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

Existing computational strategies for compound target identification using gene expression profiles can generally be classified into two groups: comparative analysis and network-based analysis (4) . Comparative analysis methods use the gene expression profiles as drug signatures. Here, the similarity between the differential gene expression of a drug treatment and those of reference compounds or experiments with known targets, implies a closeness in the molecular targets and the MoA. A notable example of such an approach is the Connectivity Map (5) , which provides gene expression profiles of human cell lines treated by ∼5000 small molecule compounds as queryable signatures for evaluating drug-drug similarities (6) . The obvious drawback of comparative analysis methods is their dependence on an extensive and accurate target annotation of the reference gene expression profiles.