Pf7: An open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples

This record provides information about the Pf7 dataset which contains genome variation data on over 20,000 worldwide samples of Plasmodium falciparum. The key publication is MalariaGEN et al, Wellcome Open Research 2023, 8:22 https://doi.org/10.12688/wellcomeopenres.18681.1.

Content of the data release

This release contains details on contributing partner studies, sample metadata and key sample attributes inferred from genomic data, and genomic data including raw sequence reads. Further details and analytical results can be found in the accompanying data release paper.

These data are available open access. Publications using these data should acknowledge and cite the source of the data using the following format: "This publication uses MalariaGEN data as described in ‘Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples' MalariaGEN et al, Wellcome Open Research 2023, 8:22 https://doi.org/10.12688/wellcomeopenres.18681.1.

• Study information: Details of the 82 contributing partner studies, including description, contact information and key people.
• Sample provenance and sequencing metadata: sample information including partner study information, location and year of collection, ENA accession numbers, and QC information for 20,864 samples from 33 countries.
• Measure of complexity of infections: characterisation of within-host diversity (FWS) for 16,203 QC pass samples.
• Drug resistance marker genotypes: genotypes at known markers of drug resistance for 16,203 samples, containing amino acid and copy number genotypes at six loci: crt, dhfr, dhps, mdr1, kelch13, plasmepsin 2-3.
• Inferred resistance status classification: classification of 16,203 QC pass samples into different types of resistance to 10 drugs or combinations of drugs and to RDT detection: chloroquine, pyrimethamine, sulfadoxine, mefloquine, artemisinin, piperaquine, sulfadoxine- pyrimethamine for treatment of uncomplicated malaria, sulfadoxine- pyrimethamine for intermittent preventive treatment in pregnancy, artesunate-mefloquine, dihydroartemisinin-piperaquine, hrp2 and hrp3 gene deletions.
• Drug resistance markers to inferred resistance status: details of the heuristics utilised to map genetic markers to resistance status classification.
• CRT haplotypes: Full crt gene haplotypes for 16,203 QC pass samples. 
• CSP C-terminal haplotypes: Full csp C-terminal haplotypes for 16,203 QC pass samples plus 6 lab strains. 
• EBA175 calls: eba175 allelic type calls for 16,203 QC pass samples.
• Deletion and breakpoint locations with the histidine-rich protein genes II and III (HRP-2 and -3): List of deletion and breakpoint locations within the histidine-rich protein genes II and III (HRP-2 and -3) across 16,203 QC-pass samples. All samples with a deletion either have an exact breakpoint (in the case of samples where the deletion is due to telomere healing) or a breakpoint range (in the case of recombination with a different chromosome that has similar sequence).
• Mean pairwise F_ST between all major sub-populations
• Reference genome: the version of the 3D7 reference genome fasta file used for mapping. 
• Annotation file: the version of the 3D7 reference annotation gff file used for genome annotations. 
• Genetic distances: Genetic distance matrix comparing all 20,864 samples. 
• Chromosome-level VCF files containing variant calls all samples are available via the European Variation Archive (EVA) under analysis accession ERZ29886461 for all chromosomes except the mitochondrial chromosome, Pf_M76611, which is under analysis accession ERZ29886462

A README file describes in fine detail all the files included in the release, the format and interpretation of each column, and contains some tips and tricks for accessing genotype data in VCF and zarr files.

The following supplementary data is available as a single document download: Supplementary data:

• Supplementary Table 1. Breakdown of analysis set samples by geography
• Supplementary Table 2. Studies contributing samples
• Supplementary Table 3. Summary of discovered variant positions
• Supplementary Table 4. Numbers of samples used to determine proportions in Table 2.
• Supplementary Table 5. Newly emerging Dd2 background mutations in crt.
• Supplementary Table 6. Frequency of HRP2 and HRP3 deletions by country.
• Supplementary Table 7. Summary of hrp2 and hrp3 deletion breakpoints.
• Supplementary Figure 1. Breakdown of samples by country.
• Supplementary Figure 2. Distribution of samples by year of collection.
• Supplementary Figure 3. Lack of bias in population structure due to use of sWGA.
• Supplementary Figure 4. Population structure from a neighbour-joining tree.
• Supplementary Figure 5. Linkage disequilibrium decay in ten major parasite sub-populations.
• Supplementary Figure 6. Characteristics of the ten major parasite sub-populations.
• Supplementary Figure 7. Geographic patterns of population differentiation and gene flow.
• Supplementary Figure 8. Abacus plot of inferred drug resistance frequencies in location/year combinations.
• Supplementary Figure 9. Increase in frequency of KEL1.
• Supplementary Figure 10. Variation in c-terminal of csp.
• Supplementary Figure 11. Proportion of C allele of eba175 in different major sub-populations.