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

There were 67 enriched pathways in which all seven respiratory viruses were represented by at least one comparison group (Table S3 ). The list is ranked first by the viral frequency, followed by the sum of the normalized viral expression (NVE) for each pathway. Also shown are the differentially expressed as well as the total number of network objects across all 28 comparisons. The top 20 enriched pathways are listed in Table 2 along with the percentage and names of the differentially expressed genes with a viral frequency of at least five in each pathway. Of these, the top five pathways were chosen for further analysis and mapping. These pathways are epidermal growth factor receptor (EGFR) signaling, CD40 signaling, interferon-gamma (IFNG) signaling, histamine receptor H1 (HRH1) signaling, and interleukin-17 (IL17) signaling (Figures S5. S6, S7, S8, S9; Table S4 ). Additionally, the Parkin-Ubiquitin Proteasomal System (Parkin-UPS) pathway was chosen for further analysis because it has not been previously associated with the innate immunity and might be an interesting new mechanism of host response to respiratory viral infection ( Figure 3 ).