Figure 2

Functional analyses of differentially expressed genes in the artemisinin resistant parasites. (a) The heat maps depict differential gene expression in the trophozoite and schizont stages and the mean-centered log₂ ratios of mRNA levels between the resistant and susceptible isolates (for the complete set of all stages, see Additional file 6). Here the genes were ranked according to descending z-score (SNR) by correlating the expression profiles to the phenotypic class. Gene Set Enrichment Analysis (GSEA) revealed functional pathways down-regulated in trophozoites and up-regulated in schizonts of the resistant parasites shown in the side bar diagrams and ordered by the nominal p-value. Positions of the genes belonging to each identified pathway are indicated by the colored bars in the corresponding z-score ordered gene distribution. (b) Graphs illustrate several functional pathways with significant differential expression between the resistant and susceptible parasites in the three stages. Data points represent the average log₂ expression ratio for the isolates in each of the groups and across all genes belonging to the pathway for ring (14 hpi), trophozoite (26 hpi) and schizont (34 hpi) stages of the resistant (green triangle) and susceptible (blue diamond) isolates. Plotted are best fit polynomial curves and error bars that indicate the standard deviation amongst the isolates. Included are the average expression ratios for the artemisinin sensitive Cambodian isolate, CP022 (purple circle). For reference, the data are projected onto the centered mRNA abundance profiles of the in vitro IDC transcriptome (red square).