About the project
CRyPTIC aim to help improve control of tuberculosis and facilitate WHO’s End TB Strategy by better, faster and more targeted treatment of drug-resistant tuberculosis via genetic resistance prediction, paving the way towards universal drug susceptibility testing (DST).
Our ultimate goal is to achieve sufficiently accurate genetic prediction of resistance to most of the anti-tuberculosis drugs, so that whole genome sequencing replaces culture-based DST for TB. This will enable rapid-turnaround near-to-patient assays to revolutionise MDR-TB identification and management. This project is funded by MRC Newton Fund, Wellcome Trust, and Bill & Melinda Gates Foundation.
The development and validation of a high throughput 14-drug microtitre plate assay is a crucial component of CRyPTIC as a means to provide standardised quantitative minimum inhibitory concentrations (MIC) for drug-susceptibility phenotypes. The use of statistical methods to detect associations between robust and accurate MICs and genetic variants identified from whole genome sequencing (WGS) data of a large number of isolates will enable prediction models to accurately identify resistance-conferring genetic variants and to precisely quantify their contribution to the degree of drug resistance of an isolate.
We will assemble a global and clade-representative WGS collection to develop and use (i) better WGS assembly methods to identify more genomic variants with more precision, and (ii) improved statistical methods, both statistical genetic and machine learning, to detect associations between genetic variants and both quantitative and binary DST.