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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, Ouédraogo 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

Global distribution of the resistance-conferring PfCRT mutation K76T. The global prevalence of the K76T mutation (Chromosome 7, position 403 615) can be seen with the mutation fixed or close to fixed in most countries. Parasites may have reverted back to the wildtype allele, due to the complete withdrawal of chloroquine from some countries (eg, in East Africa, yellow on the left axis). The LAB Pf strains (laboratory-adapted and imported Pf strains) are located over the South Atlantic. Information on each bar chart is available by holding the cursor over it.
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JIT812F2: Global distribution of the resistance-conferring PfCRT mutation K76T. The global prevalence of the K76T mutation (Chromosome 7, position 403 615) can be seen with the mutation fixed or close to fixed in most countries. Parasites may have reverted back to the wildtype allele, due to the complete withdrawal of chloroquine from some countries (eg, in East Africa, yellow on the left axis). The LAB Pf strains (laboratory-adapted and imported Pf strains) are located over the South Atlantic. Information on each bar chart is available by holding the cursor over it.

Mentions: Drug resistance in Pf is commonly due to SNPs in genes involved in the biological pathways that antimalarials target. The matrix view in PlasmoView is ideally suited to display all observed mutations on a gene-by-gene basis. Figure 1 shows the mutations for each sample in PfCRT (PF3D7_0709000), a gene on chromosome 7 associated with chloroquine resistance [16]. Sixty-one SNPs (18 non-synonymous) have been detected in this gene, 5 of which are known to be involved in drug resistance. The high regional differentiation is measured by the SNP-wise FST (maximum 0.63, see blue histogram track in Figure 1). In PlasmoView the geographic spread of any mutation is further visualised in the map view, which displays SNP frequencies by geographical location. For example, Figure 2 shows the frequency of mutations observed across samples from each country at chromosome 7, position 403 615 (the PfCRT K76T amino acid mutation, [17, 18]). PlasmoView enables the easy identification of mutation sites within each gene, estimate their allele frequencies and investigate their geographical context, via the matrix view, the AF and FST graphs and the map view, respectively. The matrix views for three other genes (PfDHFR, PfDHPS and PfMDR1) involved in drug resistance are presented in Supplementary Figures 2A–C and also provided as part of the set of pre-loaded examples of interest for the web-browser.Figure 1.


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, Ouédraogo JB, Djimde AA, Doumbo OK, Nosten F, Fairhurst RM, Conway DJ, Roper C, Clark TG - J. Infect. Dis. (2013)

Global distribution of the resistance-conferring PfCRT mutation K76T. The global prevalence of the K76T mutation (Chromosome 7, position 403 615) can be seen with the mutation fixed or close to fixed in most countries. Parasites may have reverted back to the wildtype allele, due to the complete withdrawal of chloroquine from some countries (eg, in East Africa, yellow on the left axis). The LAB Pf strains (laboratory-adapted and imported Pf strains) are located over the South Atlantic. Information on each bar chart is available by holding the cursor over it.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

JIT812F2: Global distribution of the resistance-conferring PfCRT mutation K76T. The global prevalence of the K76T mutation (Chromosome 7, position 403 615) can be seen with the mutation fixed or close to fixed in most countries. Parasites may have reverted back to the wildtype allele, due to the complete withdrawal of chloroquine from some countries (eg, in East Africa, yellow on the left axis). The LAB Pf strains (laboratory-adapted and imported Pf strains) are located over the South Atlantic. Information on each bar chart is available by holding the cursor over it.
Mentions: Drug resistance in Pf is commonly due to SNPs in genes involved in the biological pathways that antimalarials target. The matrix view in PlasmoView is ideally suited to display all observed mutations on a gene-by-gene basis. Figure 1 shows the mutations for each sample in PfCRT (PF3D7_0709000), a gene on chromosome 7 associated with chloroquine resistance [16]. Sixty-one SNPs (18 non-synonymous) have been detected in this gene, 5 of which are known to be involved in drug resistance. The high regional differentiation is measured by the SNP-wise FST (maximum 0.63, see blue histogram track in Figure 1). In PlasmoView the geographic spread of any mutation is further visualised in the map view, which displays SNP frequencies by geographical location. For example, Figure 2 shows the frequency of mutations observed across samples from each country at chromosome 7, position 403 615 (the PfCRT K76T amino acid mutation, [17, 18]). PlasmoView enables the easy identification of mutation sites within each gene, estimate their allele frequencies and investigate their geographical context, via the matrix view, the AF and FST graphs and the map view, respectively. The matrix views for three other genes (PfDHFR, PfDHPS and PfMDR1) involved in drug resistance are presented in Supplementary Figures 2A–C and also provided as part of the set of pre-loaded examples of interest for the web-browser.Figure 1.

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