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

Approved or marketed small molecule and protein therapeutics for each of the differentially expressed proteins modulated by 5 or more respiratory viruses were obtained from the DrugBank database, version 3.0 (http://www.drugbank.ca/ accessed August 2011) [29] [30] [31] . We only considered those drugs that were launched products with experimental and clinical evidence of direct interaction with gene product in question. The therapy's interaction with the target and approved indication were identified using a combination of DrugBank, the drug manufacturer's information page, and the National Center for Biotechnology Information's PubChem (http://pubchem.ncbi.nlm.nih.gov/ accessed September 2011) [103] and Gene (http://www.ncbi.nlm. nih.gov/gene/ accessed September 2011) databases. Supplemental evidence of mechanism of action was obtained from immune or infection-related Jackson Laboratory knock-in/knock-out mouse (JAX) phenotype (http://www.jax.org/ accessed September 2011) [32] . (Table 3 ). The horizontal axis contains each of the 28 different comparisons labeled by virus, GSE and time point. The vertical axis shows the clustering of 27 genes from the top five and Parkin-UPS pathways that have an NVE of at least 6 and have an expression value in at least 26 comparisons. For genes present in more than one of the five pathways, the number of participating pathways is indicated by the count of ''*'' before the gene name. Color scheme is as described for Figure S3 . (TIF) Figure S5 Epidermal Growth Factor Receptor signaling pathway with viral frequency. Viral frequencies superimposed for each of most frequently differentially expressed proteins, where red circles are differential expression of genes by 7 viruses, orange circles are differential expression of genes by at least 6 viruses, and blue circles are differential expression of genes by 5 viruses. See MetaCore website at http://www.genego.com/pdf/ MC_legend.pdf for figure legend and Table S4 for pathway map gene products' corresponding HUGO gene names. (TIF) Figure S6 CD40 signaling pathway with viral frequency. Viral frequencies superimposed for each of most frequently differentially expressed proteins, where red circles are differential expression of genes by 7 viruses, orange circles are differential expression of genes by at least 6 viruses, and blue circles are differential expression of genes by 5 viruses. See MetaCore website at http://www.genego.com/pdf/MC_legend.pdf for figure legend and Table S4 for pathway map gene products' corresponding HUGO gene names. (TIF) Figure S7 Interferon-gamma signaling pathway with viral frequency. Viral frequencies superimposed for each of most frequently differentially expressed proteins, where red circles are differential expression of genes by 7 viruses, orange circles are differential expression of genes by at least 6 viruses, and blue circles are differential expression of genes by 5 viruses. See MetaCore website at http://www.genego.com/pdf/MC_legend. pdf for figure legend and Table S4 for pathway map gene products' corresponding HUGO gene names. (TIF) Figure S8 Histamine Receptor H1 signaling pathway with viral frequency. Viral frequencies superimposed for each of most frequently differentially expressed proteins, where red circles are differential expression of genes by 7 viruses, orange circles are differential expression of genes by at least 6 viruses, and blue circles are differential expression of genes by 5 viruses. See MetaCore w