title: PolyTB: a genomic variation map for Mycobacterium tuberculosis.
abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to the ability to generate whole genome information in clinical isolates of M. tuberculosis complex (MTBC). The identification of informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb in the context of epidemiological, diagnostic and clinical studies. Mtb genomic datasets are increasingly available as raw sequences, which are potentially difficult and computer intensive to process, and compare across studies. Here we have processed the raw sequence data (>1500 isolates, eight studies) to compile a catalogue of SNPs (n = 74,039, 63% non-synonymous, 51.1% in more than one isolate, i.e. non-private), small indels (n = 4810) and larger structural variants (n = 800). We have developed the PolyTB web-based tool (http://pathogenseq.lshtm.ac.uk/polytb) to visualise the resulting variation and important meta-data (e.g. in silico inferred strain-types, location) within geographical map and phylogenetic views. This resource will allow researchers to identify polymorphisms within candidate genes of interest, as well as examine the genomic diversity and distribution of strains. PolyTB source code is freely available to researchers wishing to develop similar tools for their pathogen of interest.
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK. Electronic address: francesc.coll@lshtm.ac.uk.
authors.forename: Francesc
authors.initials: F
authors.lastname: Coll
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Preston
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK.
authors.forename: José Afonso
authors.initials: JA
authors.lastname: Guerra-Assunção
authors.affiliation: Pathogen Genomics Laboratory, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia; Sydney Emerging Infections and Biosecurity Institute and School of Public Health, Sydney, NSW 2006, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Hill-Cawthorn
authors.affiliation: Pathogen Genomics Faculty, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridge, UK.
authors.forename: David
authors.initials: D
authors.lastname: Harris
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: Centre for Immunology and Infectious Disease, Queen Mary University of London, E1 2AT London, UK.
authors.forename: Francis
authors.initials: F
authors.lastname: Drobniewski
authors.affiliation: Swiss Tropical and Public Health Institute, 4002 Basel, Switzerland.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.affiliation: Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Glynn
authors.affiliation: Pathogen Genomics Laboratory, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia.
authors.forename: Arnab
authors.initials: A
authors.lastname: Pain
authors.affiliation: Pathogen Genomics Faculty, Wellcome Trust Sanger Institute, Hinxton, CB10 1SA Cambridge, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: McNerney
authors.affiliation: School of Computer Science and Information Systems, Birkbeck College, WC1E 7HX London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Martin
authors.affiliation: Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK; Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, WC1E 7HT London, UK.
authors.forename: Taane G
authors.initials: TG
authors.lastname: Clark
mesh_terms: D002874:Chromosome Mapping; D016208:Databases, Factual; D017353:Gene Deletion; D014644:Genetic Variation / Q000235:genetics; D016680:Genome, Bacterial / Q000235:genetics*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics; D014376:Tuberculosis / Q000235:genetics*
keywords: Database; Genomics; Molecular epidemiology; Mycobacterium tuberculosis; Software; Whole-genome sequencing