Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CRyPTIC)

Lead Research Organisation: University of Oxford
Department Name: UNLISTED

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Technical Summary

Our aim is to achieve sufficiently accurate genetic prediction of resistance to all anti-tuberculosis
drugs for whole genome sequencing (WGS) to replace slow, cumbersome, culture-based drug
susceptibility testing (DST) for Mycobacterium tuberculosis complex (MTBC). This would enable
rapid-turnaround near-to-patient assays to revolutionize drug-resistant TB identification and
management.

This multidisciplinary collaboration including TB experts from five continents, WHO,
statisticians/mathematicians and software engineers will integrate machine-learning, statistical
genetics and molecular genetics methods to uncover all genomic variation causing at least 1%
resistance to first- and second-line anti-TB drugs with >1% resistance prevalence. We will use largescale
global and clade-representative WGS (>90,000), with initially >37,000 isolates with extended DST. Approaches include better WGS assembly to identify more variants with more precision,
improved statistical methods to detect associations between variants and DST, and selected
molecular validation of predicted resistant variants.

The project will create an automatically-updating, free, publically accessible, comprehensive data
repository of resistance-conferring variants. This will provide accurate genetic resistance prediction
for all drugs for any new MTBC WGS; superior design of near-to-patient amplification-based
molecular drug-resistance tests as alternatives to ‘WGS-only’ solutions; and better, faster and more
targeted drug-resistant TB treatment, facilitating improved control and WHO’s initiative to eliminate
TB by 2050.

Organisations

People

ORCID iD

Publications

10 25 50

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CRyPTIC Consortium And The 100,000 Genomes Project (2018) Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing. in The New England journal of medicine

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Donovan J (2020) Xpert MTB/RIF Ultra for the Diagnosis of Tuberculous Meningitis: A Small Step Forward. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Grobbel HP (2021) Design of Multidrug-Resistant Tuberculosis Treatment Regimens Based on DNA Sequencing. in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

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Kouchaki S (2019) Application of machine learning techniques to tuberculosis drug resistance analysis. in Bioinformatics (Oxford, England)

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Liu D (2022) Whole-genome sequencing for surveillance of tuberculosis drug resistance and determination of resistance level in China. in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases

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Yang Y (2019) DeepAMR for predicting co-occurrent resistance of Mycobacterium tuberculosis. in Bioinformatics (Oxford, England)

 
Title Susceptible by Anna Dumitriu 
Description Artist in Residence Anna Dumitriu has created a data-driven interactive digital artwork based on research from the CRyPTIC project. 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2020 
Impact A video version of Susceptible has been featured in 3 international exhibitions: - Neural Network Apophenia as part of the EVERART Festival in Moscow, Russia (3rd July and 3rd August 2020) - EFECT DE LA MICRO LA MACRO as part of Quantum Questions 2020 in Cluj-Napoca, Romania (24th November to 12th December 2020) - Artificio at the Museo Bolivariano De Arte Contemporaneo in Santa Marta, Colombia (20th October 2021 - on going) 
URL https://annadumitriu.co.uk/portfolio/susceptible/
 
Description Better predicting TB antituberculosis drug resistance and used by diagnostic tests
First Year Of Impact 2022
Sector Healthcare
Impact Types Policy & public services

 
Description The WHO TB mutation catalogue
Geographic Reach Multiple continents/international 
Policy Influence Type Citation in other policy documents
Impact The impacts have been as follows; 1. Provides a systematic knowledge base for determining genomic susceptibility of TB to anti-tuberculosis drugs 2. This is used to guide improved rapid diagnostic tests supported by the World Health Organisation (WHO) 3. Provides improved resistance prediction for genome sequencing diagnostic results 4. Strengthens personalised treatment of multiresistant TB 5. Simplifies and improves patient management pathways for TB 6. Lilley to improve outcomes in the treatment of TB
URL https://www.who.int/publications/i/item/9789240028173
 
Description Enriching Engagement - broadening and deepening public participation in BashTheBug.net
Amount £20,429 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2019 
End 09/2020
 
Description Establishing a statistically confidence-graded catalogue of TB mutations catalogue for WHO review
Amount $112,731 (USD)
Organisation Foundation for Innovative New Diagnostics (FIND) 
Sector Charity/Non Profit
Country Switzerland
Start 01/2020 
End 07/2021
 
Description HPRU HAI and AMR
Amount £5,761,932 (GBP)
Funding ID NIHR200915 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2020 
End 03/2025
 
Description Innovations' Innovator award, SP3: Scalable Software for Pathogen Reads to Clinical Research using Next Generation Sequencing
Amount £1,029,833 (GBP)
Funding ID 215800/Z/19/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2020 
End 02/2022
 
Title Pipeline developed to analyse TB WGS including SNPs and indels 
Description A pipeline has been developed improving existing pipelines to identify both SNPs and Indels in TB WGS., 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? No  
Impact None yet 
 
Title CRyPTIC Resistance Prediction catalogue 
Description Catalogue outlining the Mtb resistance-conferring mutations for antimicrobial drugs based on existing literature and publications. 
Type Of Material Computer model/algorithm 
Year Produced 2019 
Provided To Others? Yes  
Impact No impact yet, but has been passed others in similar fields to compare to their own catalogue. 
 
Title CliRes database hosted at OUCRU to collect DST and epidemiological data from across the world 
Description A database hosted at Oxford University Clinical Research Unit which allows all sites acros the world to record DST results and epidemiological data relating to the patients and isolates which can be accessed by the analyses team. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact ability to record data from all sites in a formatted way to allow analyses team to systematically align WGS with DST data 
 
Title Data collection of Mtb whole genome sequences and metadata 
Description Dataset of approximately 15,000 Mtb whole geneome sequences and metadata (phenotype data) from across the world to contibute the CRyPTIC dataset. 
Type Of Material Database/Collection of data 
Year Produced 2020 
Provided To Others? No  
Impact Contributes to the CRyPTIC dataset 
 
Title MTB WGS database 
Description A database containing approximately 55,000 Mtb Whole Genome sequences and variant calling from participating sites across the world and downloaded from ENA 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? No  
Impact Generation of the Mtb Resistance prediction catalogue and provides a dataset for validation. 
 
Description China CDC collaboration 
Organisation Chinese Center for Disease Control and Prevention (China CDC)
Country China 
Sector Public 
PI Contribution Coordination of project and analyses of DST and WGS from approximately 100,000 clinical TB isolates across the world to determine whether antimicrobial resistance can be predicted through whole genome sequencing.
Collaborator Contribution Contribute ~3100 WGS and DST from TB clinical isolates. Contibute to the analyses of the data and help identify further research questions and opportunties arising from the dataset. Member of the General Assembly
Impact No outcome as yet, project just started.
Start Year 2016
 
Description Collaboration Aldolfo Lutz 
Organisation Instituto Adolfo Lutz
Country Brazil 
Sector Public 
PI Contribution Co-ordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical isoaltes across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution Contribute DST and WGS from 400 TB isolates. Contibute to analyses and help identify research opportunities and questions from dataset. Member of the general assembly
Impact None, project just started
Start Year 2016
 
Description Collaboration CPTR 
Organisation Critical Path to TB Drug Regimens (CPTR)
Country United States 
Sector Public 
PI Contribution Co-ordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS.
Collaborator Contribution Assistance with co-ordination at the start of project. Financial assistance to sequence 1000 TB genomes Work closely on data interoperability with regards to TB
Impact None, project just started
Start Year 2016
 
Description Collaboration EBI 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution co-ordination ofthe project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted from WGS.
Collaborator Contribution Co-applicant Zamin Iqbal has moved to EBI. EBI will be developing and and hosting the "data warehouse" allowing the upload of sequences generated across the world for view initially by the research team and them open access. Will be developing variant calling software for the sequences.
Impact None, project just started.
Start Year 2017
 
Description Collaboration Janssen 
Organisation Janssen Pharmaceutica NV
Country Belgium 
Sector Private 
PI Contribution Co-ordination of project and analyse of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution Provide research service to allow bedaquiline testing in Taiwan using microtitre plates. Provide bedaquiline for inclusion of the CRyPTIC generated DST plates. Provide general advice regarding microtitre DST and bedaquiline.
Impact Microtitre DST plate for use under CRyPTIC project
Start Year 2016
 
Description Collaboration NICD 
Organisation Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases, National Health Laboratory Service in Johannesburg
Country South Africa 
Sector Hospitals 
PI Contribution Coodination of project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution Contribute WGS and DST from 2300 TB clinical isolates. Contribute to the analyses and help identify further research opportunities and questions arising from the data. Member of the General Assembly
Impact No output, project just started
Start Year 2016
 
Description Collaboration with AHRI 
Organisation Africa Health Research Institute
Country South Africa 
Sector Charity/Non Profit 
PI Contribution Building of a Mtb resistance prediction catalogue by running 10,000s Mtb sequences through the CRyPTIC variant calling pipeline and identifying rare resistance conferring variants. Sharing the catalogue with the community. Providing support for clinical outcome analyses of drug resistant Mtb
Collaborator Contribution Providing 100 WGS, extensive phenotype data and clinical data for MDR-Mtb.
Impact No output
Start Year 2018
 
Description Collaboration with AHRI 
Organisation University of Liverpool
Country United Kingdom 
Sector Academic/University 
PI Contribution Building of a Mtb resistance prediction catalogue by running 10,000s Mtb sequences through the CRyPTIC variant calling pipeline and identifying rare resistance conferring variants. Sharing the catalogue with the community. Providing support for clinical outcome analyses of drug resistant Mtb
Collaborator Contribution Providing 100 WGS, extensive phenotype data and clinical data for MDR-Mtb.
Impact No output
Start Year 2018
 
Description Collaboration with Atlanta CDC 
Organisation Centers for Disease Control and Prevention (CDC)
Country United States 
Sector Public 
PI Contribution Co-ordination of project and analyses of DST and WGS from approximately 100,000 TB Clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution validation of novel gene variants conferring resistance to antimicrobials. Member of the General Assembly
Impact No outputs, project just started.
Start Year 2016
 
Description Collaboration with Bhutan 
Organisation Royal Centre for Disease Control
Country Bhutan 
Sector Academic/University 
PI Contribution Building a Mtb resistance prediction catalogue by running 10,000s of Mtb WGS thought a variant calling pipeline and identifying rare resistance-conferring variants. Sharing the catalogue with the community
Collaborator Contribution Contributing 1000 Mtb WGS and phenotype data
Impact No output
Start Year 2018
 
Description Collaboration with Emory 
Organisation Emory University
Country United States 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donation of Mtb sequences and phenotypes
Impact None yet
Start Year 2020
 
Description Collaboration with Germany 
Organisation Borstel Research Centre
Country Germany 
Sector Private 
PI Contribution Co-ordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical isolates across the world to determine whether antimicrobial resistacnce can be predicted through WGS.
Collaborator Contribution Contribute WGS and DST from 2000 TB clinical isolates. Contribute to analyses and help identify further research questions from dataset. Members of the General Assembly
Impact No output, project just started.
Start Year 2016
 
Description Collaboration with Germany 
Organisation IML red GmbH
Department Institute of Microbiology and Laboratory Medicine
Country Germany 
Sector Learned Society 
PI Contribution Co-ordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical isolates across the world to determine whether antimicrobial resistacnce can be predicted through WGS.
Collaborator Contribution Contribute WGS and DST from 2000 TB clinical isolates. Contribute to analyses and help identify further research questions from dataset. Members of the General Assembly
Impact No output, project just started.
Start Year 2016
 
Description Collaboration with Harvard 
Organisation Harvard University
Department Harvard Medical School
Country United States 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donation of Mtb sequence and phenotype data
Impact None yet
Start Year 2020
 
Description Collaboration with IPM 
Organisation Pasteur Institute of Madagascar
Country Madagascar 
Sector Academic/University 
PI Contribution Building a Mtb resistance prediction catalogue by running 10,000s of Mtb sequences from across the world through the CRyPTIC variant calling pipeline and identifying rare variants. Sharing knowledge with the community.
Collaborator Contribution Contributing 668 Mtb WGS and phenotype data to the project
Impact No outcome yet
Start Year 2018
 
Description Collaboration with Monash 
Organisation Monash University
Country Australia 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donation of Mtb sequences and phenotypes
Impact None yet
Start Year 2020
 
Description Collaboration with National University of Singapore 
Organisation National University of Singapore
Country Singapore 
Sector Academic/University 
PI Contribution Analyses of WGS and DST data from samples collected as part of clinical trial in Philippines
Collaborator Contribution Contribution of WGS and DST data from samples collected as part of clinical trail in Philliipines. Funding provided by collaborator.
Impact No outputs yet
Start Year 2017
 
Description Collaboration with Ontario 
Organisation Public Health Ontario
Country Canada 
Sector Hospitals 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donate Mtb Sequence and metadata
Impact None yet
Start Year 2020
 
Description Collaboration with Otsuka 
Organisation Otsuka Pharmaceutical
Country Japan 
Sector Private 
PI Contribution Coordination of project and analses of DST and WGS from approximately 100,000 TB clinical samples from across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution provided Delamind for the microtitre DST plates used under the project which is not commercially available.
Impact Microtitre plate containing delamanid manufactured by Thermofisher for research use only.
Start Year 2016
 
Description Collaboration with PHW 
Organisation Public Health Wales NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donate Mtb sequences and phenotype data
Impact None yet
Start Year 2019
 
Description Collaboration with Public Health Sweden 
Organisation Stockholm University
Department Public Health
Country Sweden 
Sector Academic/University 
PI Contribution Analyses of the WGS and DST data generated on clinical isolates from Sweden as part of the CRyPTIC objectives.
Collaborator Contribution Contibution of DST and DST data generated from clinical isolates.
Impact No outputs to date
Start Year 2017
 
Description Collaboration with SRI 
Organisation San Raffaele Hospital
Country Italy 
Sector Hospitals 
PI Contribution Co-ordination of project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution Contribute to WGS and DST from 2000 clinical isolates. Contribute to the analyses and help identify further research quesitons and opportunity from data. Member of the General Assembly
Impact No output, project just started.
Start Year 2016
 
Description Collaboration with South Africa 
Organisation Wits Health Consortium
Country South Africa 
Sector Private 
PI Contribution Co-ordination of the project and analyses of DST and WGS fro approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution Legal entity for National Institute of Communicable Diseases, Johannesberg, South Africa
Impact No output yet, project only just started.
Start Year 2016
 
Description Collaboration with Swisstph 
Organisation Swiss Tropical & Public Health Institute
Country Switzerland 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donation of Mtb sequences and phenotypes
Impact None yet
Start Year 2020
 
Description Collaboration with Taiwan 
Organisation Centers for Disease Control Taiwan
Country Taiwan, Province of China 
Sector Public 
PI Contribution Analyses DST and WGS data of clinical isolates from Taiwan as part of worldwide dataset
Collaborator Contribution Contributing DST and WGS data from Taiwan
Impact No output yet
Start Year 2017
 
Description Collaboration with Torch consortium 
Organisation University of Antwerp
Country Belgium 
Sector Academic/University 
PI Contribution building a Mtb resistance prediction catalogue by running 10,000s of Mtb sequences through the variant calling pipeline and identifying rare variants conferring resistance. Sharing the catalogue with the community. Providing support with secondary projects using the data, such as machine learning.
Collaborator Contribution Contributing ~1200 Mtb and phenotype data to the cryptic consortium
Impact None yet
Start Year 2018
 
Description Collaboration with Torch consortium 
Organisation University of Stellenbosch
Country South Africa 
Sector Academic/University 
PI Contribution building a Mtb resistance prediction catalogue by running 10,000s of Mtb sequences through the variant calling pipeline and identifying rare variants conferring resistance. Sharing the catalogue with the community. Providing support with secondary projects using the data, such as machine learning.
Collaborator Contribution Contributing ~1200 Mtb and phenotype data to the cryptic consortium
Impact None yet
Start Year 2018
 
Description Collaboration with Trinity College Dublin 
Organisation Trinity College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donation of Mtb sequence and phenotype data
Impact None yet
Start Year 2020
 
Description Collaboration with UCSF 
Organisation University of California, San Francisco
Department School of Medicine (UCSF)
Country United States 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution Donate Mtb sequences and phenotype data.
Impact None yet
Start Year 2020
 
Description Collaboration with Uni Peruana Cayetano Heredia 
Organisation Cayetano Heredia University
Country Peru 
Sector Academic/University 
PI Contribution Co-ordination of project and analyses of DAT and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution Contribute 3100 WGS and DST data from TB clinical isolates. Contibute to analyses and help identify further research opportunities and questions arising from the dataset.
Impact None as yet as project just started.
Start Year 2016
 
Description Collaboration with Wadsworth 
Organisation Wadsworth Center
Country United States 
Sector Public 
PI Contribution Building a Mtb resistance prediction catalogue by running 10,000s of Mtb sequences through the variant calling pipeline and identifying rare reistance conferring mutations. Sharing the catalogue with the community.
Collaborator Contribution Contribution of Mtb 780 WGS and phenotype data
Impact No output
Start Year 2018
 
Description Collaboration with Yale 
Organisation Yale University
Country United States 
Sector Academic/University 
PI Contribution Building a Mtb resistance prediction catalogue by running 10,000s of Mtb WGS though the variant calling pipeline and identifying rare resistance conferring mutations. Sharing the cataogue with the community
Collaborator Contribution Contribution of 500 MTb WGS and Phenoptye data
Impact No output
Start Year 2018
 
Description Collaboration with sites providing existing data and advisors 
Organisation Imperial College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Co-ordination of the project and analyses of WGS and DST from approximately 100,000 TB clinical isolates across the world to determine whether antimicrobial resistance can be predicted through whole genome sequencing
Collaborator Contribution Contibution of existing WGS and DST from TB isolates. Contribution to analyses and help identify further research questions from the dataset. Members of the General Assembly
Impact None, project just started
Start Year 2016
 
Description Collaboration with sites providing existing data and advisors 
Organisation NHS Lothian
Country United Kingdom 
Sector Public 
PI Contribution Co-ordination of the project and analyses of WGS and DST from approximately 100,000 TB clinical isolates across the world to determine whether antimicrobial resistance can be predicted through whole genome sequencing
Collaborator Contribution Contibution of existing WGS and DST from TB isolates. Contribution to analyses and help identify further research questions from the dataset. Members of the General Assembly
Impact None, project just started
Start Year 2016
 
Description Collaboration with sites providing existing data and advisors 
Organisation University of British Columbia
Country Canada 
Sector Academic/University 
PI Contribution Co-ordination of the project and analyses of WGS and DST from approximately 100,000 TB clinical isolates across the world to determine whether antimicrobial resistance can be predicted through whole genome sequencing
Collaborator Contribution Contibution of existing WGS and DST from TB isolates. Contribution to analyses and help identify further research questions from the dataset. Members of the General Assembly
Impact None, project just started
Start Year 2016
 
Description Collaboration with sites providing existing data and advisors 
Organisation University of Cape Town
Country South Africa 
Sector Academic/University 
PI Contribution Co-ordination of the project and analyses of WGS and DST from approximately 100,000 TB clinical isolates across the world to determine whether antimicrobial resistance can be predicted through whole genome sequencing
Collaborator Contribution Contibution of existing WGS and DST from TB isolates. Contribution to analyses and help identify further research questions from the dataset. Members of the General Assembly
Impact None, project just started
Start Year 2016
 
Description Collaboration with the Netherlands Public Health RIVM 
Organisation National Institute for Public Health and Environment (RIVM)
Country Netherlands 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution donate Mtb Sequences and phenotype
Impact None yet
Start Year 2020
 
Description External Advisory Board 
Organisation Foundation for Innovative New Diagnostics (FIND)
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution Coordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution External Advisory Board i) providing advice on resolution of problems identified by the Executive Committee; and ii) reviewing and monitoring overall progress of the project and providing advice to the Executive Committee with regards to achieving deliverables; and iii) providing strategic oversight of effective dissemination, publication and deployment of project aims and outputs.
Impact No output project just started.
Start Year 2016
 
Description External Advisory Board 
Organisation Indian Council of Medical Research (ICMR)
Country India 
Sector Public 
PI Contribution Coordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution External Advisory Board i) providing advice on resolution of problems identified by the Executive Committee; and ii) reviewing and monitoring overall progress of the project and providing advice to the Executive Committee with regards to achieving deliverables; and iii) providing strategic oversight of effective dissemination, publication and deployment of project aims and outputs.
Impact No output project just started.
Start Year 2016
 
Description External Advisory Board 
Organisation University of Lille
Country France 
Sector Academic/University 
PI Contribution Coordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution External Advisory Board i) providing advice on resolution of problems identified by the Executive Committee; and ii) reviewing and monitoring overall progress of the project and providing advice to the Executive Committee with regards to achieving deliverables; and iii) providing strategic oversight of effective dissemination, publication and deployment of project aims and outputs.
Impact No output project just started.
Start Year 2016
 
Description External Advisory Board 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution Coordination of the project and analyses of DST and WGS from approximately 100,000 TB clinical samples across the world to determine whether antimicrobial resistance can be predicted through WGS
Collaborator Contribution External Advisory Board i) providing advice on resolution of problems identified by the Executive Committee; and ii) reviewing and monitoring overall progress of the project and providing advice to the Executive Committee with regards to achieving deliverables; and iii) providing strategic oversight of effective dissemination, publication and deployment of project aims and outputs.
Impact No output project just started.
Start Year 2016
 
Description FIND/WHO collaboration 
Organisation Foundation for Innovative New Diagnostics (FIND)
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution - Provide a catalogue of variants conferring anti-tuberculosis drug resistance classified by strength of supporting statistical evidence - Provide a working cloud based whole genome sequence analysis pipeline for FASTQ processing, variant calling, resistance prediction and cluster analysis in World Health Organisation AWS environment - Provide working STATA analysis code for analysis of the combined genomic and phenotypic data quantifying the association between DR mutations and phenotypic resistance yielding LRs and ORs in WHO AWS environment - Complete transfer of all genotypic and phenotypic data used for creation of mutation catalogue to WHO AWS environment
Collaborator Contribution Provided funding and intellectual input and support delivery of the objectives. Facilitated access to additional WGS datasets to allow further building of drug resistance prediction catalogue.
Impact No outcomes yet, grant is still active.
Start Year 2020
 
Description FMR Collaboration 
Organisation Fidelity Management & Research
Country India 
Sector Private 
PI Contribution Lead institution contributing to analysis of the TB WGS and DST results from the project
Collaborator Contribution Providing ~6000 WGS on TB clinical samples and some DST results. Contribute to analyses and help identify research questions from dataset. Member of the General Assembly
Impact The project has just started, DNA extracted from clinical TB samples and sent for sequencing. PZA DST results generated by FMR
Start Year 2016
 
Description Hinduja Hosp Collaboration 
Organisation P. D. Hinduja Hospital and Medical Research Centre
Country India 
Sector Hospitals 
PI Contribution Lead Insitution, coordinator and analyses of WGS and DST from TB clinical samples across the world.
Collaborator Contribution Will provide DST information on ~6000 clinical TB isolates. Contribute to analyses and help identify further research questions from data. Member of the General Assembly
Impact None yet, project just started.
Start Year 2016
 
Description PacBio sequencing 
Organisation Icahn School of Medicine at Mount Sinai
Country United States 
Sector Academic/University 
PI Contribution Investigation of plasmid structure
Collaborator Contribution Sequencing and analysis Member of the CRyPTIC General Assembly. Member of REHAB Steering Committee
Impact Two publications
Start Year 2014
 
Description Provision of Pretomanid by TB alliance 
Organisation The Global Alliance for TB Drug Development
Country Global 
Sector Private 
PI Contribution Provided evidence for the use of a microtitre plate for dried antibiotics as a method of phenotyping Mtb isolates
Collaborator Contribution Providing pretonamid drug on a microtitre plate intended to be available commercially.
Impact None yet
Start Year 2019
 
Description Public Health England (PHE) 
Organisation Public Health England
Country United Kingdom 
Sector Public 
PI Contribution Access to sequencing data and research results.
Collaborator Contribution Access to S. aureus, Norovirus, C. difficile and TB samples and related epidemiological data. Staff to collect the samples and data and to ship this to Oxford and the Wellcome Trust Sanger Institute for sequencing. As well as intellectual input into the research. Member of REHAB Steering Committee
Impact Successful translation of next generation sequencing into public health microbiology
Start Year 2009
 
Description World Health Organisation contribution of data 
Organisation World Health Organization (WHO)
Country Global 
Sector Public 
PI Contribution Building a resistance prediction catalogue by running 10000s of Mtb sequences though pathogen variant calling pipeline, identifying rare variants and sharing with the community.
Collaborator Contribution Provided Mtb WGS and phenotype data from around 3000 isolates from drug surveillance project
Impact Contribution of resistance conferring mutations to the CRyPTIC resistance calling catalogue.
Start Year 2018
 
Description collaboration with LSHTM 
Organisation London School of Hygiene and Tropical Medicine (LSHTM)
Department Malaria Centre
Country United Kingdom 
Sector Academic/University 
PI Contribution Coordination of project and analyses of DST and WGS from approximately 100,000 WGS TB clinical isolates. across the world to determine whether antimicrobial resisatnce can be predicted through WGS.
Collaborator Contribution Subcontracting to Universidad Peruana Cayetano Heredia. Member of the General Assembly
Impact No output as yet as project just started.
Start Year 2016
 
Description collaboration with University of Sydney 
Organisation University of Sydney
Country Australia 
Sector Academic/University 
PI Contribution Provide analysis of a large Mtb sequence and phenotype dataset
Collaborator Contribution donation of Mtb sequences and phenotypes
Impact None yet
Start Year 2020
 
Title AMyGDA -Automated Detection of Bacterial Growth on 96-well plates (AMyGDA) 
Description This software automatically identifies whether there is Mtb growth in each well of a 96 well plate containing a range of anti-microbials to establish the minimum inhibitory concentration per drug for each isolate using plate images taken by Vizion (from Thermofisher). As the project progresses, we will be using this as a method of quality control and will re-evaluate any plates where the manual MIC reading for any drug has more than 1 doubling dilution difference to determine reading errors. Additionally, this software can be expanded to other plates and other drugs for other bacteria so is transferrable. 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2017
Licensed Yes
Impact Currently being considered by thermofisher to use with Vizion software instead of manually reading plates. Incorporated in CRyPTIC workflow to assign confidence in the MIC readings.
 
Title Piezo 
Description Software which considers variant calling files from WGS pipeline Clockwork and applies a genetic resistance prediction catalogue to output predicted phenotype for 12 anti-tuberculosis drugs 
IP Reference  
Protection Copyrighted (e.g. software)
Year Protection Granted 2019
Licensed No
Impact None as yet.
 
Title 13 drug anti-microbial microtitre plate 
Description 13 anti-microbial microtitre plate allows extensive phenotypic quantiative characterisation of a Mtb isolate using one cheap assay. The plates have been designed by the CRyPTIC team and manufactured by Thermofisher as a standard service, paid for from the CRyPTIC grant. We are currently seeking endorsement for the plate as a Mtb diagnostic tool from the World Health Organisation. It is only available to members of CRyPTIC in accordance with agreements in place with Otsuka and Janssen, we anticipate endorsement will lead to the plates being available to researchers and clinicians outside the project. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact No impact yet. 
 
Title Piezo software 
Description Software which considers variant calling files generated from Clockwork pipeline and the genetics resistance calling catalogue and provides a predicted phenotype output for 13 different drugs. 
Type Of Technology Software 
Year Produced 2019 
Impact Allows swift phenotype prediction from the WGS files for CRyPTIC whole genome sequences. 
 
Title Software to automatically read CRyPTIC anti-tuberculosis microtitre plate (CRyPTIC_DST) 
Description One goal of CRyPTIC is to pursue a validation for regulatory approval of 96 well microtitre pates developed under CRyPTIC (UKMYC5 plates; Trek Sensititre manufactured in collaboration with Thermo Fisher) offering standardized minimum inhibitory concentrations (MIC) for 14 anti-tuberculosis drugs. Seven CRyPTIC collaborators across the world have performed intitial evaluation of this microtitre plate by performing extensive DST on a laboratory-adapted H37Rv MTBC strain followed by evaluation of a panel of well characterized drug resistant strains which were shipped for simultaneous testing by all sites. This initial evaluation involved reading the plates by three different methods: Inverted microscope, mirrored plate reader and Sensititre™ Vizion™ Digital MIC Viewing System (Vizion). Vizion allows the user to capture images which are analysed by the team in Oxford, however, all three methods of reading are subject to user interpretation which is likely to be dependent on experience reading anti-tuberculosis microtitre plates. CRyPTIC_DST is a Python module that analyses photographs of 96 well plates and determines the growth of bacteria in each well. Since each well contains a different concentration of antibiotic and there are 14 antibiotics on the plate, this data can be used to determine the minimum inhibitory concentrations of each antibiotic and hence the drug susceptibility profile of the M.tuberculosis pathogen. The code maintains a local copy of all the metadata for each plate locally in a filesystem-based tree, stored in JSON files. Data and image are automatically downloaded from the CRyPTIC SQL database using its WebService, thereby bypassing the browser. The photograph of each plate is first cleaned up by applying a mean shift algorithm and locally equalising the histograms. The code then iteratively searches for circles in the image using a Hough transform and stops if and only if 96 circles of approximately the correct radius are found. This defines the locations of the wells. A square of pixels in the middle of each well is analysed; specifically the proportion of pixels below a threshold are counted, and if there are sufficient, the well is classified as containing growth. Since the metadata are also stored locally, the results of the image algorithm can be directly compared to the human measurements. The code can be run on a consumer grade laptop and each image takes around 5 seconds to analyse. It is currently stored as a private GitHub repository and will be made public upon publication of the first CRyPTIC validation paper. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2017 
Impact This has only just been developed and is currently being tested. Impact of this could minimise interlab and intralab variation of microtitre plate readings due and allow MIC determination irrespective of user experience 
 
Description Bacterial world - Oxford Natural History Museum 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Showcasing Bash the Bug and encouraging particpation.
Year(s) Of Engagement Activity 2018,2019
URL http://www.oum.ox.ac.uk/bacterialworld/
 
Description Bash the Bug 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact "Bash the bug" is a website which encourages members of the public to identify whether there is Mtb bacterial growth in a specific well of a 96 well plate containing anti-microbial drugs. These plates are being used as part of the CRyPTIC project, and the objective of this is to use multiple opinions to "call" growth or no growth in a well which is proving problematic to the experts.
Year(s) Of Engagement Activity 2017,2018
URL https://www.zooniverse.org/projects/mrniaboc/bash-the-bug
 
Description Discussing CRyPTIC on BBC world Service 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Prof Derrick Crook spoke about the CRyPTIC project and its impact on TB on News Hour on the BBC World Service

Link: https://www.bbc.co.uk/sounds/play/w172xv5c54nxwch (segment starts ~35 minutes in)
Year(s) Of Engagement Activity 2021
URL http://www.bbc.co.uk/sounds/play/w172xv5c54nxwch
 
Description Economist article about CRyPTIC 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Economist article about the CRyPTIC project and research outcomes: https://www.economist.com/science-and-technology/most-resistance-causing-mutations-in-tb-have-now-been-identified/21805727
Year(s) Of Engagement Activity 2021
URL http://www.economist.com/science-and-technology/most-resistance-causing-mutations-in-tb-have-now-bee...
 
Description Microscope on Modernising Medical Microbiology 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Join scientists as they show us how the Modernising Medical Microbiology group is using DNA to forensically track the spread of infection, detect antibiotic resistance in tuberculosis more quickly and discover the genes responsible for making bacteria dangerous.
Year(s) Of Engagement Activity 2019
 
Description New Scientist publication 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Project described in New Scientist magazine focussing on the machine learning element.
Year(s) Of Engagement Activity 2016
URL https://www.newscientist.com/article/mg23130923-000-genereading-software-to-cut-tb-diagnosis-from-mo...
 
Description Press release 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Press release for CRyPTIC project
Year(s) Of Engagement Activity 2016
 
Description Press releases for CRyPTIC project publications 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Press releases to highlight the CRyPTIC project, the manuscripts from this work that were submitted to journals, the WHO TB resistance catalogue, and a link to the CRyPTIC project data.

- Oxford University: https://www.ox.ac.uk/news/2021-10-19-largest-ever-global-study-tuberculosis-identifies-genetic-causes-drug-resistance
- EMBL-EBI: https://www.ebi.ac.uk/about/news/announcements/cryptic-cataloguing-drug-resistance-mutations-m-tuberculosis
Year(s) Of Engagement Activity 2021
URL http://www.ox.ac.uk/news/2021-10-19-largest-ever-global-study-tuberculosis-identifies-genetic-causes...
 
Description Radio Science - Live stream Q&A 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Live stream involvment in an hour long, show with Q&A about Bash The Bug and the Zooniverse project
Year(s) Of Engagement Activity 2020
 
Description Royal Society Summer Science Exhibtion 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A Stall at Summer Science Exhibition showcasing the work undertaken under CRyPTIC and encouraging participation in Bash the Bug Community project.
1,000,000 reads from Bash the Bug were acheived in 2018.
Year(s) Of Engagement Activity 2018
 
Description Science exhibition at school 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact KS2 Science exhibition for local school
Year(s) Of Engagement Activity 2019
 
Description Set up patient panels 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact We circulated an advert inviting members of the public to join patient panels to inform all aspects of the groups' work. Over 100 individuals responded, and we held two open meetings where different aspects of the work were presented. Following this smaller groups have been set up to review and advise on different projects.

Members of the public have really valued the opportunity to get involved.
Year(s) Of Engagement Activity 2014,2016
 
Description Webinar - planning and developing a zooinverse project. Bash the Bug 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Webinar explaining to audience how to set up, develop and manage a zooinverse project for citizen science projects.
Year(s) Of Engagement Activity 2020