Figure 3.

Individual gene expression values from representative clusters associated with parasite phenotypes. (A) Differential expression of ring stage clusters. Based on the mean transcript abundance as calculated in Figure 2, differential expression of ring stage clusters (mean peak time ≤22 hours) was determined by combined t-statistic (see Methods) of in vitro parasite time points between 0 and 22 hours post-invasion versus each in vivo dataset. Most clusters that are up-regulated in patient isolates are enriched in genes involved in expression regulation (transcription, translation, protein degradation; red asterisks), while some clusters enriched in exported proteins are up-regulated in patient samples and others are down-regulated (black asterisks). Clusters are ranked as in Figure 2. (B) Differential gene expression between patient cohorts. Each row corresponds to one gene, and each column represents a patient sample. Clusters 18 and 23 are up-regulated in isolates from patients with cerebral malaria compared with those from patients with uncomplicated malaria (aggregate t-statistic across genes in cluster). These clusters are highly enriched in secreted parasite antigens, including RESA, RESA2, LSA3, LSAP, ACS11, and GEXP20 as well as several ETRAMP and PHIST proteins.