A robust SNP barcode for typing Mycobacterium tuberculosis complex strains

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.

[1]  P. Massoure,et al.  Significance of the Identification in the Horn of Africa of an Exceptionally Deep Branching Mycobacterium tuberculosis Clade , 2012, PloS one.

[2]  Nandita Mitra,et al.  A moving target: Image guidance for stereotactic body radiation therapy for early-stage non-small cell lung cancer. , 2013, Practical radiation oncology.

[3]  JoAnne L. Flynn,et al.  Understanding Latent Tuberculosis: A Moving Target , 2010, The Journal of Immunology.

[4]  D. van Soolingen,et al.  A marked difference in pathogenesis and immune response induced by different Mycobacterium tuberculosis genotypes , 2003, Clinical and experimental immunology.

[5]  Gonçalo R. Abecasis,et al.  The Sequence Alignment/Map format and SAMtools , 2009, Bioinform..

[6]  J. Farrar,et al.  Relationship between Mycobacterium tuberculosis Genotype and the Clinical Phenotype of Pulmonary and Meningeal Tuberculosis , 2008, Journal of Clinical Microbiology.

[7]  Cole Trapnell,et al.  Ultrafast and memory-efficient alignment of short DNA sequences to the human genome , 2009, Genome Biology.

[8]  Nigel J. Martin,et al.  SpolPred: rapid and accurate prediction of Mycobacterium tuberculosis spoligotypes from short genomic sequences , 2012, Bioinform..

[9]  Marc Lipsitch,et al.  Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug resistant tuberculosis , 2013, Nature Genetics.

[10]  Michael C. Rusch,et al.  CREST maps somatic structural variation in cancer genomes with base-pair resolution , 2011, Nature Methods.

[11]  P. Small,et al.  Strain classification of Mycobacterium tuberculosis: congruence between large sequence polymorphisms and spoligotypes. , 2011, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[12]  J. Bates,et al.  World Health Organization studies on bacteriophage typing of mycobacteria. Subdivision of the species Mycobacterium tuberculosis. , 1975, The American review of respiratory disease.

[13]  M A Karachunskiĭ,et al.  [Molecular epidemiology of tuberculosis]. , 2007, Problemy tuberkuleza i boleznei legkikh.

[14]  T. Clark,et al.  PolyTB: A genomic variation map for Mycobacterium tuberculosis , 2014, Tuberculosis.

[15]  Stefan Niemann,et al.  Variable host-pathogen compatibility in Mycobacterium tuberculosis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[16]  S. Gordon,et al.  Mycobacterial Lineages Causing Pulmonary and Extrapulmonary Tuberculosis, Ethiopia , 2013, Emerging infectious diseases.

[17]  J. Farrar,et al.  The Influence of Host and Bacterial Genotype on the Development of Disseminated Disease with Mycobacterium tuberculosis , 2008, PLoS pathogens.

[18]  S. Niemann,et al.  Clade-Specific Virulence Patterns of Mycobacterium tuberculosis Complex Strains in Human Primary Macrophages and Aerogenically Infected Mice , 2013, mBio.

[19]  David G. Knowles,et al.  Fast Computation and Applications of Genome Mappability , 2012, PloS one.

[20]  Ibnelwaleed A. Hussein,et al.  Influence of Mw of LDPE and vinyl acetate content of EVA on the rheology of polymer modified asphalt , 2005 .

[21]  E. Birney,et al.  Velvet: algorithms for de novo short read assembly using de Bruijn graphs. , 2008, Genome research.

[22]  Guislaine Refregier,et al.  Resolving lineage assignation on Mycobacterium tuberculosis clinical isolates classified by spoligotyping with a new high-throughput 3R SNPs based method. , 2010, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[23]  Stefan Niemann,et al.  Phylogenetic polymorphisms in antibiotic resistance genes of the Mycobacterium tuberculosis complex. , 2014, The Journal of antimicrobial chemotherapy.

[24]  P. Hopewell,et al.  Differences among sublineages of the East-Asian lineage of Mycobacterium tuberculosis in genotypic clustering. , 2010, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[25]  Stefan Niemann,et al.  MIRU-VNTRplus: a web tool for polyphasic genotyping of Mycobacterium tuberculosis complex bacteria , 2010, Nucleic Acids Res..

[26]  Jonathan Crabtree,et al.  Global Phylogeny of Mycobacterium tuberculosis Based on Single Nucleotide Polymorphism (SNP) Analysis: Insights into Tuberculosis Evolution, Phylogenetic Accuracy of Other DNA Fingerprinting Systems, and Recommendations for a Minimal Standard SNP Set , 2006, Journal of bacteriology.

[27]  Dongfang Li,et al.  Genome sequencing of 161 Mycobacterium tuberculosis isolates from China identifies genes and intergenic regions associated with drug resistance , 2013, Nature Genetics.

[28]  Lukas Fenner,et al.  Two New Rapid SNP-Typing Methods for Classifying Mycobacterium tuberculosis Complex into the Main Phylogenetic Lineages , 2012, PloS one.

[29]  F. Emmrich,et al.  Molecular epidemiology and transmission dynamics of Mycobacterium tuberculosis in Northwest Ethiopia: new phylogenetic lineages found in Northwest Ethiopia , 2013, BMC Infectious Diseases.

[30]  J. Bates,et al.  Geographic distribution of bacteriophage types of Mycobacterium tuberculosis. , 1969, The American review of respiratory disease.

[31]  M. DePristo,et al.  The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. , 2010, Genome research.

[32]  J. Rougemont,et al.  A rapid bootstrap algorithm for the RAxML Web servers. , 2008, Systematic biology.

[33]  Stefan Niemann,et al.  Genotyping of Genetically Monomorphic Bacteria: DNA Sequencing in Mycobacterium tuberculosis Highlights the Limitations of Current Methodologies , 2009, PloS one.

[34]  S. Niemann,et al.  High Resolution Discrimination of Clinical Mycobacterium tuberculosis Complex Strains Based on Single Nucleotide Polymorphisms , 2012, PLoS ONE.

[35]  John L. Johnson,et al.  Influence of M. tuberculosis Lineage Variability within a Clinical Trial for Pulmonary Tuberculosis , 2010, PloS one.

[36]  Nick Lipley,et al.  Moving target? , 2004, Emergency nurse : the journal of the RCN Accident and Emergency Nursing Association.

[37]  Jukka Corander,et al.  Evolution and transmission of drug resistant tuberculosis in a Russian population , 2014, Nature Genetics.

[38]  I. Ial,et al.  Nature Communications , 2010, Nature Cell Biology.