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

Besides its intended use to predict targets of compounds, we also demonstrated that the analysis of network perturbations using ProTINA could provide insights into the mechanism of diseases. In the application to gene expression profiles of Calu-3 cells from influenza A infection studies, ProTINA again outperformed DeMAND and DE analysis in identifying host factors that bind with viral proteins. Furthermore, the GSEA of ProTINA target predictions revealed the spectrum of cellular processes involved in the early phase of influenza A infection, including pathways involved in viral entry, replication and assembly, and those related to cellular response to viral infection. Among the pathways with the highest significance (lowest q-value) was focal adhesion, which has been shown to regulate influenza viral entry as well as viral replication (70) . Meanwhile, the target predictions of DeMAND and DE analysis had fewer enriched pathways, and thus were less informative than the target analysis by ProTINA.