

The study's goal was to describe the method of “single molecule-overlapping reads” (SMOR) analysis with next generation ligation-free amplicon sequencing for determination of ultra-rare target alleles in complex mixtures that provides an increased sensitivity over standard DNA sequencing. The method was described using standardized mixtures of DNA from resistant and susceptible Mycobacterium tuberculosis isolates and the assay’s performance for detecting ultra-rare drug resistance subpopulations in DNA extracted directly from clinical sputum samples.