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

ProTINA is a novel and highly effective network-based analytical method for inferring the protein targets of compounds from gene expression profiling data. ProTINA combines the information of TF-gene and protein-protein interactions and data of differential gene expressions to create a tissue or cell type-specific PGRN model. Similar to network-based analysis methods such as NIR (7), MNI (8), SSEM (9) and DeltaNet (10), ProTINA uses a dynamic mechanistic model of the gene transcriptional process to compute deviations in the differential gene expression profiles that are induced by drug treatments. However, as mentioned earlier, the expression of the targets of a drug is often unaffected by the drug treatment (3) . For this reason and as illustrated in Figure 1C and D, ProTINA further transforms the deviations in the differential gene expression into alterations in the protein-gene regulatory edges in the PGRN model. Finally, the target scoring is based on edgetic perturbations of the PGRN, specifically enhancement or attenuation of gene regulatory interactions, caused by the compound.