Figure 4

Clusters with variant expression and association with clinical phenotypes. (A) Measures of variant expression in vivo and in vitro. Shown is a heat map with clusters enriched in variantly expressed genes based on both field and in vitro arrays (left), or based on H3K9m³ histone modification (right) (see Methods; Additional file 1). Note that only clusters 23 and 44 share all the three phenotypes, as marked with red arrows. Clusters with variant expression pattern across patient samples in the Malawi cohort are marked with black arrows. Black arrowheads: clusters with enrichment in genes with H3K9m³ marks. (B) Asexual parasite stage in field samples. Distribution of parasite stages in the Senegal (left) and Malawi (right) cohorts shows that the majority of parasites in both cohorts are at 10 h post invasion. (C) Clinical phenotypes and correlations with clusters. Shown are those clinical parameters from the Malawi cohort with at least one significant cluster association (q-value ≤0.05 by aggregate Kruskal-Wallis statistic or Spearman correlation; see Methods, Additional file 9). (D) Correlations with parasite stage. Parasitemia and gametocytemia are shown for each sample (left panel). Stage distribution of genes in the two transcriptional groups (A and B) as defined by Milner et al. [26] is presented in the left panel. WBC, white blood cell.