Figure 1

Overview of the approach applied in this study to predict diverging functional and regulatory interactions associated with the drug resistance transporter gene, pfcrt . Genes significantly correlated to pfcrt (FDR ≤ 0.20) in CQR or CQS recombinant clones were obtained using transcriptional data from the 24 hr developmental stage (trophozoites) [12]. Regulatory candidates associated with the pfcrt co-expression network in CQR or CQS parasites and functional partners of the gene were then predicted by applying the triangle inequality [22] based approach (TrIPI) developed in this study to assess the topological position of pfcrt correlated genes. Validations of the predicted regulatory and functional biological processes associated with pfcrt in CQR or CQS were then performed by measuring dose responses to small molecules targeting the processes. Additional information is provided in Additional file 1: section A.