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Rapid whole-genome sequencing dramatically reduces time taken to diagnose XDR Tuberculosis


Dj, 18/07/2013 - 09:49

Rapid whole-genome sequencing dramatically reduces time taken to diagnose XDR Tuberculosis



  • A retrospective study reveals the potential of rapid whole-genome sequencing to identify resistance when mutations known to confer resistance are detected. 
  • The study has been published as a Letter to the Editor in the journal The New England Journal of Medicine.

The researcher from the Centro Nacional de Análisis Genómico (CNAG) and the Centre for Genomic Regulation (CRG) Marc A. Marti-Renom has participated in a study that reveals the potential of rapid whole-genome sequencing in a hospital setting to reduce the time taken to diagnose extensively drug-resistant (XDR) tuberculosis from weeks to days. The study published as a Letter to the Editor in the prestigious journal The New England Journal of Medicine reported a finding that might guide clinicians and reference laboratories in the identification of drug resistant tuberculosis.

The study, led by researchers from the University of Cambridge and Public Health England, started when a 38-year old male patient had a first admission to a hospital with clinical and radiological features consistent with pulmonary tuberculosis. Current laboratory methods of identifying and typing Mycobacterium tuberculosis complex (causative agent of most cases of tuberculosis) were performed. In parallel, DNA was extracted from the sample and sequenced with the use of the Illumina MiSeq platform. 

The results of rapid whole-genome sequencing revealed a mixed infection caused by two distantly related Beijing strains of M. Tuberculosis that was not apparent with the standard laboratory techniques. It also identified that the second strain, which was responsible for the 30% of the bacteria present in the patient, had a mutation in a gene targeted by antibiotics. The 3D modelling of the mutated protein structure strain, performed by the CNAG and CRG researcher Marc A. Marti-Renom, helped to better understand the molecular mechanisms that underlie XDR tuberculosis.

The study suggests that rapid whole-genome sequencing complements current methods for identifying and typing M. tuberculosis complex offering the ultimate molecular resolution in a hospital setting.
Reference publication: Whole-Genome Sequencing for Rapid Susceptibility Testing of M. tuberculosis. Claudio U. Köser, Josephine M. Bryant,Jennifer Becq, M. Estée Török, Matthew J. Ellington, Marc A. Marti-Renom, Andrew J. Carmichael,  Julian Parkhill, Geoffrey P. Smith, Sharon J. Peacock. The New England Journal of Medicine (2013) doi: 10.1056/NEJMc1215305

About Marc A. Marti-Renom
Marc A. Marti-Renom is the Genome Biology Group Leader at the CNAG and has a second affiliation as Structural Genomics Group Leader at the CRG. He holds a degree in Biology and a PhD in Biophysics from the Autonomous University of Barcelona. He trained in the modelling of protein structure in the laboratory of Prof. Andrej Sali at Rockefeller University, in the USA. Later, he was appointed assistant professor at the University of California in San Francisco, also in the USA. Between 2006 and 2011, he was head of the Structural Genomics Laboratory in the Prince Felipe Research Centre in Valencia (CIPF). Marc A. Marti-Renom is associate editor of the journal PLoS Computational Biology and has co-authored over 70 articles published in prestigious scientific journals.

About the Centro Nacional de Análisis Genómico (CNAG)
The CNAG was created in 2009 with support from the Ministry of Science and Innovation and the Government of Catalonia as a platform integrated into the Barcelona Science Park. The mission of the centre is to carry out large-scale DNA analysis and sequencing projects in collaboration with researchers from Catalonia, Spain and other parts of the world and ensure the international competitiveness of our country in the strategic area of genomics.
The centre, directed by Dr. Ivo Gut, has a highly-qualified team of 55 (50% of the staff hold doctorates), and a fleet of 13 latest-generation sequencers, which have allowed it to achieve a sequencing capacity of up to 600 Gbases/day, equivalent to sequencing six human genomes per day. This makes the CNAG the second ranked European centre for sequencing capacity.

About the Centre for Genomic Regulation (CRG)
The CRG is an international institute for biomedical research excellence, created in December 2000. It is a non-profit foundation, and relies on the participation of the Government of Catalonia, via the Department of Economics and Knowledge and the Department of Health, the Pompeu Fabra University, and the Ministry of Economy and Competitiveness. Its mission is to discover and advance knowledge for the benefit of society, public health and economic prosperity.
The CRG believes that the medicine of the future depends on innovative science today. This requires an interdisciplinary team focused on understanding the complexity of life, from the genome and the cell, to the whole organism and its interaction with the environment, providing an overall view of genetic diseases.
The CRG’s main goals are to become a global reference centre in the field of biomedical sciences, to communicate and establish a bilateral dialogue with society, provide advanced training to the next generation of scientists and transform new knowledge into benefit and value to society and the economy. The combination of the 'know how' of top scientists from around the world and the availability of cutting-edge equipment, make the CRG a unique centre with high-level scientific production in an international context and the best scientific and technical services for research.

Further information:
Centre for Genomic Regulation (CRG) - Laia Cendrós · +34 93 316 02 37