The modularity analysis of the network revealed four major modules whose functional annotation using GSEA supports the notion of modular organization underlying the network, the largest module with 2037 nodes is significantly enriched for regulation protein inhibitors of transcription, the second module with 1540 interconnected proteins is significantly involved in hormone and receptor signaling, the third module with 1420 proteins is significantly an notated for GPCR signaling, and finally the fourth module containing 1312 nodes is enriched for protein translation and induction of apoptosis. These findings are consistent with the fact that hor mone peptides are major ligands for GPCRs and through cellular signaling cascades, they regulate the transcription of target genes in the nucleus.

Evaluation of DHN by Inhibitors,Modulators,Libraries pathway recovery Both the biological relevance and the modularity were fur ther evaluated by mapping the Alzheimers disease pathway from the KEGG database as well as hormone signaling pathways from other resources. Mapping the Alzheimers disease pathway onto the network resulted in the recovery of all the proteins and their corresponding interactions in the pathway except for APH1A. Regarding hormone signaling pathways, the number of proteins involved in the actual signaling and the number of mapped proteins for each signaling pathway is shown in Table 2. For two pathways with 100% node recov ery, i. e. insulin signaling pathway and growth hormone pathway, manual extraction of edges from BioCarta and mapping them onto the network yielded 76% edge recovery for the growth hormone pathway and 90% edge recovery for the in sulin signaling pathway.

We also surveyed our network for the presence of hor mone receptors by comparing them Inhibitors,Modulators,Libraries to known hormone receptors of genomic neuroendocrine hormones and were able to identify them for majority of these hormones. Hormonal convergence in DHN After the completion of this individual pathway recovery test, we aggregated all the elements of these seven path ways and mapped them onto the giant component of DHN. The aim was to detect the core of DHN where the majority of hormone cross talks occur. A subnetwork of 73 nodes and 133 edges was formed, representing the converged hormonal pathway interactions. Interestingly, 62 of these hormone peptides are densely interconnected and form the core of DHN.

Besides, their interactions Inhibitors,Modulators,Libraries appeared to occur in different regions of the normal brain after adding the context of brain region an notations to each edge using the work of Bossi and Lehner. Inhibitors,Modulators,Libraries Analysis of these annotations shows that the majority of the Inhibitors,Modulators,Libraries hormonal interactions occur in prefrontal cortex, hypothalamus and cingulate cortex, respectively. The finding that interactions of the converged network mostly occur in prefrontal cortex and selleckchem cingulate cortex is consistent with the neuroanatomical distribution of neuro fibrillary tangles and plaques in the cerebral cortex of AD patients.