Transcriptomic Characterization of the Novel Avian-Origin Influenza A (H7N9) Virus: Specific Host Response and Responses Intermediate between Avian (H5N1 and H7N7) and Human (H3N2) Viruses and Implications for Treatment Options

Josset, Laurence; Zeng, Hui; Kelly, Sara M.; Tumpey, Terrence M.; Katze, Michael G.

Connectivity map. To confirm whether drugs identified in IPA induce signatures opposite to those induced by IAVs, we used the publicly available Connectivity Map (Cmap) database (build 02) (45) . The Cmap is a collection of genome-wide transcriptional data from cultured human cells treated with 1,309 different compounds. We used the lists of DE genes up-and downregulated at each time point under each viral condition, limiting to the top 250 most up-and downregulated genes for lists containing a higher number of genes. Agilent probes were mapped to Affymetrix U133A probe sets using the BioMart ID converter tool (46) in order to query the Cmap database. Ten drugs out of the 26 potential antivirals identified in IPA were found in the Cmap database. We analyzed permuted results for drugs having consistent mean Cmap scores and enrichment scores (i.e., both scores were positive or both were negative). Relationships between drugs and viral signatures were depicted in a network using Cytoscape software and a circular layout (47) .