Evidence map›Paper›PMID 30107785›Full record

ArticleBMC genomics2018

Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data.

Benjamin Sobkowiak, Judith R Glynn, Rein M G J Houben, Kim Mallard, Jody E Phelan, José Afonso Guerra-Assunção, Louis Banda, Themba Mzembe, Miguel Viveiros, Ruth McNerney and 3 more

Open access · goldAbstract read
In one paragraph

Article in BMC genomics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 3% 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

58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  14. Within-host population dynamics of extensively drug-resistantEvolution, medicine, and public health · 2025
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  17. TGV: suite of tools to visualize transmission graphs.NAR genomics and bioinformatics · 2024
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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

13 authors at 5 institutions in 3 countries.

Benjamin SobkowiakFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. ben.sobkowiak@lshtm.ac.uk.ORCID http://orcid.org/0000-0002-1382-1137
Judith R GlynnFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Rein M G J HoubenFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Kim MallardFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Jody E PhelanFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
José Afonso Guerra-AssunçãoFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Louis BandaKaronga Prevention Study, Chilumba, Malawi.
Themba MzembeKaronga Prevention Study, Chilumba, Malawi.
Miguel ViveirosGlobal Health and Tropical Medicine, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal.
Ruth McNerneyFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Julian ParkhillWellcome Trust Sanger Institute, Hinxton, UK.
Amelia C CrampinFaculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, UK.
Taane G ClarkFaculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
London School of Hygiene & Tropical Medicine · GBMalawi Epidemiology and Intervention Research Unit · MWUniversidade Nova de Lisboa · PTUniversity of London · GBWellcome Sanger Institute · GB

Funding

Medical Research Council MC_PC_15103Medical Research Council MR/K000551/1Medical Research Council MR/M01360X/1Medical Research Council MR/N010469/1Wellcome Trust 098051
6 · The paper itself

Abstract

backgroundMixed, polyclonal Mycobacterium tuberculosis infection occurs in natural populations. Developing an effective method for detecting such cases is important in measuring the success of treatment and reconstruction of transmission between patients. Using whole genome sequence (WGS) data, we assess two methods for detecting mixed infection: (i) a combination of the number of heterozygous sites and the proportion of heterozygous sites to total SNPs, and (ii) Bayesian model-based clustering of allele frequencies from sequencing reads at heterozygous sites.

resultsIn silico and in vitro artificially mixed and known pure M. tuberculosis samples were analysed to determine the specificity and sensitivity of each method. We found that both approaches were effective in distinguishing between pure strains and mixed infection where there was relatively high (> 10%) proportion of a minor strain in the mixture. A large dataset of clinical isolates (n = 1963) from the Karonga Prevention Study in Northern Malawi was tested to examine correlations with patient characteristics and outcomes with mixed infection. The frequency of mixed infection in the population was found to be around 10%, with an association with year of diagnosis, but no association with age, sex, HIV status or previous tuberculosis.

conclusionsMixed Mycobacterium tuberculosis infection was identified in silico using whole genome sequence data. The methods presented here can be applied to population-wide analyses of tuberculosis to estimate the frequency of mixed infection, and to identify individual cases of mixed infections. These cases are important when considering the evolution and transmission of the disease, and in patient treatment.

Indexed as

AdolescentAdultBayes TheoremDNA, BacterialFemaleGenome, BacterialHumansMaleMiddle AgedMycobacterium tuberculosisPolymorphism, Single NucleotideSequence Analysis, DNATuberculosisWhole Genome SequencingYoung AdultDNA, BacterialBioinformaticsEpidemiologyGenomic analysisMixed infectionMycobacterium tuberculosisTuberculosis

Identifiers

PMID30107785
PMCPMC6092779
OpenAlexW2887960483

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.