These two papers, just published in PLoS Biology, are amongst the primary research outputs of the CRyPTIC project.

The first, entitled “A data compendium associating the genomes of 12,289 Mycobacterium tuberculosis isolates with quantitative resistance phenotypes to 13 antibiotics” describes in detail the large dataset of clinical tuberculosis isolates collected by CRyPTIC, including examining the probability of a sample being resistant to Drug B given it is resistant to Drug A (Fig. 4A).

The second paper, “Genome-wide association studies of global Mycobacterium tuberculosis resistance to 13 antimicrobials in 10,228 genomes identify new resistance mechanisms” uses all the data collected by CRyPTIC to investigate which genes associate with resistance to the 13 drugs tested using the UKMYC 96-well broth microdilution plates. This is difficult due to the population structure of M. tuberculosis and also correlations between different drugs due to treatment regimens. Putative new genetic variants were associated with resistance for all compounds, for example Rv1219c, which represses transcription of a multidrug efflux transport system encoded by Rv1217c-Rv1218c, is associated with resistance to isoniazid.