A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

Francesc Coll (), Ruth McNerney, José Afonso Guerra-Assunção, Judith R. Glynn, João Perdigão, Miguel Viveiros, Isabel Portugal, Arnab Pain, Nigel Martin and Taane G. Clark
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Francesc Coll: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine
Ruth McNerney: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine
José Afonso Guerra-Assunção: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine
Judith R. Glynn: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine
João Perdigão: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa
Miguel Viveiros: Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa
Isabel Portugal: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa
Arnab Pain: King Abdullah University of Science and Technology
Nigel Martin: School of Computer Science and Information Systems, Birkbeck College
Taane G. Clark: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine

Nature Communications, 2014, vol. 5, issue 1, 1-5

Abstract: Abstract Strain-specific genomic diversity in the Mycobacterium tuberculosis complex (MTBC) is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Several systems have been proposed to classify MTBC strains into distinct lineages and families. Here, we investigate single-nucleotide polymorphisms (SNPs) as robust (stable) markers of genetic variation for phylogenetic analysis. We identify ~92k SNP across a global collection of 1,601 genomes. The SNP-based phylogeny is consistent with the gold-standard regions of difference (RD) classification system. Of the ~7k strain-specific SNPs identified, 62 markers are proposed to discriminate known circulating strains. This SNP-based barcode is the first to cover all main lineages, and classifies a greater number of sublineages than current alternatives. It may be used to classify clinical isolates to evaluate tools to control the disease, including therapeutics and vaccines whose effectiveness may vary by strain type.

Date: 2014
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DOI: 10.1038/ncomms5812

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