Genomic Sequencing from Sputum for Tuberculosis Disease Diagnosis, Lineage Determination and Drug Susceptibility Prediction

Although targeted next generation sequencing (tNGS) has been developed to identify species, lineage, predict drug susceptibility, and inform on spoligotype, it is inherently restricted in its resolution in comparative genomics for outbreak investigations when compared to WGS. WGS therefore remains the ultimate goal. Here we explore how close we can get to obtaining useful diagnostic information from sequencing primary clinical samples in two high-burden settings; Madagascar, a low-income country, and India, a middle-income country. We present data on samples with a range of bacillary loads, sequenced on both laboratory-confined (Illumina) and portable (Oxford Nanopore Technologies, (ONT)) sequencing platforms to assess how close we are to implementing culture-free sequencing protocols into the clinical space what could critically reduce TB diagnostics turnaround times.