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PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation.

Preston MD, Assefa SA, Ocholla H, Sutherland CJ, Borrmann S, Nzila A, Michon P, Hien TT, Bousema T, Drakeley CJ, Zongo I, Ou├ędraogo JB, Djimde AA, Doumbo OK, Nosten F, Fairhurst RM, Conway DJ, Roper C, Clark TG - J. Infect. Dis. (2013)

Bottom Line: The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies.The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting.The first release contains over 600,000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.

ABSTRACT
Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required. An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations. The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications. The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting. The first release contains over 600,000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).

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Related in: MedlinePlus

AMA1 vaccine candidate in chromosome 11. The apical membrane antigen 1 gene (AMA1, Chromosome 11, PF3D7_1133400) has long been recognised as a vaccine candidate and is currently being evaluated in clinical trials [22]. The high number of SNPs with intermediate MAF and low FST indicate that this locus is under balancing selection.
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JIT812F5: AMA1 vaccine candidate in chromosome 11. The apical membrane antigen 1 gene (AMA1, Chromosome 11, PF3D7_1133400) has long been recognised as a vaccine candidate and is currently being evaluated in clinical trials [22]. The high number of SNPs with intermediate MAF and low FST indicate that this locus is under balancing selection.

Mentions: Detecting balancing selection is one method to identify signatures of acquired immunity and therefore potential targets for vaccines. As immunity to the commonest alleles rises in malaria-endemic areas, parasites expressing rarer alleles experience a selective advantage. This process maintains a balance of alleles in the population, with neither the common alleles moving to fixation nor the rare alleles moving to extinction. When multiple alleles are maintained within populations and none of them achieves fixation, balancing selection forces are believed to be present. In PlasmoView, loci under balancing selection are readily be visualised as SNPs with intermediate MAF (10% to 40%) and low FST (indicating little population differentiation). These signatures are shown in vaccine targets previously identified using methods to detect balancing selection, including the MSP3.8 (merozoite surface protein 3.8, PF3D7_1036300, Supplementary Figure 2F) and AMA1 (apical membrane antigen 1, PF3D7_1133400) genes [11, 20, 21]. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on AMA1 and has been tested in clinical trials [22], see Figure 5.Figure 5.


PlasmoView: a web-based resource to visualise global Plasmodium falciparum genomic variation.

Preston MD, Assefa SA, Ocholla H, Sutherland CJ, Borrmann S, Nzila A, Michon P, Hien TT, Bousema T, Drakeley CJ, Zongo I, Ou├ędraogo JB, Djimde AA, Doumbo OK, Nosten F, Fairhurst RM, Conway DJ, Roper C, Clark TG - J. Infect. Dis. (2013)

AMA1 vaccine candidate in chromosome 11. The apical membrane antigen 1 gene (AMA1, Chromosome 11, PF3D7_1133400) has long been recognised as a vaccine candidate and is currently being evaluated in clinical trials [22]. The high number of SNPs with intermediate MAF and low FST indicate that this locus is under balancing selection.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4017360&req=5

JIT812F5: AMA1 vaccine candidate in chromosome 11. The apical membrane antigen 1 gene (AMA1, Chromosome 11, PF3D7_1133400) has long been recognised as a vaccine candidate and is currently being evaluated in clinical trials [22]. The high number of SNPs with intermediate MAF and low FST indicate that this locus is under balancing selection.
Mentions: Detecting balancing selection is one method to identify signatures of acquired immunity and therefore potential targets for vaccines. As immunity to the commonest alleles rises in malaria-endemic areas, parasites expressing rarer alleles experience a selective advantage. This process maintains a balance of alleles in the population, with neither the common alleles moving to fixation nor the rare alleles moving to extinction. When multiple alleles are maintained within populations and none of them achieves fixation, balancing selection forces are believed to be present. In PlasmoView, loci under balancing selection are readily be visualised as SNPs with intermediate MAF (10% to 40%) and low FST (indicating little population differentiation). These signatures are shown in vaccine targets previously identified using methods to detect balancing selection, including the MSP3.8 (merozoite surface protein 3.8, PF3D7_1036300, Supplementary Figure 2F) and AMA1 (apical membrane antigen 1, PF3D7_1133400) genes [11, 20, 21]. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1) based on AMA1 and has been tested in clinical trials [22], see Figure 5.Figure 5.

Bottom Line: The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies.The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting.The first release contains over 600,000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).

View Article: PubMed Central - PubMed

Affiliation: Department of Pathogen Molecular Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.

ABSTRACT
Malaria is a global public health challenge, with drug resistance a major barrier to disease control and elimination. To meet the urgent need for better treatments and vaccines, a deeper knowledge of Plasmodium biology and malaria epidemiology is required. An improved understanding of the genomic variation of malaria parasites, especially the most virulent Plasmodium falciparum (Pf) species, has the potential to yield new insights in these areas. High-throughput sequencing and genotyping is generating large amounts of genomic data across multiple parasite populations. The resulting ability to identify informative variants, particularly single-nucleotide polymorphisms (SNPs), will lead to the discovery of intra- and inter-population differences and thus enable the development of genetic barcodes for diagnostic assays and clinical studies. Knowledge of genetic variability underlying drug resistance and other differential phenotypes will also facilitate the identification of novel mutations and contribute to surveillance and stratified medicine applications. The PlasmoView interactive web-browsing tool enables the research community to visualise genomic variation and annotation (eg, biological function) in a geographic setting. The first release contains over 600,000 high-quality SNPs in 631 Pf isolates from laboratory strains and four malaria-endemic regions (West Africa, East Africa, Southeast Asia and Oceania).

Show MeSH
Related in: MedlinePlus