Since the primary goal of CRyPTIC was to map the genetic variants in M. tuberculosis associated with resistance to different antibiotics, this genome-wide association study is one of the key research outputs of the project.
It brings together all the samples with genetic and drug susceptibility testing (DST) data and therefore relies on all the efforts to reduce the errors in the DST data, for example using AMyGDA to read the photographs of the 96-well plates and the efforts of the BashTheBug volunteers.
In addition to associating genes already known to confer resistance to specific antibiotics, putative resistance genes are proposed for each of the thirteen drugs on the UKMYC series of broth microdilution plates.
Danny Wilson and Sarah Earle led the GWAS analysis, which is complicated not only by the population structure (lineages) of M. tuberculosis but also by the fact that the resistance to each drug correlates with resistance to other drugs. Our involvement was mainly in improving the quality of the DST data, thereby improving the signal-to-noise ratio.
