Fig. 4 | Nature Communications

Fig. 4

From: The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background

Fig. 4

Integrative analysis of artemisinin-resistant parasites. a Manhattan plot of GWAS for artemisinin resistance in e-GMS (upper) and w-GMS (lower). SNPs passing p-value < 1e−5 are displayed in black circles above dot lines. b Manhattan plot of TWAS for artemisinin resistance. Upregulated and downregulated genes displayed in two directions (Up and Down) were defined by positive and negative Spearman’s rho. The horizontal dotted lines represent p-value = 0.01 (Spearman’s rho test). Genes observed in both w- and e-GMS at p-value < 0.01 (Spearman’s rho test) and FDR < 0.25 (Benjamini & Hochberg correction) are black circled and labeled with gene name/id in the e-GMS plot. The relationships between parasite clearance time (pink blocks), gene expression (blue blocks) and SNP markers (yellow blocks) in e-GMS are characterized into five putative causality modes. c SNP affects clearance time dependent on expression and vice versa. d Clearance time and expression independently affects same SNP(s). e SNP affects clearance time independent of expression. f Expression mediated genetic effects on clearance time. g Expression affects clearance time independently of SNPs. Blocks are linked at p-value < 1e−05 for SNP-expression (eQTL) and SNP-clearance time (GWAS), and at p-value < 0.01 and FDR < 0.25 for expression-clearance time (TWAS). Corresponding gene/SNP name(s)/ID(s) or numbers are listed above blocks accordingly for each mode. Examples of resistance-associated relationships are shown in scatterplots with genes of farnesyltransferase (PF3D7_1242600) and thioredoxin-like (PF3D7_0717699) for mode c, 5′–3′ exonuclease (PF3D7_0204600) for mode d, 6-cysteine (PF3D7_0404900) and MDR1 (PF3D7_0523000) for mode f. Light blue used in scatterplots stand for isolates with reference alleles (ref.) and magenta for the alternative (alt). Expression is compared between alleles in boxplot on the right for each gene with the eQTL p-values labeled above

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