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|Title:||The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background||Authors:||Zhu, Lei
Rocamora, Frances Maureen
van der Pluijm, Rob
Voss, Till S.
Kwiatkowski, Dominic P.
Day, Nicholas P. J.
White, Nicholas J.
Dondorp, Arjen M.
Greater Mekong Subregion
|Issue Date:||2018||Source:||Zhu, L., Tripathi, J., Rocamora, F. M., Miotto, O., van der Pluijm, R., Voss, T. S., . . . Bozdech, Z. (2018). The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background. Nature Communications, 9(1), 5158-. doi:10.1038/s41467-018-07588-x||Series/Report no.:||Nature Communications||Abstract:||The predisposition of parasites acquiring artemisinin resistance still remains unclear beyond the mutations in Pfk13 gene and modulation of the unfolded protein response pathway. To explore the chain of casualty underlying artemisinin resistance, we reanalyze 773 P. falciparum isolates from TRACI-study integrating TWAS, GWAS, and eQTL analyses. We find the majority of P. falciparum parasites are transcriptomically converged within each geographic site with two broader physiological profiles across the Greater Mekong Subregion (GMS). We report 8720 SNP-expression linkages in the eastern GMS parasites and 4537 in the western. The minimal overlap between them suggests differential gene regulatory networks facilitating parasite adaptations to their unique host environments. Finally, we identify two genetic and physiological backgrounds associating with artemisinin resistance in the GMS, together with a farnesyltransferase protein and a thioredoxin-like protein which may act as vital intermediators linking the Pfk13 C580Y mutation to the prolonged parasite clearance time.||URI:||https://hdl.handle.net/10356/89113
|DOI:||10.1038/s41467-018-07588-x||Rights:||© 2018 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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