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Figure 3 | BMC Systems Biology

Figure 3

From: Improvement of experimental testing and network training conditions with genome-wide microarrays for more accurate predictions of drug gene targets

Figure 3

Experimental methodology for fluconazole treatment experiments. (A) Wild-type yeast cells (BY4741) were treated with fluconazole (FL) at various exposure times and concentrations under constant growth conditions. (B) RNA purification, amplification and hybridization to Affymetrix YG S98 GeneChips were carried out and raw signal data was RMA-normalized and processed with SSEM-Lasso to determine residuals and subsequent ranks for all genes in the network. Two replicates for each condition were performed from two separate FL treatment experiments. (C) Gene set analysis detected gene perturbations of multiple, related genes across an increasing SSEM-Lasso rank threshold, resulting in a sensitivity vs. rank threshold curve (ROC curve) for each experimental condition. Area under each ROC curve was calculated, averaged for each duplicate experiment and reported as AUC%. AUC% values >0.5 (50%) indicated greater FL perturbation on the gene set. Gene set analyses were conducted for target pathway, FL-interacters (blue), and orthogonal pathways (purple). (D) Single gene analysis predicted FL perturbation on gene targets, ERG11, ERG6, UPC2 and HAP1, for every FL treatment condition. Target gene ranks were compared to the average ranks of six orthogonal genes. Low ranked genes were considered more accurately perturbed by FL. Ranks were averaged for two replicate experiments.

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