Browsing by Author "Amato, R."
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Item Genomic epidemiology of artemisinin resistant malaria(eLife, 2016-03) Awandare, G.A.; Amato, R.; Miotto, O.; Woodrow, C.J.; Almagro-Garcia, J.; Sinha, I.; Campino, S.; Mead, D. et.al.The current epidemic of artemisinin resistant Plasmodium falciparum in Southeast Asia is the result of a soft selective sweep involving at least 20 independent kelch13 mutations. In a large global survey, we find that kelch13 mutations which cause resistance in Southeast Asia are present at low frequency in Africa. We show that African kelch13 mutations have originated locally, and that kelch13 shows a normal variation pattern relative to other genes in Africa, whereas in Southeast Asia there is a great excess of non-synonymous mutations, many of which cause radical amino-acid changes. Thus, kelch13 is not currently undergoing strong selection in Africa, despite a deep reservoir of variations that could potentially allow resistance to emerge rapidly. The practical implications are that public health surveillance for artemisinin resistance should not rely on kelch13 data alone, and interventions to prevent resistance must account for local evolutionary conditions, shown by genomic epidemiology to differ greatly between geographical regions. © 2016, eLife Sciences Publications Ltd. All rights reserved.Item Major subpopulations of Plasmodium falciparum in sub-Saharan Africa(Science, 2019-08-23) Amenga-Etego, L.; Amambua-Ngwa, A.; Kamau, E.; Amato, R.; Ghansah, A.; Golassa, L.; Randrianarivelojosia, M.; Ishengoma, D.; Apinjoh, T.; Maïga-Ascofaré, O.; Andagalu, B.; Yavo, W.; Bouyou-Akotet, M.; Kolapo, O.; Mane, K.; Worwui, A.; Jeffries, D.; Simpson, V.; D’Alessandro, U.; Kwiatkowski, D.; Djimde, A.A.Understanding genomic variation and population structure of Plasmodium falciparum across Africa is necessary to sustain progress toward malaria elimination. Genome clustering of 2263 P. falciparum isolates from 24 malaria-endemic settings in 15 African countries identified major western, central, and eastern ancestries, plus a highly divergent Ethiopian population. Ancestry aligned to these regional blocs, overlapping with both the parasite’s origin and with historical human migration. The parasite populations are interbred and shared genomic haplotypes, especially across drug resistance loci, which showed the strongest recent identity-by-descent between populations. A recent signature of selection on chromosome 12 with candidate resistance loci against artemisinin derivatives was evident in Ghana and Malawi. Such selection and the emerging substructure may affect treatment-based intervention strategies against P. falciparum malaria.Item An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples(2021) MalariaGEN; Ahouidi, A.; Ali, M.; Almagro-Garcia, J.; Amambua-Ngwa, A.; Amaratunga, C.; Amato, R.; Amenga-Etego, L.; Andagalu, B.; Anderson, T.J.C.; Andrianaranjaka, V.; Apinjoh, T.; Ariani, C.; Ashley, E.A.; Auburn, S.; Awandare, G.A.; Ba, H.; Baraka, V.; Barry, A.E.; Bejon, P.; Bertin, G.I.; Boni, M.F.; Borrmann, S.; Bousema, T.; Branch, O.; Bull, P.C.; Busby, G.B.J.; Chookajorn, T.; Chotivanich, K.; Claessens, A.; Conway, D.; Craig, A.; D'Alessandro, U.; Dama, S.; Day, N.P.J.; Denis, B.; Diakite, M.; Djimdé, A.; Dolecek, C.; Dondorp, A.M.; Drakeley, C.; Drury, E.; Duffy, P.; Echeverry, D.F.; Egwang, T.G.; Erko, B.; Fairhurst, R.M.; Faiz, A.; Fanello, C.A.; Fukuda, M.M.; Gamboa, D.; Ghansah, A.; Golassa, L.; Goncalves, S.; Hamilton, W.L.; Harrison, G.L.A.; Hart, L.; Henrichs, C.; Hien, T.T.; Hill, C.A.; Hodgson, A.; Hubbart, C.; Imwong, M.; Ishengoma, D.S.; Jackson, S.A.; Jacob, C.G.; Jeffery, B.; Jeffreys, A.E.; Johnson, K.J.; Jyothi, D.; Kamaliddin, C.; Kamau, E.; Kekre, M.; Kluczynski, K.; Kochakarn, T.; Konaté, A.; Kwiatkowski, D.P.; Kyaw, M.P.; Lim, P.; Lon, C.; Loua, K.M.; Maïga-Ascofaré, O.; Malangone, C.; Manske, M.; Marfurt, J.; Marsh, K.; Mayxay, M.; Miles, A.; Miotto, O.; Mobegi, V.; Mokuolu, O.A.; Montgomery, J.; Mueller, I.; Newton, P.N.; Nguyen, T.; Nguyen, T.; Noedl, H.; Nosten, F.; Noviyanti, R.; Nzila, A.; Ochola-Oyier, L.I.; Ocholla, H.; Oduro, A.; Omedo, I.; Onyamboko, M.A.; Ouedraogo, J.; Oyebola, K.; Pearson, R.D.; Peshu, N.; Phyo, A.P.; Plowe, C.V.; Price, R.N.; Pukrittayakamee, S.; Randrianarivelojosia, M.; Rayner, J.C.; Ringwald, P.; Rockett, K.A.; Rowlands, K.; Ruiz, L.; Saunders, D.; Shayo, A.; Siba, P.; Simpson, V.J.; Stalker, J.; Su, X.; Sutherland, C.; Takala-Harrison, S.; Tavul, L.; Thathy, V.; Tshefu, A.; Verra, F.; Vinetz, J.; Wellems, T.E.; Wendler, J.; White, N.J.; Wright, I.; Yavo, W.; Ye, H.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.