Functional network of selected upstream-regulators and differentially expressed genes across all tissues.

<p>From among the significant nodes identified using the Ingenuity Pathway Analysis® (IPA®) Upstream Regulator tool, the following were selected for inclusion in the displayed network: 1) the T-cell receptor (TCR), as this is the primary target of staphylococcal enterotoxin B (SEB)-mediated cell activation (colored orange at the network center); 2) TNF, IL-1β, IL-2, IFNγ and IL-12B, as these are known interferon (IFN) pathway initiators that were expressed early in the peripheral blood mononuclear cells and/or spleens of the SEB challenged mice (colored blue and positioned as the inner most ring of the network); and 3) any upstream regulator that was also present on our all-tissue list of differentially expressed genes (colored in shades of red proportional to fold-change) and positioned as the next ring moving outward. The resulting network connected 70 of 79 genes recognized by IPA®. The remaining 9 genes (outside of the outermost ring) were connected manually (see text) using PubMed and STRING (<a href="http://string-db.org/newstring_cgi/" target="_blank">http://string-db.org/newstring_cgi/</a>) version 9.05, a database of known and predicted protein-protein interactions. A key defining colors, shapes, and relationships is shown. In addition, changes in gene symbols from those in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088756#pone-0088756-g001" target="_blank">Figure 1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0088756#pone-0088756-t003" target="_blank">Table 3</a> are provided for clarity. Also note that IPA® frequently defaults to all-capital gene symbols that denote human genes, while elsewhere the mouse format is followed of only capitalizing the first letter.