Evidence map›Paper›PMID 32264819›Full record

ArticleBMC microbiology2020

Gene expression responses to anti-tuberculous drugs in a whole blood model.

Philip Kam Weng Kwan, Wenwei Lin, Ahmad Nazri Mohamed Naim, Balamurugan Periaswamy, Paola Florez De Sessions, Martin L Hibberd, Nicholas I Paton

Open access · goldAbstract read
In one paragraph

Article in BMC microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.1field-weighted citation impact, top 46% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. 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

7 authors at 5 institutions in 2 countries.

Philip Kam Weng KwanDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore.
Wenwei LinDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore.
Ahmad Nazri Mohamed NaimGenome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Balamurugan PeriaswamyGenome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Paola Florez De SessionsGenome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Martin L HibberdGenome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore.
Nicholas I PatonDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore. nick_paton@nuhs.edu.sg.
Genome Institute of Singapore · SGAgency for Science, Technology and Research · SGLondon School of Hygiene & Tropical Medicine · GBNational University Health System · SGNational University of Singapore · SG

Funding

National Medical Research Council NMRC/CSA/0050/2013National Medical Research Council NMRC/TCR/011-NUHS/2014
6 · The paper itself

Abstract

backgroundThere is a need for better tools to evaluate new or repurposed TB drugs. The whole blood bactericidal activity (WBA) assay has been advocated for this purpose. We investigated whether transcriptional responses in the WBA assay resemble TB responses in vivo, and whether the approach might additionally reveal mechanisms of action.

results1422 of 1798 (79%) of differentially expressed genes in WBA incubated with the standard combination of rifampicin, isoniazid, pyrazinamide and ethambutol were also expressed in sputum (P < 0.0001) obtained from patients taking the same combination of drugs; these comprised well-established treatment-response genes. Gene expression profiles in WBA incubated with the standard drugs individually, or with moxifloxacin or faropenem (with amoxicillin and clavulanic acid) clustered by individual drug exposure. Distinct pathways were detected for individual drugs, although only with isoniazid did these relate to known mechanisms of drug action.

conclusionsSubstantial agreement between whole blood cultures and sputum and the ability to differentiate individual drugs suggest that transcriptomics may add value to the whole blood assay for evaluating new TB drugs.

Indexed as

Antitubercular AgentsBacterial ProteinsBloodDrug CombinationsDrug RepositioningEthambutolGene Expression ProfilingGene Expression Regulation, BacterialHumansIsoniazidModels, BiologicalMycobacterium tuberculosisOligonucleotide Array Sequence AnalysisPyrazinamideRifampinSputumAntitubercular AgentsBacterial ProteinsDrug CombinationsEthambutolIsoniazidPyrazinamideRifampinAnti-tuberculosis drugsFaropenemGene expressionMechanism of actionMicroarrayTranscriptomeTuberculosisWhole blood assay

Identifiers

PMID32264819
PMCPMC7140558
OpenAlexW3014675264

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.