Next Generation Sequencing: Opportunities and Challenges in Tuberculosis Research

Despite a reasonable reduction in tuberculosis incidence and mortality in the last few years, the disease remains to be the major global public health challenge. The advent and transmission of drug-resistant tuberculosis (DR-TB) and delayed diagnosis and treatment have further worsened the control efforts against tuberculosis. The current culture- and PCR-based diagnostic methods are not sufficiently rapid and accurate enough to efficiently manage the patient load. While next generation molecular diagnostic assays such as the Xpert MTB/RIF and line probe assays (MTBDRplus and MTBDRsl) can only detect resistance-conferring mutations in specific target regions and miss novel emerging loci associated with resistance. Recent advancements in next generation sequencing (NGS) platforms and development of cost-efficient workflows have equipped the field with diagnostic tools that not only can detect existing mutations associated with drug resistance but can also identify newer coordinates of drug resistance. In a very short time frame, NGS provides whole genome sequence at a fairly low cost, that too without the need of culture (i.e., directly from the clinical specimen). NGS holds enormous potential as a tool for guiding personalized treatment through precision medicine as well as epidemiological monitoring of tuberculosis. In order to augment the accuracy and shorten the time taken to the accurate diagnosis of tuberculosis, NGS can become an unprecedented technology for diagnosis as well as epidemiological investigations of tuberculosis. In the present chapter, we will be discussing the available platforms, workflows, and tools based on NGS technology for the diagnosis and monitoring of tuberculosis.