Whole genome enrichment of Mycobacterium tuberculosis using CNERs

We developed a cost-effective method named Circular Nucleic acid Enrichment Reagent synthesis (CNERs) to generate whole-genome enrichment probes. We demonstrated the method by producing probes for Mycobacterium tuberculosis which we used to enrich M. tuberculosis DNA that had been spiked at concentrations as low as 0.01% and 100 genome copies against human DNA background to 1225-fold and 4636-fold. Further, we also enriched DNA from different M. tuberculosis lineages and M. bovis and demonstrated the utility of the WGE-CNERs data for lineage identification and drug-resistance characterization using an established pipeline. We conclude that our probe generation method for whole-genome enrichment will be a valuable tool for genomic epidemiology of emerging and difficult-to-grow pathogens.