INTEGRATING GENOMICS, EPIDEMIOLOGY AND EVOLUTION TO ACCELERATE TUBERCULOSIS ERADICATION

Grant agreement ID: 638553
Project period: 1 July 2015 – 30 June 2020
Funding: 1,671,875 €

The project

TB-ACCELERATE IS an ERC project at IBV-CSIC and FISABIO with PI Iñaki Comas.

This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement ID 638553.

Objective

When the scale of the tuberculosis (TB) epidemic was highlighted by its declaration as a “Global Emergency” by WHO in 1993, it was envisaged that the efficient use of existing tools would result in a progressive decline towards eradication. This has not occurred. At the current pace of decline in TB incidence the Millennium objective to eradicate it by 2050 will not be met. Predictions of epidemiological models were inaccurate and current control programs and technologies have shown their limitations to control the transmission of the disease. To overcome these limitations we need a technological, methodological and conceptual leap forward that can reveal the unknowns of TB epidemiology. I propose whole genome sequencing (WGS) as the technology that can mediate this advance. While WGS has been applied mostly to retrospective datasets I propose to use it in prospective samples from a low-burden region at a population scale. Genome information will fill the gap between epidemiology and evolution to have a direct impact on public health. This will allow to develop innovative methodologies to describe transmission at an unprecedented resolution and as a consequence to differentiate among risks factors associated to the bacteria, the host, the environment and their interactions. Elucidation of these factors will lead to better models used to design new strategies and accelerate global TB eradication. In addition, I will show how the real-time integration of data in public eHealth systems combined with in situ interventions will accelerate TB eradication. The strength of the project resides in its multidisciplinary approach to TB epidemiology that will provide answers to yet-out-of-reach questions. It will lead to improving health status at the local level as well as to epidemiological and control programs at a global scale. In summary, the project will open new ways to foster the long sought outcome of the tuberculosis community: TB eradication.

Published results

  • Goig GA, Cancino-Muñoz I, Torres-Puente M, Villamayor LM, Navarro D, Borrás R, Comas I. Whole-genome sequencing of Mycobacterium tuberculosis directly from clinical samples for high-resolution genomic epidemiology and drug resistance surveillance: an observational study. The Lancet Microbe. 2020 August 01; 1 (4): E175-E183. https://doi.org/10.1016/S2666-5247(20)30060-4
  • Goig GA, Blanco S, García-Basteiro AL, Comas I. Contaminant DNA in bacterial sequencing experiments is a major source of false genetic variability. BMC Biol. 2020 March 02; 18: 24. https://doi.org/10.1186/s12915-020-0748-z
  • López MG, Dogba JB , Torres-Puente M, Goig GA, Moreno-Molina M, Villamayor LM, Cadmus S, Comas I. Tuberculosis in Liberia: high multidrug-resistance burden, transmission and diversity modelled by multiple importation events. Microb Genom. 2020 Jan 14; DOI: 10.1099/mgen.0.000325
  • Xu Y, Cancino-Muñoz I, Torres-Puente M, Villamayor LM, Borrás R, Borrás-Máñez M, Bosque M, Camarena JJ, Colomer-Roig E, Colomina J, Escribano I, Esparcia-Rodríguez O, Gil-Brusola A, Gimeno C, Gimeno-Gascón A, Gomila-Sard B, González-Granda D, Gonzalo-Jiménez N, Guna-Serrano MR, López-Hontangas JL, Martín-González C, Moreno-Muñoz R, Navarro D, Navarro M, Orta N, Pérez E, Prat, Carlos Rodríguez J, Ruiz-García MM, Vanaclocha H, Colijn C, Comas I. High-resolution mapping of tuberculosis transmission: Whole genome sequencing and phylogenetic modelling of a cohort from Valencia Region, Spain. PLoS Med. 2019 Oct 31; 16 (10): e1002961.
  • Cancino-Muñoz I, Gil-Brusola A, Torres-Puente M, Mariner-Llicer C, Dogba J, Akinseye V, Adesokan K, Kwaghe A, Ejeh F, Cadmus S, Comas I. Development and application of affordable SNP typing approaches to genotype Mycobacterium tuberculosis complex strains in low and high burden countries. Sci Rep. 2019 Oct 25; 9: 15343.
  • Goig GA, Torres-Puente M, Mariner-Llicer C, Villamayor LM, Chiner-Oms Á, Gil-Brusola A, Borrás R, Comas I. Towards next-generation diagnostics for tuberculosis: identification of novel molecular targets by large-scale comparative genomics. Bioinformatics. 2019 Oct 3; btz729
  • Chiner-Oms Á, Berney M, Boinett C, González-Candelas F, Young DB, Gagneux S, Jacobs WR, Parkhill J, Cortes T, Comas I. Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex. Nat Comm. 2019; 10 (1): 3994.
  • Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A, Ezewudo M, Farhat MR, Guthrie JL, Laukens K, Miotto P, Ofori-Anyinam B, Dreyer V, Supply P, Suresh A, Utpatel C, van Soolingen D, Zhou Y, Ashton PM, Brites D, Cabibbe AM, de Jong BC, de Vos M, Menardo F, Gagneux S, Gao Q, Heupink TH, Liu Q, Loiseau C, Rigouts L, Rodwell TC, Tagliani E, Walker TM, Warren RM, Zhao Y, Zignol M, Schito M, Gardy J, Cirillo DM, Niemann S, Comas I, Van Rie A. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nat Rev Microb. 2019; 17: 533 – 545
  • Chiner-Oms Á, Comas I. Large genomics datasets shed light on the evolution of the Mycobacterium tuberculosis complex. Infect Genet Evol. 2019; 72:10-15.
    Chiner-Oms Á, Sánchez-Busó L., Corander J, Gagneux S, Harris S, Young D, González-Candelas F., Comas I. Genomic determinants of speciation and spread of the Mycobacterium tuberculosis complex. Sci Adv. 2019;5(6):eaaw3307
    Cancino-Muñoz I, Moreno-Molina M, Furió V, Goig GA, Torres-Puente M, Chiner-Oms Á, et al. Cryptic Resistance Mutations Associated With Misdiagnoses of Multidrug-Resistant Tuberculosis. J Infect Dis. 2019 Jun 19;220(2):316–20
    Moreno-Molina M, Comas I, Furió V. The Future of TB Resistance Diagnosis: The Essentials on Whole Genome Sequencing and Rapid Testing Methods. Arch Bronconeumol. 2019 Feb 19.
  • Chiner-Oms Á, González-Candelas F, Comas I. Gene expression models based on a reference laboratory strain are poor predictors of Mycobacterium tuberculosis complex transcriptional diversity. Sci Rep. 2018 Feb 28;8(1):3813.
  • Comas I, Gardy J. TB transmission: closing the gaps. EBioMedicine. 2018; 34:4 – 5
  • Comas I, Hailu E, Kiros T, Bekele S, Mekonnen W, Gumi B, Tschopp R, Ameni G, Hewinson RG, Robertson BD, Goig GA, Stucki D, Gagneux S, Aseffa A, Young D, Berg S. Population genomics of Mycobacterium tuberculosis in Ethiopia contradicts the virgin soil hypothesis for human tuberculosis in Sub-Saharan Africa. Curr Biol. 2015 Dec 21;25(24):3260-6.

Thesis

  • Decoding tuberculosis transmission and drug resistance in Valencia region using whole genome sequencing.
    • Author: Irving Cancino Muñoz
    • Supervision: Iñaki Comas
      Program: Doctoral Program in Biomedicine and Biotechnology (University of Valencia)
      Date: 26/10/2020
  • Applied genomics for tuberculosis diagnosis and surveillance.
    • Author: Galo Adrian Goig
    • Supervision: Iñaki Comas
    • Program: Doctoral Program in Biomedicine and Biotechnology (University of Valencia)
    • Date: 24/07/2020
  • Evolutionary systems biology of the Mycobacterium tuberculosis complex.
    • Author: Álvaro Chiner-Oms
    • Supervision: Iñaki Comas and Fernando González-Candelas
    • Program: Doctoral Program in Biomedicine and Biotechnology (University of Valencia)
    • Date: 28/06/2019