Evidence map›Paper›PMID 30914757›Full record

ArticleScientific reports2019

An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome.

Paula J Gomez-Gonzalez, Nuria Andreu, Jody E Phelan, Paola Florez de Sessions, Judith R Glynn, Amelia C Crampin, Susana Campino, Philip D Butcher, Martin L Hibberd, Taane G Clark

Abstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

23 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. The role of cytochrome bcNature communications · 2025
    Article
  4. Article
  5. Th9 cells provide protective TB immunity.Frontiers in immunology · 2025
    Article
  6. Article
  7. Article
  8. Heliyon · 2023
    Article
  9. Functional genetic variation inFrontiers in microbiology · 2023
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. DNA Methyltransferase HsdM Induce Drug Resistance onAntibiotics (Basel, Switzerland) · 2021
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Genetic Diversity inAnnual review of genetics · 2020
    Review
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

10 authors.

Paula J Gomez-GonzalezFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Nuria AndreuFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.ORCID 0000-0001-5768-6566
Jody E PhelanFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.ORCID 0000-0001-8323-7019
Paola Florez de SessionsGenome Institute of Singapore, Biopolis, Singapore.
Judith R GlynnFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.ORCID 0000-0001-9325-4576
Amelia C CrampinFaculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Susana CampinoFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Philip D ButcherInstitute for Infection & Immunity, St George's University of London, London, United Kingdom.
Martin L HibberdFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.
Taane G ClarkFaculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. taane.clark@lshtm.ac.uk.ORCID 0000-0001-8985-9265

Funding

Biotechnology and Biological Sciences Research Council BB/R013063/1Medical Research Council MR/M01360X/1Medical Research Council MR/N010469/1Medical Research Council MR/R020973/1Medical Research Council MR/R025576/1
6 · The paper itself

Abstract

Human tuberculosis disease (TB), caused by Mycobacterium tuberculosis (Mtb), is a complex disease, with a spectrum of outcomes. Genomic, transcriptomic and methylation studies have revealed differences between Mtb lineages, likely to impact on transmission, virulence and drug resistance. However, so far no studies have integrated sequence-based genomic, transcriptomic and methylation characterisation across a common set of samples, which is critical to understand how DNA sequence and methylation affect RNA expression and, ultimately, Mtb pathogenesis. Here we perform such an integrated analysis across 22 M. tuberculosis clinical isolates, representing ancient (lineage 1) and modern (lineages 2 and 4) strains. The results confirm the presence of lineage-specific differential gene expression, linked to specific SNP-based expression quantitative trait loci: with 10 eQTLs involving SNPs in promoter regions or transcriptional start sites; and 12 involving potential functional impairment of transcriptional regulators. Methylation status was also found to have a role in transcription, with evidence of differential expression in 50 genes across lineage 4 samples. Lack of methylation was associated with three novel variants in mamA, likely to cause loss of function of this enzyme. Overall, our work shows the relationship of DNA sequence and methylation to RNA expression, and differences between ancient and modern lineages. Further studies are needed to verify the functional consequences of the identified mechanisms of gene expression regulation.

Indexed as

DNA, BacterialDNA MethylationGene Expression RegulationMycobacterium tuberculosisPolymorphism, Single NucleotideTranscriptomeTuberculosisGenome-Wide Association StudyHumansPromoter Regions, GeneticDNA, Bacterial

Identifiers

PMID30914757
PMCPMC6435705

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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.