Evidence map›Paper›PMID 23496945›Full record

ArticleBMC genomics2013

The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection.

Mark N Ragheb, Christopher B Ford, Michael R Chase, Philana Ling Lin, Joanne L Flynn, Sarah M Fortune

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Armed conflict and population displacement as drivers of the evolution and dispersal of Mycobacterium tuberculosis.Proceedings of the National Academy of Sciences of the United States of America · 2016
    Article
  7. Article
  8. A multi-scale approach to designing therapeutics for tuberculosis.Integrative biology : quantitative biosciences from nano to macro · 2015
    Article
  9. Article
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Mark N RaghebDepartment of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
Christopher B Ford
Michael R Chase
Philana Ling Lin
Joanne L Flynn
Sarah M Fortune
Harvard University · USRagon Institute of MGH, MIT and Harvard · USUniversity of Pittsburgh · USUniversity of Pittsburgh Medical Center · US

Funding

Real-time surveillance to support dynamic and predictive models of MDR/XDR TBU19AI076217 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI FARMER, PAUL EDWARD · 2007 to 2011
$13.5M
Latent and Reactivation TuberculosisR01HL075845 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FLYNN, JOANNE L. · 2003 to 2007
$3.3M
Defining how the spectrum of latency affects reactivation of TBR01HL106804 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FLYNN, JOANNE L., KIRSCHNER, DENISE E · 2010 to 2013
$2.6M
Variation in M. tuberculosis in response to host selectionDP2OD001378 · OD · HARVARD SCHOOL OF PUBLIC HEALTH · PI FORTUNE, SARAH · 2007 to 2009
$2.5M
IMMUNOLOGY AND INFECTIOUS DISEASES IN PUBLIC HEALTHT32AI007638 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI RUBIN, ERIC J. · 2000 to 2014
$2.2M
NCCDPHP CDC HHS DP2 0D001378NHLBI NIH HHS R01 HL075845NHLBI NIH HHS R01 HL106804NIAID NIH HHS HHSN266200400001CNIAID NIH HHS T32 AI007638NIAID NIH HHS U19 AI076217
6 · The paper itself

Abstract

backgroundMycobacterial interspersed repetitive units (MIRUs) are minisatellites within the Mycobacterium tuberculosis (Mtb) genome. Copy number variation (CNV) in MIRU loci is used for epidemiological typing, making the rate of variation important for tracking the transmission of Mtb strains. In this study, we developed and assessed a whole-genome sequencing (WGS) approach to detect MIRU CNV in Mtb. We applied this methodology to a panel of Mtb strains isolated from the macaque model of tuberculosis (TB), the animal model that best mimics human disease. From these data, we have estimated the rate of MIRU variation in the host environment, providing a benchmark rate for future epidemiologic work.

resultsWe assessed variation at the 24 MIRU loci used for typing in a set of Mtb strains isolated from infected cynomolgus macaques. We previously performed WGS of these strains and here have applied both read depth (RD) and paired-end mapping (PEM) metrics to identify putative copy number variants. To assess the relative power of these approaches, all MIRU loci were resequenced using Sanger sequencing. We detected two insertion/deletion events both of which could be identified as candidates by PEM criteria. With these data, we estimate a MIRU mutation rate of 2.70 × 10-03 (95% CI: 3.30 × 10-04- 9.80 × 10-03) per locus, per year.

conclusionOur results represent the first experimental estimate of the MIRU mutation rate in Mtb. This rate is comparable to the highest previous estimates gathered from epidemiologic data and meta-analyses. Our findings allow for a more rigorous interpretation of data gathered from MIRU typing.

Indexed as

DNA Copy Number VariationsMutation RateAnimalsBacterial Typing TechniquesDNA, BacterialMacaca fascicularisMinisatellite RepeatsMycobacterium tuberculosisTuberculosisDNA, Bacterial

Identifiers

PMID23496945
PMCPMC3635867
OpenAlexW2151722133

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.