Identification of Common Biological Pathways and Drug Targets Across Multiple Respiratory Viruses Based on Human Host Gene Expression Analysis

Smith, Steven B.; Dampier, William; Tozeren, Aydin; Brown, James R.; Magid-Slav, Michal

The NVEs for differentially expressed genes with frequencies of at least six viruses are shown in Table 3 along with their associated pathways. The list is ranked by the greatest viral frequency, and then by number of pathways in which the gene is differentially expressed. The NVE values for all genes, along with associated pathways, ranked by the greatest viral frequency, followed by the number of pathways in which the gene is differentially expressed are in Table S5 . We ensured that the NVE was not bias toward any particular comparison group, and indeed no single dataset contributed to the overall NVE for any single virus (Table S2) . Hierarchical clustering on the quantile normalized fold change values for all genes having expression values in at least 26 out of 28 comparisons (at least 90% comparisons) and significant in at least seven comparisons ( Figure S3 ) as well as for genes with NVE of at least six viruses ( Figure S4 ) did not reveal any dominant clustering by GSE or virus type. The most consistently up-regulated genes (up-regulated in at least six viruses and down-regulated no more than one virus) are: nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha (NFKBIA), tumor necrosis factor alpha-induced protein 3 (TNFAIP3), chemokine C-C motif ligand 2 (CCL2), interferon regulatory factor 1 (IRF1), prostaglandin-endoperoxide synthase 2 (PTGS2), chemokine C-C motif ligand 20 (CCL20), dual specificity phosphatase 1 (DUSP1), eukaryotic translation initiation factor 2-alpha kinase 2 (EI-F2AK2), TNF receptor superfamily member 6 (FAS), suppressor of cytokine signaling 1 (SOCS1), TNF receptor-associated factor 1 (TRAF1), and ubiquitin-conjugating enzyme E2L 6 (UBE2L6). There were no consistently down-regulated mRNAs (downregulated in at least six viruses and up-regulated in no more than one virus).