Figure 2

GSEA comparing REST target gene expression in glioma tumors and non-neoplastic brain. Gene set enrichment analysis results are shown comparing gene expression between 176 glioma tumors (of varying grade and type) and non-neoplastic brain (NCBI Dataset number GSE4290) over 3 independent lists of REST target genes. These results suggest that when compared to normal brain tissue, the glioma tumors in this dataset show a robust down-regulation of REST target genes. The FDR q-value and nominal p-value for each genelist suggest that such an enrichment of REST target gene expression in non-neoplastic tumors is unlikely to occur by random chance. GSEA was performed using 1,000 permutations utilizing a weighted enrichment statistic and a Signal2Noise metric for ranking genes. Genes with multiple probes were collapsed into a single gene using the max-probe value. The REST signature genelist is comprised of 24 genes that all contain REST binding sites and responded to REST knockdown with at least a two-fold up-regulation of target mRNA in three different cell lines, as previously described (Wagoner et al. 2010). The expanded REST genelist contains an additional 30 REST target genes that are up-regulated at least two-fold with loss of REST function in two of three cell lines. The 971 REST ChIP-Seq genes were determined by ChIP-Seq analysis from Jurkat t-cells by Johnson et al[3].