Integration of population and functional genomics to understand mechanisms of artemisinin resistance in Plasmodium falciparum.

International Journal for Parasitology. Drugs and Drug Resistance
Jenna OberstallerShannon Takala-Harrison

Abstract

Resistance to antimalarial drugs, and in particular to the artemisinin derivatives and their partner drugs, threatens recent progress toward regional malaria elimination and eventual global malaria eradication. Population-level studies utilizing whole-genome sequencing approaches have facilitated the identification of regions of the parasite genome associated with both clinical and in vitro drug-resistance phenotypes. However, the biological relevance of genes identified in these analyses and the establishment of a causal relationship between genotype and phenotype requires functional characterization. Here we examined data from population genomic and transcriptomic studies in the context of data generated from recent functional studies, using a new population genetic approach designed to identify potential favored mutations within the region of a selective sweep (iSAFE). We identified several genes functioning in pathways now known to be associated with artemisinin resistance that were supported in early population genomic studies, as well as potential new drug targets/pathways for further validation and consideration for treatment of artemisinin-resistant Plasmodium falciparum. In addition, we establish the utility of iSAFE i...Continue Reading

References

Nov 12, 1996·Proceedings of the National Academy of Sciences of the United States of America·S J Darkin-RattrayD M Schmatz
Jun 17, 2000·International Journal for Parasitology·K T AndrewsP G Parsons
Oct 30, 2008·Nucleic Acids Research·Cristina AurrecoecheaHaiming Wang
Dec 10, 2008·The New England Journal of Medicine·Harald NoedlUNKNOWN Artemisinin Resistance in Cambodia 1 (ARC1) Study Consortium
Jan 28, 2009·International Journal for Parasitology·Werner LeberDavid A Baker
Jul 31, 2009·The New England Journal of Medicine·Arjen M DondorpNicholas J White
Feb 18, 2010·Antimicrobial Agents and Chemotherapy·Benoit WitkowskiFrançoise Benoit-Vical
May 21, 2010·Nature·Francisco-Javier GamoJose F Garcia-Bustos
Sep 24, 2010·PLoS Computational Biology·Thomas S RaskThomas Lavstsen
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nectarios KlonisLeann Tilley
Nov 26, 2011·Nucleic Acids Research·Flora J Logan-KlumplerMatthew Berriman
Mar 1, 2012·Sub-cellular Biochemistry·Thomas F J Martin
Apr 12, 2012·Science·Ian H CheesemanTimothy J C Anderson
Jul 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Daniel J ParkSarah K Volkman
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·Shannon Takala-HarrisonChristopher V Plowe
Apr 30, 2013·Nature Genetics·Olivo MiottoDominic P Kwiatkowski
Dec 20, 2013·Nature·Frédéric ArieyDidier Ménard
Sep 3, 2014·The Journal of Infectious Diseases·Shannon Takala-HarrisonChristopher V Plowe
Jan 20, 2015·Nature Genetics·Olivo MiottoDominic P Kwiatkowski
Jan 27, 2015·Annual Review of Biochemistry·Natalie J SpillmanDaniel E Goldberg
Jul 5, 2016·Nature Reviews. Microbiology·Tania F de Koning-WardPaul R Gilson
Mar 16, 2017·Cold Spring Harbor Perspectives in Medicine·Didier Menard, Arjen Dondorp
Feb 20, 2018·Nature Methods·Ali AkbariVineet Bafna

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Software Mentioned

topGO
SNPeff
Haplotype Caller
iSAFE
bioconductor
GATK
R

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