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100 genes (Supplementary Table 2). Modules were analyzed for over-representation of gene ontologies and illustrated by an unsupervised Cytoscape yFiles organic layout with each module color coded (Fig. 3a and Supplementary Table 2). We found 11 modules (out of 21) to be over-represented for various cellular biological pathways, particularly innate immune response (green module), type-I interferon signaling pathway (light yel- low module), synaptic signaling (red module), neurogenesis (black module) and extra- cellular matrix organization (magenta module) modules (Fig. 3a). Overlaying the fold
Figure 3 Co-expression network modules and miRNA target predictions. (a) Unsupervised weighted gene co-expression network analysis (WGCNA) showing over-represented gene ontol- ogy terms in TSC patients. (b) Overlay of fold expression (log2 tranformed) of differentially ex- pressed genes between TSC patients and controls on the gene co-expression network. Over-ex- pressed genes predominantly overlap with the innate immune response and extracellular matrix organization modules whereas under-expressed genes overlap with neurogenesis and glutamate receptor signaling module. (c) Graphical representation of over- and under-expressed genes en- riched within the over-represented co-expression network modules in TSC patients. Over-ex- pressed genes are predominantly associated with the innate immune response and extracellular matrix organization modules whereas under-expressed genes are predominantly associated with neurogenesis and glutamate receptor signaling modules. Only modules that harbored significant- ly different genes are illustrated. (d) The miR34 family (miR34a, miR34b and miR34c) target multi- ple targets in the neurogenesis and glutamate receptor signaling modules.