Two HB subnetworks: associated with severe versus mild spectrum disease. HB networks reveal two discrete HB subsets—one being associated with severe spectrum phenotypes (orange) and the other being associated with mild spectrum phenotypes (blue). (A) The network of significant positive linkage disequilibrium coefficients (D) among HBs in the genomic dataset, based on a one-tailed significance threshold of p ≤ .025, reveals two subnetworks of linked HBs. (B) The network of significant associations between HB expression rates and phenotypes (p ≤ 0.05) with nodes colored according to the subnetworks of A. The HBs in the orange subnetwork are generally associated with severe disease spectrum phenotypes, whereas those in the blue subnetwork are generally associated with mild. The lack of connectivity between the severe and mild spectrum phenotypes in A is highly significant: even just considering the nodes of degree 3 or less, p < 0.0001 for the fact that each HB in the network is associated with mild or severe spectrum phenotypes, but not both. SMA = severe malarial anemia, Rosett = rosetting, RD = respiratory distress, Severe = severe disease, Mild = mild disease, Older = high host age, Younger = low host age, Par = parasitemia, BGlu = blood glucose (low levels indicate hypoglycemia), BaseE = base excess (low levels indicate metabolic acidosis), AB = antibody response.