ecificity of the Conserved network increased up to two fold with PCC values, suggesting that gene pairs with high PCCs in the Conserved net work are likely to be well useful handbook annotated molecular entities. All genes in the Conserved network were processed further by MCL clustering. There were 302 clusters, of which six contained 40 genes. The largest cluster consisted of 245 genes. Enrichment of each MCL cluster for GO Biological Process terms identi fied processes such as tRNA aminoacylation for protein transport, Cell division, and Pro tein transport. At the gene level, the Conserved network was representative of GO BP terms such as Regulation of transcription, Transport, and Signal transduction, as well as KEGG pathways such as Focal adhesion, MAPK signaling pathway, and Neuroactive ligand receptor interaction.

The generation of a Conserved network for physiologi cal cardiac hypertrophy consisting of 2128 genes and 4144 interactions, based on a series of relevant microarray experiments and computational processing of gene expression similarities, is thus a first step towards the discovery of the molecular underpinnings of this phenotype, its basic components and their structural and functional features. Identification of Critical Hubs in the Conserved co expression Network The topology of the Conserved network was explored further to identify hub genes. Betweenness centrality and node degree were measured for 2128 genes. There were 1020 genes with high betweenness centrality, connected by 3047 interactions.

These 1020 genes formed the core of the Conserved network mainly because changes in their expression and or structure are likely to alter behavior and topology of the overall network. Remarkably, 96 out of 1020 genes had both high betweenness centrality and node degrees. These genes tended to localize at the center of the net work, while the other 924 genes aligned along the periph ery. The three genes with the greatest values for both topological parameters were Nfs1, Shfm1, and Rnf13. It is inter esting to note that Nfs1 is an aminotransferase with a cysteine desulfurase function implicated in Freidrichs ataxia, a complex disease often associated with a hypertrophic cardiomyopathy phenotype. Furthermore, Shfm1 is the gene most likely associated with Split hand GSK-3 split foot malformation in region 7q21. 3 q22. 1, a disease exhibiting congenital heart defect phenotypes.

Finally, Rnf13 is a trans membrane RING type E3 ubiquitin ligase highly expressed in pancreatic ductal adenocarcinoma, but also expressed in chicken embryo brain and heart. It follows that most of the other 96 genes uncovered by using the above mentioned topological parameters might also be implicated in expression patterns with lower a pheno type associated with heart tissue. To test the hypothesis that hub genes may be crucial to the overall structure of the discovered network, the 200 most connected genes were systematically removed from the network. To assess network integrity, average be