CRyPTIC: cataloguing drug resistance mutations in M. tuberculosis

Drug resistance mutations in M. tuberculosis. Credit: Karen Arnott/EMBL-EBI.

CRyPTIC: cataloguing drug resistance mutations in M. tuberculosis

19 Oct 2021 - 13:01

Summary 

  • The CRyPTIC project has developed the world’s largest data resource for the study of drug resistance in tuberculosis (TB)
  • CRyPTIC is an international collaboration spanning 27 countries, that aims to find the causes of drug resistance in the bacteria that causes TB, and enable rapid diagnostics
  • Innovations by the CRyPTIC project promise a profound shift in how patients with TB are treated in the future

20 October 2021, Cambridge – In collaboration with colleagues across the world including EMBL’s European Bioinformatics Institute (EMBL-EBI), the Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC) project has generated the world’s largest data resource for the study of drug resistance in TB.

CRyPTIC aims to reveal the genetic causes of drug resistant TB to enable the development of DNA-based diagnostics. Using a new experimental assay, the consortium has semi-quantitatively measured the level of drug resistance and scanned the genome of over 15,000 Mycobacterium tuberculosis (M. tuberculosis) strains from across the globe.

Together these form a unique, rich dataset, which can be used to probe the genetic causes of drug resistance in TB. The end goal is to apply these insights to DNA-based diagnostics, predicting the drug resistance of a patient TB strain to different drugs allowing for personalised treatment.

These data are hosted at EMBL-EBI where they will be made freely available to the scientific community.

Access the CRyPTIC project data

Improving TB treatment

“TB currently causes over a million deaths per year all across the globe, and appropriate therapy is dependent on identifying which drugs will and won’t work for each patient’s particular infection”, said Zamin Iqbal, Group Leader at EMBL-EBI. “Determining the genetic basis of drug resistant TB enables rapid DNA-based diagnostics for identifying resistance to drugs, and informing therapy choice. By using quantitative measurements, rather than binary yes or no to resistance, we have been able to discern the fine-scale impact of specific mutations on resistance. In the process, this has generated a huge resource for science which we expect to be used for years to come”.

This work is detailed in nine new studies, covering a range of topics including:

  • new approaches to detecting genetic mutations in the M. tuberculosis genome
  • discovering the genetic causes of drug resistance and the precise impact of each mutation
  • how artificial intelligence can predict drug resistance from DNA signatures
  • how these data were used to build the new WHO TB resistance catalogue

You can find out more about this work in the preprints listed below. 

Find out more

Learn more in this press release published on the Oxford University website.

Funding

The CRyPTIC project is funded by the MRC Newton Fund, Wellcome, and the Bill and Melinda Gates Foundation.

Source articles

WALKER, T. M., (2021). The 2021 WHO Catalogue of Mycobacterium Tuberculosis Complex Mutations Associated with Drug Resistance: A New Global Standard for Molecular Diagnostics. Published online 21 09.

THE CRYPTIC CONSORTIUM. (2021). Genome-wide association studies of global Mycobacterium tuberculosis resistance to thirteen antimicrobials in 10,228 genomes. bioRxiv. Published online 16 09; DOI: 10.1101/2021.09.14.460272

THE CRYPTIC CONSORTIUM (2021). A generalisable approach to drug susceptibility prediction for M. Tuberculosis using machine learning and whole-genome sequencing. bioRxiv. Published online 16 09; DOI: 10.1101/2021.09.14.458035

THE CRYPTIC CONSORTIUM. (2021). Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach. bioRxiv. Published online 16 09; DOI: 10.1101/2021.09.14.460353

THE CRYPTIC CONSORTIUM. (2021). Epidemiological cutoff values for a 96-well broth microdilution plate for high-throughput research antibiotic susceptibility testing of M. tuberculosis. medRxiv. Published online 16 09; DOI: 10.1101/2021.02.24.21252386

BRANKIN, A., MALONE, K., et al. (2021). A data compendium of Mycobacterium tuberculosis antibiotic resistance. bioRxiv. Published online 16 09; DOI: 10.1101/2021.09.14.460274

FOWLER, P. W., et al. (2021). BashTheBug: a crowd of volunteers reproducibly and accurately measure the minimum inhibitory concentrations of 13 antitubercular drugs from photographs of 96-well broth microdilution plates. bioRxiv. Published online 13 09; DOI: 10.1101/2021.07.20.453060

HUNT, M., et al. (2021). Minos: variant adjudication and joint genotyping of cohorts of bacterial genomes. bioRxiv. Published online 15 09; DOI: 10.1101/2021.09.15.460475

SONNENKALB, L., et al. (2021). Deciphering Bedaquiline and Clofazimine Resistance in Tuberculosis: An Evolutionary Medicine Approach. bioRxiv. Published online 13 09; DOI: 10.1101/2021.03.19.436148

Contact the news team

Vicky Hatch | Communications Officer

vhatch@ebi.ac.uk

Oana Stroe | Senior Communications Officer

stroe@ebi.ac.uk

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