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  6. Single Molecule-Overlapping Read (SMOR) Analysis for Minor Variant Mutation Detection in Pathogen Samples

Single Molecule-Overlapping Read (SMOR) Analysis for Minor Variant Mutation Detection in Pathogen Samples

Description

The technology uses single molecule-overlapping read (SMOR) analysis to detect the hetero-resistant population of a pathogen in a sample. The assay includes a pathogen such as Mycobacterium tuberculosis (TB) obtained from a sample (e.g., sputum). The nucleic acids are extracted from the sample and amplified based on the target genome. The target contains at least one minor variant associated with drug resistance in the pathogen. A consecutive sequencing process is implemented for overlapping nucleic acid strands from the targeted genome. Next, an alignment algorithm is applied to the sequencing data from the overlapping nucleic acid strands. Finally, an analysis of the aligned sequencing data is performed to detect at least one minor variant and hetero-resistant population of the pathogen.

Additional information

Patent number and inventor

US 10,508,311

Rebecca Colman, David Engelthaler, James Schupp, Paul Keim, and David Smith.

Potential applications

Clinical applications to detect and treat the hetero-resistant population of pathogens such as TB.

Benefits and advantages

Creating uncertainty in the diagnosis and treatment of TB, hetero-resistance is the simultaneous occurrence of drug-resistant subpopulations and drug-susceptible populations of bacteria.

The SMOR analysis detects drug-resistant subpopulations, consisting of 0.1 percent or less Mycobacteria tuberculosis, in under a week. In contrast, current technology uses phenotypic drug susceptibility testing with detection levels limited to one percent and requires 15-30 days to complete. By targeting antibiotic-resistant genes, the technology determines the actual mutation ratios in target loci, leading to increased hetero-resistance detection sensitivity and lower error bias. The overlapping reads allow for effective coverage of each locus on both strands of an individual sequenced DNA molecule, which in turn allows for independent confirmation of the specific nucleotide at that single locus.

The aim is to detect minor resistant variants and customize patient treatment for TB. The technology allows clinicians to follow the evolution of hetero-resistance, which is thought to drive multi-drug resistance in Mycobacterium tuberculosis, and determine its clinical relevance. Finally, clinicians can track patient treatment in a timely manner.

Case number and licensing status

2014-023

This invention is available for licensing.