Clinical use of whole genome sequencing for Mycobacterium tuberculosis

Abstract

Drug-resistant tuberculosis (TB) remains a major challenge to global health and to healthcare in the UK. In 2014, a total of 6,520 cases of TB were recorded in England, of which 1.4 % were multidrug-resistant TB (MDR-TB). Extensively drug-resistant TB (XDR-TB) occurs at a much lower rate, but the impact on the patient and hospital is severe. Current diagnostic methods such as drug susceptibility testing and targeted molecular tests are slow to return or examine only a limited number of target regions, respectively. Faster, more comprehensive diagnostics will enable earlier use of the most appropriate drug regimen, thus improving patient outcomes and reducing overall healthcare costs. Whole genome sequencing (WGS) has been shown to provide a rapid and comprehensive view of the genotype of the organism, and thus enable reliable prediction of the drug susceptibility phenotype within a clinically relevant timeframe. In addition, it provides the highest resolution when investigating transmission events in possible outbreak scenarios. However, robust software and database tools need to be developed for the full potential to be realized in this specialized area of medicine.

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…Whole-genome sequencing is complicated by the need for culture before DNA extraction, 147 incomplete knowledge of all resistance-conferring mutations, 59,148 and the need for a validated pipeline to accurately predict resistance. 149 A relational sequencing tuberculosis data platform (ReSeqTB) is being developed in a partnership between the Foundation for Innovative Diagnostics and Critical Path to TB Drug Regimens to catalogue genotypic and phenotypic data and to provide a validated pipeline for the analysis of whole-genome sequencing. However, in the absence of a complete understanding of the association between genotype and phenotype, whole-genome sequencing or targeted sequencing will remain a rule-in assay for the presence of resistance.…”

Comprehensive Whole-Genome Sequencing and Reporting of Drug Resistance Profiles on Clinical Cases of Mycobacterium tuberculosis in New York State

“…As tuberculosis treatment usually requires a multidrug regimen, an examination of many genes and genomic regions across the entire 4.4-Mb M. tuberculosis genome is necessary to generate the most comprehensive resistance profile, a feat that targeted molecular methods cannot achieve. Whole-genome sequencing (WGS) has recently been recognized as having the potential to improve diagnostics and reduce TAT to determine susceptibility to antituberculosis drugs in clinical cases (17)(18)(19).…”

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

“…Whole exome sequencing (WES) represents a significant breakthrough in clinical genetic as a powerful tool for etiological discovery in many kinds of disorders10. Benefited from the WES technology, a lot more pathogenic genes have been found and many types of diseases have been identified111213. Innovative application of new technologies is one of the major factors driving advances in medical science, most clinical applications of next-generation sequencing (NGS) concentrate on known and potential candidate genes to generate clear reports and finally promote clinical diagnosis1415161718.…”