Metagenomic sequencing of Mycobacteria in sputum samples.
Research type
Research Study
Full title
Rapid metagenomic sequencing based characterisation of Mycobacterium species in sputum and positive culture samples.
IRAS ID
255463
Contact name
Justin O'Grady
Contact email
Sponsor organisation
Norfolk and Norwich University Hospital (NNUH)
Clinicaltrials.gov Identifier
AF/EW, Norfolk and Norwich University Hospital Research Capability Funding (RCF) for 2018/19
Duration of Study in the UK
0 years, 5 months, 31 days
Research summary
Title: Rapid metagenomic sequencing based characterisation of Mycobacterium species in sputum and positive culture samples.
Background: Whole genome sequencing has been increasingly applied to the medical diagnostics field. In particular, it is currently being implemented in the Public Health England (PHE) for the diagnosis of tuberculosis from positive liquid cultures. This approach saves considerable time in identifying drug-resistant Mycobacteria, however, diagnosis still takes several weeks. Polymerase chain reaction (PCR) tests, like the Xpert MTB/RIF assay, provide results within hours but only testing for the Mycobacterium tuberculosis complex (not non-tuberculous mycobacteria) and rifampicin resistance. What is required is a rapid and comprehensive test capable of rapidly (within 6 hours) characterising all Mycobacteria and resistance mutations in respiratory samples. Diagnostic sequencing directly from patient samples (metagenomics) will give us information considering the Mycobacteria species and antibiotic resistance mutations.
Aims: -Establish a rapid (within 6 hours), and accessible (using MinION) method for sequencing Mycobacterium species in positive liquid cultures, removing the need to send samples to PHE for analysis, -develop a rapid, metagenomics based, diagnostic test designed to identify Mycobacteria and antibiotic resistance direct from sputum samples within 6 hours using MinION sequencing.
Methods: Implementation of Dr O’Grady's lab MinION metagenomics sequencing and analysis pipeline for the diagnosis of Mycobacteria in positive liquid and sputum samples. Mycobacterium bovis (BCG strain) will be used to find the limit-of-detection and patient’s Acid-Fast Bacillus positive sputum to determine the specificity and sensitivity of the developed method.
Benefits: Direct positive impact to the patient’s management, providing the appropriate treatment in a much shorter time-frame than any current method. This is extremely important in cases of multidrug/extensively drug-resistant tuberculosis (M/XDR-TB) in reducing the spread of the disease.
Funding: by Research Capability Funding (RCF) 2018-19.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
19/EE/0289
Date of REC Opinion
6 Jan 2020
REC opinion
Further Information Favourable Opinion