Pf6: An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples

This record provides information about the Pf6 dataset which contains genome variation data on 7,000 worldwide samples of Plasmodium falciparum. The key publication is MalariaGEN et al, Wellcome Open Research 2021642 DOI: 10.12688/wellcomeopenres.16168.1.  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 data from the MalariaGEN Plasmodium falciparum Community Project as described in ‘An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples. MalariaGEN et al, Wellcome Open Research 2021642 DOI: 10.12688/wellcomeopenres.16168.1.'". Study information: Details of the 49 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 7,113 samples from 28 countries. Measure of complexity of infections: characterisation of within-host diversity (FWS) for 5,970 QC pass samples. Drug resistance marker genotypes: genotypes at known markers of drug resistance for 7,113 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 5,970 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 genes deletions. Drug resistance markers to inferred resistance status: details of the heuristics utilised to map genetic markers to resistance status classification. Gene differentiation: estimates of global and local differentiation for 5,561 genes. Extended methods: detailed bioinformatic methods for Pf6. 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. Supplementary data The following supplementary data is available as a single document download: Supplementary data Supplementary Note Analysis of local differentiation score The classic 76T chloroquine resistance mutation in crt is found on multiple haplotypes Suplhadoxine-pyrimethamine resistance is widespread and associated with many haplotypes mdr1 duplications have many different breakpoints Artemisinin, piperaquine, and mefloquine resistance No evidence of resistance to less commonly used antimalarials 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. Breakpoints of duplications of gch1 Supplementary Table 5. Breakpoints of duplications of mdr1 Supplementary Table 6. Breakpoints of duplications of plasmepsin 2-3 Supplementary Table 7. Genes ranked by global differentiation score Supplementary Table 8. Genes ranked by local differentiation score Supplementary Table 9. Number of samples used to determine proportions in Table 2 Supplementary Table 10. Frequencies of mutations associated with mono- and multi-drug resistance pre- and post-2011 Supplementary Table 11. Frequency of crt amino acid 72-76 haplotypes Supplementary Table 12. Frequencies of dhfr (51, 59, 108, 164) and dhps (437, 540, 581, 613) multi-locus haplotypes Supplementary Table 13. Frequency of HRP2 and HRP3 deletions by country Supplementary Table 14. Alleles at six mitochondrial positions used for the species identification Supplementary Figure 1. Histogram of local differentiation score for all genes