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O papel modulador do gene AIRE - capes

O papel modulador do gene AIRE - capes

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MANUSCRITO<strong>do</strong>wn regulated in mTEC cells. Figure 3 shows the <strong>gene</strong> expression hierarchicalclustering of statistically significant (SAM program) microarray data of controland Aire-silenced mTEC cells. It was possible to evidentiate 212 differentiallyexpressed PTA <strong>gene</strong>s, which 135 were induced in control mTECs andrepressed after Aire silencing.This <strong>gene</strong> data set was compared with GNF database allowing picturing thePGE featured by mTECs following the effect of Aire silencing. The PTA <strong>gene</strong>swere grouped in 17 body systems, which are represented in this mTEC cell line(Figure 4). It was possible to found that these 135 PTA <strong>gene</strong>s are under controlof the Aire <strong>gene</strong>, since its silencing caused their repression.Nevertheless, still remained the question about if the <strong>gene</strong>s, which featurePGE are connected in networks and what is the role of the Aire <strong>gene</strong> in theircontrol.Two widely used methods for microarray data analysis are the Cluster-and-Tree View (Eisen et al., 1989), which is based on a mathematical description ofsimilarity and the organization of <strong>gene</strong> expression data is realized by groupingtogether <strong>gene</strong>s with similar patterns of expression (hierarchical clustering), andthe Significance Analysis of Microarray (SAM) (Tusher et al., 2001), which isbased on t test statistics specifically developed for high-throughput microarraydata.Although these methods are useful tools for the identification of differentiallyexpressed <strong>gene</strong>s, they not permit the determination of interactions between<strong>gene</strong>s.There are several computational solutions proposed in the literature to infer<strong>gene</strong> networks; the approaches based on the mathematical formalism of the214

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