Table 1.
P. vivax blood sample asexual profile and stage specificity.
Figure 1.
Gene expression patterns of 192 statistically significant cellular function clusters across all 41 P. vivax samples.
Each heat map row represents the common expression pattern shared by its cluster members and these profiles are hierarchically clustered so transcriptionally-related cellular functions are in close vicinity. For nine selected clusters with distinct life cycle expression profiles, the detailed gene-by-gene expression heat maps are shown to illustrate the high correlation within any given cluster. Additional evidences collected for each OPI cluster is summarized in a white-blue heat map. Blue color indicates a favorable piece of evidence, i.e., either the cluster members form statistically significant protein networks, or the OPI cluster was also found based on previous analyses and reanalyses of the published 54-sample P. falciparum and P. yoelii life cycle data set [10]. The average Pearson correlation coefficient of the expression profiles of P. falciparum orthologs of the cluster members are also color coded, so that blue represents a high positive correlation and gray represents a low negative correlation.
Figure 2.
Corresponding P. falciparum orthologs of the cluster members may form statistically significant two-hybrid interaction networks. Gene members known to be involved in the cluster are colored in green, predicted ones are colored in pink and those supported by OPI analyses of P. falciparum and P. yoelii life cycle data set are shown in blue. Interaction edges are color coded to reflect whether it is a direct interaction or an indirect interaction, and whether it has literature co-citation support or not. A complete list of genes with cross-validation is given in Table S3.
Figure 3.
Expression of metabolic genes in P. vivax asexual blood stage parasites.
The expression values of each gene in each sample were normalized by subtracting the average expression value and dividing by the standard deviation across all asexual samples. The glyceraldehyde 3-phosphate dehydrogenase gene is not annotated but the syntenic region in P. vivax also shows high expression in sample CM013 (Supplemental Figure 2). Gene expression values were normalized by subtracting the average expression value across all samples and dividing by the standard deviation of expression values across all samples. The resulting normalized expression values were colored on a scale ranging from −1 to +2, from black for the lowest, red for the middle, and white for the highest values. The gene ID numbers for glycolysis genes displayed in Figure 3 are: lactate dehydrogenase (PVX_116630, PF13_0141); enolase (PVX_095015, PF10_0155); glyceraldehyde 3-phosphate dehydrogenase (PVX_117321, PF14_0598); fructose 1,6-bisphosphate aldolase, putative (PVX_118255, PF14_0425); 2,3-bisphosphoglycerate-dependent phosphoglycerate mutase (PVX_091640, PF11_0208); triosephosphate isomerase (PVX_118495, PF14_0378). Gene ID numbers for TCA cycle and aerobic respiration genes are: flavoprotein subunit of succinate dehydrogenase (PVX_111005, PF10_0334); malate:quinone oxidoreductase (PVX_113980, PFF0815w); IRP-like protein (iron regulatory protein-like) (PVX_083005, PF13_0229); fumarate hydratase (PVX_099805, PFI1340w); ATP-specific succinyl-CoA synthetase beta subunit (PVX_084960, PF14_0295); 2-oxoglutarate dehydrogenase E1 component (PVX_089325, PF08_0045); dihydrolipoamide acyltransferase (PVX_119310, PFC0170c); succinyl-CoA synthetase alpha subunit (PVX_091100, PF11_0097); iron-sulfur subunit of succinate dehydrogenase (PVX_123345, PFL0630w); cytochrome C oxidase (PVX_099845, PFI1375w); cytochrome c oxidase copper chaperone (PVX_111430, PF10_0252); cytochrome c oxidase subunit II precursor (PVX_084995, PF14_0288); cytochrome c oxidase assembly protein (heme A: farnesyltransferase) (PVX_080280, PFE0970w); cytochrome c oxidase assembly protein (PVX_084785, PF14_0331); NADH dehydrogenase reaction protein (PVX_119700, PFC0505c).
Table 2.
Most highly expressed P. vivax genes in the sporozoite stage.
Table 3.
Genes showing the strongest probability of differential upregulation in zygotes.
Figure 4.
Co-expression of members of multigene families.
Our entire dataset as well as that of Bozdech (TP samples) from three samples of parasites taken into short term culture were combined and subjected to hierarchical clustering. A portion of the dendrogram is expanded. In contrast to other areas of the dendrogram almost all genes are hypotheticals or members of multigene families, may of which are likely to be exported. Gray areas indicate experiments for which no data is available.
Figure 5.
Sequence motifs associated with stage specific-expression.
A. Figure showing different motifs associated with different lifecycle stage expression. B. Alignment of promoter regions showing the sexual development motif. The motif TGTAnnTACA was discovered in GO:PM16005087 in 92 of the 364 genes promoter regions. While the majority of the 92 genes were hypothetical, the 22 with a predicted function are shown here. Distance is the number of bases upstream of the translational start site.