dc.contributor.authorZhu, Lei
dc.contributor.authorTripathi, Jaishree
dc.contributor.authorRocamora, Frances Maureen
dc.contributor.authorMiotto, Olivo
dc.contributor.authorvan der Pluijm, Rob
dc.contributor.authorVoss, Till S.
dc.contributor.authorMok, Sachel
dc.contributor.authorKwiatkowski, Dominic P.
dc.contributor.authorNosten, François
dc.contributor.authorDay, Nicholas P. J.
dc.contributor.authorWhite, Nicholas J.
dc.contributor.authorDondorp, Arjen M.
dc.contributor.authorBozdech, Zbynek
dc.identifier.citationZhu, 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-xen_US
dc.description.abstractThe 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.en_US
dc.format.extent13 p.en_US
dc.relation.ispartofseriesNature Communicationsen_US
dc.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/.en_US
dc.subjectDRNTU::Science::Biological sciencesen_US
dc.subjectPlasmodium Falciparumen_US
dc.subjectGreater Mekong Subregionen_US
dc.titleThe origins of malaria artemisinin resistance defined by a genetic and transcriptomic backgrounden_US
dc.typeJournal Article
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.description.versionPublished versionen_US

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