Network perturbation analysis of gene transcriptional profiles reveals protein targets and mechanism of action of drugs and influenza A viral infection

Noh, Heeju; Shoemaker, Jason E; Gunawan, Rudiyanto

As illustrated in Figure 4A , DeMAND and DE analysis also performed reasonably well in predicting the com-pounds' MoA. But, the directions of the perturbations predicted by DE analysis were not always consistent with the expected response to DNA damage (see Supplementary Table S5 and S6). Meanwhile, DeMAND did not provide any information on the directions of the drug perturbations. In addition, the protein target scores of ProTINA provided a clearer demarcation between the genotoxic and the nongenotoxic agents among the compounds in the dataset, than DeMAND and DE analysis (see Supplementary Figure S1 ). Besides the canonical p53 response pathway, we further looked at the ranking of proteins involved in the overall DNA damage repair (DDR) and its associated pathways (56) (see Supplementary material 2). As depicted in Figure 4B , ProTINA ranked these proteins much higher than De-MAND and DE analysis, with DE performing the poorest among the methods considered.