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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.
Pubmed ID: 26541648 RIS Download
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Database of the most recent sequence updates and annotations for the P. falciparum genome. New annotations are constantly being added to keep up with published manuscripts and feedback from the Plasmodium research community. You may search by Protein Length, Molecular Mass, Gene Type, Date, Location, Protein Targeting, Transmembrane Helices, Product, GO, EC, Pfam ID, Curation and Comments, and Dbxrefs. BLAST and other tools are available. The P. falciparum 3D7 nuclear genome is 23.3 Mb in size, with a karyotype of 14 chromosomes. The G+C content is approximately 19%. The P. falciparum genome is undergoing re-annotation. This process started in October 2007 with a weeklong workshop co-organized by staff from the Wellcome Trust Sanger Intistute and the EuPathDB team. Ongoing curation and sequence checking is being carried out by the Pathogen Genomics group. Plasmodium falciparum is the most deadly of the five Plasmodium species that cause human malaria. Malaria has a massive impact on human health; it is the worlds second biggest killer after tuberculosis. Around 300 million clinical cases occur each year resulting in between 1.5 - 2.7 million deaths annually, the majority in sub-saharan Africa. It is estimated that 3,000 children under the age of five years fall victim to malaria each day. Around 40% of the worlds population are at risk. In collaboration with EuPathDB, genomic sequence data and annotations are regularly deposited on PlasmoDB where they can be integrated with other datasets and queried using customized queries.
View all literature mentionsDatabase of genomes at various stages of completion, from early access to partial genomes with automatic annotation through to complete genomes with extensive manual curation. Its primary goals are: 1) to provide reliable access to the latest sequence data and annotation/curation for the whole range of organisms sequenced by the Pathogen group, and 2) to develop the website and other tools to aid the community in accessing and obtaining the maximum value from these data.
View all literature mentionsThe SciCrunch Infrastructure was developed as a cooperative data platform to be used by diverse communities in making data more FAIR.
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