There were 78 genes involved in these sets of 83, 133 and 277 putative cross-talks. We performed a similar Netwalker analyses with these 78 genes as we did for the dataset GSE38376, and found 37 genes (involved in 86 cross-talks (Additional file 14: Table S13)) consistent with our hypothesis that both genes in a particular cross-talk should be up-regulated in resistant conditions but down-regulated in parental conditions. In Figure 4, the selected genes from the secondary dataset exhibit an even clearer pattern of up-regulation in resistant conditions than the selected genes from our primary dataset.
Figure 4  Heatmap of genes in putative drug-resistant cross-talks in breast cancer cell-line: BT474 (GSE16179). Heatmap image of comparative gene expression changes of parental and resistant conditions in (A) all 78 genes in all 83, 133 and 277 putative drug-resistant cross-talks using signaling pathways from Reactome, KEGG and WikiPathway database, respectively, and (B) 37 selected genes based on their differential regulation. Here, for each gene, the expression value at each of the 4 conditions (2 parental conditions, and 2 resistant conditions) is the average value of 3 sample patients [16]. For each gene, these 4 expression values (each of them is the average of 3 samples) were transformed into z-scores (zero mean, unit standard deviation) and each z-score was normalized with the maximum absolute value of the z-scores across that particular gene. For both (A) and (B), red and green bars indicate up-regulation and down-regulation, respectively.