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.

Upstream regulator analysis, which was used to predict regulators and infer their activation state, is based on prior knowledge of expected effects between regulators and their known target genes according to the IPA database. A z score is calculated and determines whether gene expression changes for known targets of each regulator are consistent with what is expected from the literature (z score Ͼ 2) or if the changes are anticorrelated with the literature (z score Ͻ Ϫ2). To predict potential antivirals, we queried the IPA database with the list of DE genes at each time point for each IAV, and we selected the molecules annotated "chemical drug," "biologic drug," "chemical-kinase inhibitor," or "chemical-protease inhibitor" having a z score of ϽϪ2 on at least 2 time points and no positive z score at other time points.