Abstract

<p>‘Canonical’ pathways (such as those presented in a standard biochemistry textbook) are manually curated collections of protein interactions arranged in a manner that aids human understanding, and as artificial constructs the boundaries between pathways are subjective. Pathways that are conceptually distinct often have proteins in common and overlap, so in modular analysis, multiple pathways may collapse into a single module, causing other pathways and relationships to gain prominence. These two networks (<b>A</b> and <b>B</b>) represent those genes that are differentially expressed in melioidosis. For simplicity of presentation, we have used only a subset of genes in these networks. The top 221 upregulated genes (as ranked by <i>p</i>-value) are presented in <b>A</b>, and the top 155 downregulated genes are in <b>B</b>. The same clusters were found in an analysis of the whole gene set and those results are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054961#pone-0054961-t002" target="_blank">Tables 2</a> & <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054961#pone-0054961-t003" target="_blank">3</a>. <b>Network </b><b>A</b>. IFN-γ, TNF-α, IL-12 signalling pathways cluster together with the glypican network in the centre of the graph, but the complement/chemokine receptor (<b>cluster 1</b>), inflammasome (<b>cluster 2</b>) and Toll-like receptor pathways come to prominence in this analysis (<b>cluster 3</b>). <b>Network B</b>. IFN-γ, TGF-β and TNF signalling again cluster in the middle of the network. The two most prominent clusters are ribosomal proteins (<b>cluster 1</b>) and zinc finger proteins (<b>cluster 2</b>).</p

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