Sublineage structure analysis of Mycobacterium tuberculosis complex strains using multiple-biomarker tensors

Ozcaglar, Cagri; Shabbeer, Amina; Vandenberg, Scott; Yener, Bülent; Bennett, Kristin P.

doi:10.1186/1471-2164-12-s2-s1

Cited by 17 publications

(18 citation statements)

References 38 publications

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“…Mycobacteria can be classified with increasing discrimination using large sequence and single nucleotide polymorphisms, direct repeat markers (spoligotyping) and then variable number of tandem repeat (VNTR) markers (Brudey et al, 2006, Gagneux and Small, 2007, Kato-Maeda et al, 2011, Ozcaglar et al, 2011, Supply et al, 2006. The majority of M. bovis isolates in Northern Ireland belong to a single spoligotype (SB0140) and so we used both spoligotyping and VNTR typing to define genotypes ("strains").…”

Section: Introductionmentioning

confidence: 99%

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland

Wright

Allen

Mallon

et al. 2013

Infection, Genetics and Evolution

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Strains of many infectious diseases differ in parameters that influence epidemic spread, for example virulence, transmissibility, detectability and host specificity. Knowledge of inter-strain variation can be exploited to improve management and decrease disease incidence. Bovine tuberculosis (bTB) is increasingly prevalent among farmed cattle in the UK, exerting a heavy economic burden on the farming industry and government. We aimed to determine whether strains of Mycobacterium bovis (the causative agent of bTB) identified and classified using genetic markers (spoligotyping and multi-locus VNTR analysis) varied in response to the tuberculin skin test; this being the primary method of bTB detection used in the UK. Inter-strain variation in detectability of M. bovis could have important implications for disease control. The skin test is based on a differential delayed type hypersensitivity (DTH) response to intradermal injections of purified protein derivative (PPD) from M. bovis (PPD-B) and Mycobacterium avium (PPD-A). We searched for an association between skin test response (PPD-B skin rise minus PPD-A skin rise) and M. bovis genotype at the disclosing test in culture-confirmed cases using a field dataset consisting of 21,000 isolates belonging to 63 genotypes of M. bovis from cattle in Northern Ireland. We found no substantial variation among genotypes (estimated responses clustered tightly around the mean) controlling for animal sex, breed and test effects. We also estimated the ratio of skin test detected to undetected cases (i.e. cases only detected at abattoir). The skin test detection ratio varied among abattoirs with some detecting a greater proportion of cases than others but this variation was unrelated to the community composition of genotypes within each abattoir catchment. These two lines of evidence indicate that M. bovis genotypes in Northern Ireland have similar detectability using the skin test.

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Section: Introductionmentioning

confidence: 99%

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland

Wright

Allen

Mallon

et al. 2013

Infection, Genetics and Evolution

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“…The values are estimated from the CDC data using maximum likelihood method, and values are found. Mutation length distribution is derived from this probability as follows: (4) where values are calculated from the mutation history of spoligotypes using starting point of each mutation and thereby the length of the longest block of contiguous spacers for each mutation event.…”

Section: ) Starting Point Model (Spm)mentioning

confidence: 99%

“…DNA fingerprinting of MTBC strains is used for tracking the transmission of tuberculosis. Isolates from TB patients are genotyped using multiple biomarkers, which include spacer oligonucleotide types (spoligotypes), mycobacterium interspersed repetitive units-variable number tandem repeats (MIRU-VNTR), and IS6110 restriction fragment length polymorphism (RFLP) [2]- [4].…”

mentioning

confidence: 99%

Inferred Spoligoforest Topology Unravels Spatially Bimodal Distribution of Mutations in the DR Region

Ozcaglar

Shabbeer

Kurepina³

et al. 2012

IEEE Trans.on Nanobioscience

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Biomarkers of Mycobacterium tuberculosis complex (MTBC) mutate over time. Among the biomarkers of MTBC, spacer oligonucleotide type (spoligotype) and mycobacterium interspersed repetitive unit (MIRU) patterns are commonly used to genotype clinical MTBC strains. In this study, we present an evolution model of spoligotype rearrangements using MIRU patterns to disambiguate the ancestors of spoligotypes. We use a large patient dataset from the United States Centers for Disease Control and Prevention (CDC) to generate this model. Based on the contiguous deletion assumption and rare observation of convergent evolution, we first generate the most parsimonious forest of spoligotypes, called a spoligoforest, using three genetic distance measures. An analysis of topological attributes of the spoligoforest and number of variations at the direct repeat (DR) locus of each strain reveals interesting properties of deletions in the DR region. First, we compare our mutation model to existing mutation models of spoligotypes and find that our mutation model produces as many within-lineage mutation events as other models, with slightly higher segregation accuracy. Second, based on our mutation model, the number of descendant spoligotypes follows a power law distribution. Third, contrary to prior studies, the power law distribution does not plausibly fit to the mutation length frequency. Moreover, we find that the total number of mutation events at consecutive spacers follows a spatially bimodal distribution. The two modes are spacers 13 and 40, which are hotspots for chromosomal rearrangements, and the change point is spacer 34, which is absent in most MTBC strains. Based on this observation, we built two alternative models for mutation length frequency: the Starting Point Model (SPM) and the Longest Block Model (LBM). Both models are plausibly good fits to the mutation length frequency distribution, as verified by the goodness-of-fit test. We also apply SPM and LBM to a dataset from Institut Pasteur de Guadeloupe and verify that these models hold for different strain datasets.

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“…Details of the reviewing process are presented in the BMC Genomics introduction article [15], with at least three reviews for each submission (see Additional File 1 of ref. [15] for a list of reviewers) and in the majority of the acceptable papers going through two rounds of reviews.…”

Section: Submissions and Review For Incob/iscb-asia 2011mentioning

confidence: 99%

Towards big data science in the decade ahead from ten years of InCoB and the 1st ISCB-Asia Joint Conference

et al. 2011

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The 2011 International Conference on Bioinformatics (InCoB) conference, which is the annual scientific conference of the Asia-Pacific Bioinformatics Network (APBioNet), is hosted by Kuala Lumpur, Malaysia, is co-organized with the first ISCB-Asia conference of the International Society for Computational Biology (ISCB). InCoB and the sequencing of the human genome are both celebrating their tenth anniversaries and InCoB’s goalposts for the next decade, implementing standards in bioinformatics and globally distributed computational networks, will be discussed and adopted at this conference. Of the 49 manuscripts (selected from 104 submissions) accepted to BMC Genomics and BMC Bioinformatics conference supplements, 24 are featured in this issue, covering software tools, genome/proteome analysis, systems biology (networks, pathways, bioimaging) and drug discovery and design.

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Sublineage structure analysis of Mycobacterium tuberculosis complex strains using multiple-biomarker tensors

Cited by 17 publications

References 38 publications

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland

Detectability of bovine TB using the tuberculin skin test does not vary significantly according to pathogen genotype within Northern Ireland

Inferred Spoligoforest Topology Unravels Spatially Bimodal Distribution of Mutations in the DR Region

Towards big data science in the decade ahead from ten years of InCoB and the 1st ISCB-Asia Joint Conference

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