Whole Genome Sequencing

Tuberculosis (TB) actively infects more than 8 million people worldwide and causes over a million deaths each year.  In recent years, there has been an increase in the prevalence of drug resistant strains of tuberculosis, including multi-drug resistant (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB).  Drug resistance decreases the number of viable treatment options, resulting in a higher likelihood of a negative outcome. 

Current culture-based methods can take as long as 8 weeks to identify the drug resistance profile.  The Wadsworth Center Mycobacteriology Laboratory is developing a whole-genome sequencing (WGS) assay to identify members of the Mycobacterium tuberculosis complex (MTBC) and predict drug resistance from both clinical isolates and primary sputum samples.  A WGS assay using next generation sequencing (NGS) technologies has the capability of detecting every known mutation related to drug resistance, and can be completed more rapidly than culture-based drug susceptibility testing.  Although WGS has primarily been done on samples that are grown over a long period of time on solid media, we are exploring WGS on TB specimens directly from liquid media.  This approach will drastically reduce the amount of time it takes to generate a drug resistance profile.  A single WGS assay will be capable of replacing at least 5 pyrosequencing assays that are currently in use at the Wadsworth Center and may offer clinicians a more complete drug resistance profile than ever before.