ArticleScientific reports2015
Chemogenomic profiling of Plasmodium falciparum as a tool to aid antimalarial drug discovery.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
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- MalariaSED: a deep learning framework to decipher the regulatory contributions of noncoding variants in malaria parasites.Genome biology · 2023Article
- A novel Modulator of Ring Stage Translation (MRST) gene alters artemisinin sensitivity inmSphere · 2023Article
- Chemogenomic Profiling of a Plasmodium falciparum Transposon Mutant Library Reveals Shared Effects of Dihydroartemisinin and Bortezomib on Lipid Metabolism and Exported Proteins.Microbiology spectrum · 2023Article
- Targeting Artemisinin-Resistant Malaria by Repurposing the Anti-Hepatitis C Virus Drug Alisporivir.Antimicrobial agents and chemotherapy · 2022Article
- Updated List of Transport Proteins inFrontiers in cellular and infection microbiology · 2022Review
- Paving the Way: Contributions of Big Data to Apicomplexan and Kinetoplastid Research.Frontiers in cellular and infection microbiology · 2022Review
- Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.International journal for parasitology. Drugs and drug resistance · 2021Article
- The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.Nature communications · 2021Article
- Improving gene network inference with graph wavelets and making insights about ageing-associated regulatory changes in lungs.Briefings in bioinformatics · 2021Article
- Genomic and Genetic Approaches to Studying Antimalarial Drug Resistance and Plasmodium Biology.Trends in parasitology · 2021Review
- Essential Genes of the Parasitic Apicomplexa.Trends in parasitology · 2021Review
- Targeting Gametocytes of the Malaria ParasitePathogens (Basel, Switzerland) · 2021Review
- Cellular thermal shift assay for the identification of drug-target interactions in the Plasmodium falciparum proteome.Nature protocols · 2020Article
- Altered expression of K13 disrupts DNA replication and repair in Plasmodium falciparum.BMC genomics · 2018Article
- High-throughput Identification of Synergistic Drug Combinations by the Overlap2 Method.Journal of visualized experiments : JoVE · 2018Article
- Uncovering the essential genes of the human malaria parasiteScience (New York, N.Y.) · 2018Article
- Knockout of the peroxiredoxin 5 homologue PFAOP does not affect the artemisinin susceptibility of Plasmodium falciparum.Scientific reports · 2017Article
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
The spread of Plasmodium falciparum multidrug resistance highlights the urgency to discover new targets and chemical scaffolds. Unfortunately, lack of experimentally validated functional information about most P. falciparum genes remains a strategic hurdle. Chemogenomic profiling is an established tool for classification of drugs with similar mechanisms of action by comparing drug fitness profiles in a collection of mutants. Inferences of drug mechanisms of action and targets can be obtained by associations between shifts in drug fitness and specific genetic changes in the mutants. In this screen, P. falciparum, piggyBac single insertion mutants were profiled for altered responses to antimalarial drugs and metabolic inhibitors to create chemogenomic profiles. Drugs targeting the same pathway shared similar response profiles and multiple pairwise correlations of the chemogenomic profiles revealed novel insights into drugs' mechanisms of action. A mutant of the artemisinin resistance candidate gene - "K13-propeller" gene (PF3D7_1343700) exhibited increased susceptibility to artemisinin drugs and identified a cluster of 7 mutants based on similar enhanced responses to the drugs tested. Our approach of chemogenomic profiling reveals artemisinin functional activity, linked by the unexpected drug-gene relationships of these mutants, to signal transduction and cell cycle regulation pathways.
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Registered trials
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.