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 differentially expressed gene lists from each comparison group were analyzed for enriched pathways using GeneGo. A pvalue for each of the 658 pathway maps in the MetaBase were generated for each comparison group using a hypergeometric test [99] . In order for a pathway to be considered enriched, each comparison group must contain pathways that have a p-value ,0.01 and occur in .5% of the total studies. The enriched pathway list was ranked by its viral frequency, which is defined by the number of viruses represented by at least one comparison group, and then by the sum of Normalized Viral Expression or NVE for each enriched pathway. The NVE for each pathway was calculated using the number of comparisons containing significant pathways within a virus type relative to the number of comparisons within that virus type. For example, if one out of four FLU comparisons for pathway A were significant, the NVE for FLU would be 1/4. Ranking the pathways in this fashion resulted in a clearer determination of pathways shared across multiple viruses, irrespective of time, strain type, or number of comparison groups.