title: A robust SNP barcode for typing Mycobacterium tuberculosis complex strains.
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 ~92 k 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 ~7 k 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.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Francesc
authors.initials: F
authors.lastname: Coll
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: José Afonso
authors.initials: JA
authors.lastname: Guerra-Assunção
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Glynn
authors.affiliation: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, 1649-003 Lisboa, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Perdigão
authors.affiliation: Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, 1349-008 Lisboa, Portugal.
authors.forename: Miguel
authors.initials: M
authors.lastname: Viveiros
authors.affiliation: Centro de Patogénese Molecular, Faculdade de Farmácia da Universidade de Lisboa, 1649-003 Lisboa, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Portugal
authors.affiliation: Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology, Thuwal 23955-6900, Kingdom of Saudi Arabia.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: School of Computer Science and Information Systems, Birkbeck College, London WC1E 7HX, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Martin
authors.affiliation: 1] Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK [2] Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
mesh_terms: D058893:DNA Barcoding, Taxonomic / Q000379:methods*; D030541:Databases, Genetic; D016680:Genome, Bacterial; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics*; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide