An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples [version 1; peer review: 2 approved]

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed. Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination. This manuscript from the MalariaGEN consortium, a data-sharing community of teams working on Plasmodium falciparum genomic epidemiology, presents the new release of curated P. falciparum genomes from isolates collected in 73 locations in Africa, Asia, South America and Oceania. Based on robust and perfectly detailed methods (ranging from the treatment of the blood samples, the DNA extraction, the Illumina and computational platforms developed to produce genome sequencing for variant discovery and genotype calling), they analyzed 7000 P. falciparum genome sequences and provided numerous exciting data. For instance, they found that variations (SNPs and indels) in P. falciparum genome affected about a quarter of the 23 Mb genome (and mostly coding regions), or that duplication genotypes are frequent around mdr1, plasmepsin2/3 and gch1, which are known to be associated with antimalarial drug resistance (including mefloquine, piperaquine and sulfadoxine/pyrimethamine). Moreover, population genetic analyses conducted on this largest available data resource, depict a comprehensive picture of P. falciparum parasite populations globally and sub populations at continental level. In the results, a large section is devoted to the description of the geographic patterns of validated molecular markers (SNPs and CNVs) associated with antimalarial drug resistance. By compiling data on all samples collected from 2002–2015, they present clear profiles of drug resistance by regional sub-populations for the most used antimalarial drugs. Finally, they reveal a global landscape regarding a major challenge for malaria elimination, that are deletions in hrp2 and 3 genes linked The analysis of whole-genome sequences obtained from Plasmodium falciparum is particularly challenging due to the presence of hypervariable regions, highly repetitive sequences, and frequent mixture of parasites due to multiple infections of the host. The authors of this study describe a curated list of over three million high-confidence polymorphisms obtained from the genome sequence analysis of more than 7000 samples of P. falciparum collected by several studies in 73 locations in Africa, Asia, South America and Oceania. This work, reporting a laudable effort to substantially enrich publicly available genome data of P. falciparum worldwide, is of paramount importance for the field. The contribution goes in line with authors' previous consortia publications, extending largely the number of available data that can be analysed via web with powerful data analysis pipelines. By providing open access to a curated list of polymorphisms based on reproducible and high-quality protocols for the sequencing and analysis of P. falciparum genomes this study is likely to decrease the difficulties that have delayed the research on genomic epidemiology and population genomics of P. falciparum . Among other advances, studies in this area are likely to have important implications for a better understanding of the evolution towards drug resistance of the different global parasite populations ultimately contributing for a better control of this devastating disease. The manuscript is very well written and clear. It presents eight genetically distinct populations of parasites each endemic to different word regions, including South America, West Africa, Central Africa, East Africa, South Asia, West Southeast Asia, East Southeast Asia and Oceania. An interesting genetic and geographic characterization of the eight parasite populations is also shown. Of note, the finding of higher within-host diversity in the parasite populations endemic to Africa, the identification of single nucleotide polymorphism with high levels of geographic differentiation, and further characterization of geographic patterns of drug resistance and polymorphisms with potential