Evidence map›Paper›PMID 26001086›Full record

ArticlePLoS computational biology2015

Metabolic Needs and Capabilities of Toxoplasma gondii through Combined Computational and Experimental Analysis.

Stepan Tymoshenko, Rebecca D Oppenheim, Rasmus Agren, Jens Nielsen, Dominique Soldati-Favre, Vassily Hatzimanikatis

Open access · goldAbstract read
In one paragraph

Article in PLoS computational biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
8.4field-weighted citation impact, top 1% 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

60 citing papers in PubMed, 106 citations in OpenAlex.

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  11. The mitochondrion ofProceedings of the National Academy of Sciences of the United States of America · 2023
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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

6 authors at 3 institutions in 2 countries.

Stepan TymoshenkoLaboratory of Computational Systems Biotechnology, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne, Switzerland; Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CMU, Geneva, Switzerland; Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Genopode, Lausanne, Switzerland.
Rebecca D OppenheimDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CMU, Geneva, Switzerland.
Rasmus AgrenDepartment of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Jens NielsenDepartment of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden.
Dominique Soldati-FavreDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CMU, Geneva, Switzerland.
Vassily HatzimanikatisDepartment of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, CMU, Geneva, Switzerland; Swiss Institute of Bioinformatics, Quartier Sorge, Batiment Genopode, Lausanne, Switzerland.
University of Geneva · CHChalmers University of Technology · SESIB Swiss Institute of Bioinformatics · CH

Funding

Howard Hughes Medical Institute
6 · The paper itself

Abstract

Toxoplasma gondii is a human pathogen prevalent worldwide that poses a challenging and unmet need for novel treatment of toxoplasmosis. Using a semi-automated reconstruction algorithm, we reconstructed a genome-scale metabolic model, ToxoNet1. The reconstruction process and flux-balance analysis of the model offer a systematic overview of the metabolic capabilities of this parasite. Using ToxoNet1 we have identified significant gaps in the current knowledge of Toxoplasma metabolic pathways and have clarified its minimal nutritional requirements for replication. By probing the model via metabolic tasks, we have further defined sets of alternative precursors necessary for parasite growth. Within a human host cell environment, ToxoNet1 predicts a minimal set of 53 enzyme-coding genes and 76 reactions to be essential for parasite replication. Double-gene-essentiality analysis identified 20 pairs of genes for which simultaneous deletion is deleterious. To validate several predictions of ToxoNet1 we have performed experimental analyses of cytosolic acetyl-CoA biosynthesis. ATP-citrate lyase and acetyl-CoA synthase were localised and their corresponding genes disrupted, establishing that each of these enzymes is dispensable for the growth of T. gondii, however together they make a synthetic lethal pair.

Indexed as

Genes, ProtozoanAcetyl Coenzyme AAlgorithmsAutomationCloning, MolecularComputational BiologyComputer SimulationDNAGene DeletionGenomeHost-Parasite InteractionsHumansMetabolic Networks and PathwaysOpen Reading FramesPhenotypeProtozoan ProteinsAcetyl Coenzyme ADNAProtozoan Proteins

Identifiers

PMID26001086
PMCPMC4441489
OpenAlexW1889799197

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.