Evidence map›Paper›PMID 31730853›Full record

ArticleCell2019

Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage.

Rebecca R Stanway, Ellen Bushell, Anush Chiappino-Pepe, Magali Roques, Theo Sanderson, Blandine Franke-Fayard, Reto Caldelari, Murielle Golomingi, Mary Nyonda, Vikash Pandey and 12 more

Abstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
–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

74 citing papers in PubMed.

  1. Article
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  10. Targeting Mitochondrial Function inInternational journal of molecular sciences · 2025
    Review
  11. Review
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  18. Revisiting theNPJ drug discovery · 2025
    Article
  19. ThemSphere · 2024
    Article
  20. Article

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

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

22 authors.

Rebecca R StanwayInstitute of Cell Biology, University of Bern, Bern 3012, Switzerland.
Ellen BushellWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK; Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden.
Anush Chiappino-PepeLaboratory of Computational Systems Biotechnology, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland.
Magali RoquesInstitute of Cell Biology, University of Bern, Bern 3012, Switzerland.
Theo SandersonWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Blandine Franke-FayardLeiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden 2333ZA, the Netherlands.
Reto CaldelariInstitute of Cell Biology, University of Bern, Bern 3012, Switzerland.
Murielle GolomingiInstitute of Cell Biology, University of Bern, Bern 3012, Switzerland.
Mary NyondaDepartment of Microbiology & Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland.
Vikash PandeyLaboratory of Computational Systems Biotechnology, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland; Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden.
Frank SchwachWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Séverine ChevalleyLeiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden 2333ZA, the Netherlands.
Jai RamesarLeiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden 2333ZA, the Netherlands.
Tom MetcalfWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Colin HerdWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.
Paul-Christian BurdaInstitute of Cell Biology, University of Bern, Bern 3012, Switzerland; Bernhard Nocht Institute for Tropical Medicine, Hamburg 20359, Germany.
Julian C RaynerWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK; Cambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge CB2, 0XY, UK.
Dominique Soldati-FavreDepartment of Microbiology & Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva 1211, Switzerland.
Chris J JanseLeiden Malaria Research Group, Parasitology, Center of Infectious Diseases, Leiden University Medical Center (LUMC), Leiden 2333ZA, the Netherlands.
Vassily HatzimanikatisLaboratory of Computational Systems Biotechnology, École Polytechnique Fédérale de Lausanne, EPFL, Lausanne 1015, Switzerland.
Oliver BillkerWellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK; Molecular Infection Medicine Sweden (MIMS), Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden. Electronic address: oliver.billker@umu.se.
Volker T HeusslerInstitute of Cell Biology, University of Bern, Bern 3012, Switzerland. Electronic address: volker.heussler@izb.unibe.ch.

Funding

Medical Research Council G0501670Wellcome Trust
6 · The paper itself

Abstract

Plasmodium gene functions in mosquito and liver stages remain poorly characterized due to limitations in the throughput of phenotyping at these stages. To fill this gap, we followed more than 1,300 barcoded P. berghei mutants through the life cycle. We discover 461 genes required for efficient parasite transmission to mosquitoes through the liver stage and back into the bloodstream of mice. We analyze the screen in the context of genomic, transcriptomic, and metabolomic data by building a thermodynamic model of P. berghei liver-stage metabolism, which shows a major reprogramming of parasite metabolism to achieve rapid growth in the liver. We identify seven metabolic subsystems that become essential at the liver stages compared with asexual blood stages: type II fatty acid synthesis and elongation (FAE), tricarboxylic acid, amino sugar, heme, lipoate, and shikimate metabolism. Selected predictions from the model are individually validated in single mutants to provide future targets for drug development.

Indexed as

Genome, ProtozoanAllelesAmino SugarsAnimalsCulicidaeErythrocytesFatty AcidsFatty Acid SynthasesGene Knockout TechniquesGenotypeLife Cycle StagesLiverModels, BiologicalMutationParasitesPhenotypeAmino SugarsFatty AcidsFatty Acid Synthasesamino sugar biosynthesisfatty acid biosynthesisfatty acid elongationgenome-scale knockout screengenome-scale metabolic modelmalariametabolic modelmetabolic networkPlasmodium bergheiPlasmodium liver stage

Identifiers

PMID31730853
PMCPMC6904910

What OpenQuestion holds

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Registered trials

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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.