Evidence map›Paper›PMID 25315994›Full record

ArticleBMC systems biology2014

A curated C. difficile strain 630 metabolic network: prediction of essential targets and inhibitors.

Mathieu Larocque, Thierry Chénard, Rafael Najmanovich

Open access · diamondAbstract readValidation Study
In one paragraph

Article in BMC systems biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 40 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Vegetative Cell and Spore Proteomes ofJournal of proteome research · 2019
    Article
  8. Review
  9. Network-Based Metabolism-Centered Screening of Potential Drug Targets inFrontiers in cellular and infection microbiology · 2019
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. FEBS open bio · 2017
    Article
  20. 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

3 authors at 1 institution in 1 country.

Mathieu LarocqueDepartment of Biochemistry, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada. mathieu.larocque2@usherbrooke.ca.
Thierry ChénardDepartment of Biochemistry, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada. thierry.chenard@usherbrooke.ca.
Rafael NajmanovichDepartment of Biochemistry, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC, J1H 5N4, Canada. rafael.najmanovich@usherbrooke.ca.
Université de Sherbrooke · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundClostridium difficile is the leading cause of hospital-borne infections occurring when the natural intestinal flora is depleted following antibiotic treatment. Current treatments for Clostridium difficile infections present high relapse rates and new hyper-virulent and multi-resistant strains are emerging, making the study of this nosocomial pathogen necessary to find novel therapeutic targets.

resultsWe present iMLTC806cdf, an extensively curated reconstructed metabolic network for the C. difficile pathogenic strain 630. iMLTC806cdf contains 806 genes, 703 metabolites and 769 metabolic, 117 exchange and 145 transport reactions. iMLTC806cdf is the most complete and accurate metabolic reconstruction of a gram-positive anaerobic bacteria to date. We validate the model with simulated growth assays in different media and carbon sources and use it to predict essential genes. We obtain 89.2% accuracy in the prediction of gene essentiality when compared to experimental data for B. subtilis homologs (the closest organism for which such data exists). We predict the existence of 76 essential genes and 39 essential gene pairs, a number of which are unique to C. difficile and have non-existing or predicted non-essential human homologs. For 29 of these potential therapeutic targets, we find 125 inhibitors of homologous proteins including approved drugs with the potential for drug repositioning, that when validated experimentally could serve as starting points in the development of new antibiotics.

conclusionsWe created a highly curated metabolic network model of C. difficile strain 630 and used it to predict essential genes as potential new therapeutic targets in the fight against Clostridium difficile infections.

Indexed as

Models, BiologicalClostridioides difficileComputational BiologyEnterocolitis, PseudomembranousGenes, EssentialHumansMetabolic Networks and PathwaysSystems Biology

Identifiers

PMID25315994
PMCPMC4207893
OpenAlexW2159184004

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.