Next-Generation Sequencing for Tuberculosis Detection: Insights from Findx Scientist

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Tonight, I watched a recording on the ONT YouTube channel. Swapna Uplekar, a Principal Scientist in Genomics and Sequencing at Findx presented the session, “Targeted next-generation sequencing for drug-resistant tuberculosis detection.”Uplekar works at Findx to use next-generation sequencing to develop diagnostics for diseases globally. Tuberculosis, Uplekar emphasized, remains the top killer, worsened by COVID-19. Drug-resistant cases often remain undiagnosed. Drug-resistant tuberculosis has evolved over the years from monoresistant to extensively resistant! Comprehensive drug susceptibility testing (DST) for TB is critical and can improve outcomes. Validating individual components for an end-to-end targeted tuberculosis sequencing (tNGS) solution is needed but complex and time-consuming. With the WHO, they have generated a TB knowledgebase and mutations catalog. The AmPORE-TB Oxford Nanopore Diagnostic was tested along with an Illumina-based approach for sequencing tuberculosis. The data generated in Seq&Treat studies helped evaluate these methods. Bacterial load and diagnostic accuracy were tested. Resistance to a panel of drugs was assessed, and most of the resistance was detected with the AmPORE-TB assay. The updated WHO recommendations now mention tNGS as an approach. Uplekar explained that they are now analyzing results from evaluating the updated AmPORE-TB assay and improved datasets. Uplekar ended by emphasizing policy changes are needed. Challenges include the need for specialized infrastructure and training to implement tNGS. Uplekar noted that tNGS is currently not intended to replace faster molecular diagnostics. The next phase of the Seq&Treat project is to help countries implement these approaches. Drug susceptibility testing (DST) methods are complicated for tuberculosis because of the organism’s slow growth rate. Whole genome sequencing of tuberculosis still works best with cultures that need time to grow. Thus, targeted approaches that offer speed, reliability, and sensitivity are needed. I now want to know more about the details of the AmPORE method.

How can targeted tuberculosis sequencing with Nanopore sequencing help facilitate drug sensitivity testing? AI-generated image.