The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background
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-st...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2019
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| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/89113 http://hdl.handle.net/10220/47669 |
| _version_ | 1826122877064183808 |
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| author | Zhu, Lei Tripathi, Jaishree Rocamora, Frances Maureen Miotto, Olivo van der Pluijm, Rob Voss, Till S. Mok, Sachel Kwiatkowski, Dominic P. Nosten, François Day, Nicholas P. J. White, Nicholas J. Dondorp, Arjen M. Bozdech, Zbynek |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Zhu, Lei Tripathi, Jaishree Rocamora, Frances Maureen Miotto, Olivo van der Pluijm, Rob Voss, Till S. Mok, Sachel Kwiatkowski, Dominic P. Nosten, François Day, Nicholas P. J. White, Nicholas J. Dondorp, Arjen M. Bozdech, Zbynek |
| author_sort | Zhu, Lei |
| collection | NTU |
| description | 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. |
| first_indexed | 2024-10-01T05:55:45Z |
| format | Journal Article |
| id | ntu-10356/89113 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:55:45Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/891132023-02-28T16:56:47Z The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background Zhu, Lei Tripathi, Jaishree Rocamora, Frances Maureen Miotto, Olivo van der Pluijm, Rob Voss, Till S. Mok, Sachel Kwiatkowski, Dominic P. Nosten, François Day, Nicholas P. J. White, Nicholas J. Dondorp, Arjen M. Bozdech, Zbynek School of Biological Sciences Plasmodium Falciparum DRNTU::Science::Biological sciences Greater Mekong Subregion 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. Published version 2019-02-14T07:08:02Z 2019-12-06T17:18:09Z 2019-02-14T07:08:02Z 2019-12-06T17:18:09Z 2018 Journal Article 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 https://hdl.handle.net/10356/89113 http://hdl.handle.net/10220/47669 10.1038/s41467-018-07588-x en Nature Communications © 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/. 13 p. application/pdf |
| spellingShingle | Plasmodium Falciparum DRNTU::Science::Biological sciences Greater Mekong Subregion Zhu, Lei Tripathi, Jaishree Rocamora, Frances Maureen Miotto, Olivo van der Pluijm, Rob Voss, Till S. Mok, Sachel Kwiatkowski, Dominic P. Nosten, François Day, Nicholas P. J. White, Nicholas J. Dondorp, Arjen M. Bozdech, Zbynek The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| title | The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| title_full | The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| title_fullStr | The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| title_full_unstemmed | The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| title_short | The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| title_sort | origins of malaria artemisinin resistance defined by a genetic and transcriptomic background |
| topic | Plasmodium Falciparum DRNTU::Science::Biological sciences Greater Mekong Subregion |
| url | https://hdl.handle.net/10356/89113 http://hdl.handle.net/10220/47669 |
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