Evidence map›Paper›PMID 31109296›Full record

ArticleBMC genomics2019

Whole genome sequencing Mycobacterium tuberculosis directly from sputum identifies more genetic diversity than sequencing from culture.

Camus Nimmo, Liam P Shaw, Ronan Doyle, Rachel Williams, Kayleen Brien, Carrie Burgess, Judith Breuer, Francois Balloux, Alexander S Pym

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in BMC genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed, 1 pooled it
8.9field-weighted citation impact, top 2% 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

61 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Microbial genomics · 2025
    Pooled it
  2. Review
  3. What is new in tuberculosis?Clinical medicine (London, England) · 2026
    Review
  4. Article
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  11. Optimizing culture-free approaches to recover high qualitymedRxiv : the preprint server for health sciences · 2025
    Article
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  15. Article
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  18. Article
  19. Article
  20. Enhancing diagnostic efficiency of pyrazinamide resistance inCurrent research in microbial sciences · 2025
    Article

1 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 2 countries.

Camus NimmoDivision of Infection and Immunity, University College London, London, WC1E 6BT, UK. c.nimmo.04@cantab.net.ORCID http://orcid.org/0000-0001-7355-4651
Liam P ShawUCL Genetics Institute, University College London, London, WC1E 6BT, UK.
Ronan DoyleDivision of Infection and Immunity, University College London, London, WC1E 6BT, UK.
Rachel WilliamsDivision of Infection and Immunity, University College London, London, WC1E 6BT, UK.
Kayleen BrienAfrica Health Research Institute, Durban, South Africa.
Carrie BurgessDivision of Infection and Immunity, University College London, London, WC1E 6BT, UK.
Judith BreuerDivision of Infection and Immunity, University College London, London, WC1E 6BT, UK.
Francois BallouxUCL Genetics Institute, University College London, London, WC1E 6BT, UK.
Alexander S PymAfrica Health Research Institute, Durban, South Africa.
University College London · GBAfrica Health Research Institute · ZAUniversity of London · GBUniversity of Oxford · GB

Funding

Medical Research Council MR/P007597/1National Institute for Health Research BRC/176/III/JB/101350Seventh Framework Programme 304875Wellcome Trust 203583/Z/16/Z
6 · The paper itself

Abstract

backgroundRepeated culture reduces within-sample Mycobacterium tuberculosis genetic diversity due to selection of clones suited to growth in culture and/or random loss of lineages, but it is not known to what extent omitting the culture step altogether alters genetic diversity. We compared M. tuberculosis whole genome sequences generated from 33 paired clinical samples using two methods. In one method DNA was extracted directly from sputum then enriched with custom-designed SureSelect (Agilent) oligonucleotide baits and in the other it was extracted from mycobacterial growth indicator tube (MGIT) culture.

resultsDNA directly sequenced from sputum showed significantly more within-sample diversity than that from MGIT culture (median 5.0 vs 4.5 heterozygous alleles per sample, p = 0.04). Resistance associated variants present as HAs occurred in four patients, and in two cases may provide a genotypic explanation for phenotypic resistance.

conclusionsCulture-free M. tuberculosis whole genome sequencing detects more within-sample diversity than a leading culture-based method and may allow detection of mycobacteria that are not actively replicating.

Indexed as

Genetic VariationAdultDrug Resistance, BacterialHumansMycobacterium tuberculosisSputumTuberculosisWhole Genome SequencingDrug-resistant tuberculosisHeteroresistanceMycobacterium tuberculosisSputumWhole genome sequencingWithin-patient diversity

Identifiers

PMID31109296
PMCPMC6528373
OpenAlexW2949601837

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.