DrugBank selleck chem was searched for the proteins of the core DHN as targets of approved drugs. Then PubMed was searched for supporting evidence of positive off target effects of non dementia drugs that showed poten tial implication of those drug targets in improvement of dementia. Results Enrichment of dementia related proteins for hormone signaling activity Mining the knowledge space of the literature for proteins that are shown to play a role in dementia resulted in a list of 1960 entities, which were ranked based on their mutual information. Due to the fact that high dimensional information returned by retrieval systems in herits noise, the next step was to observe whether signals of hormonal proteins could be detected in this large list of entities.

The gene set enrichment analysis of these proteins revealed under represented signatures of hormone activities in pathway analysis as well as implicit but statisti cally significant presence of hormone related regulatory gene sets in GO biological process annotations. However, at the level of GO molecular function, these signatures Inhibitors,Modulators,Libraries showed significant over representation for hormone activity, neuropeptide hormones and hormone signaling pathways. The results of this observation led us to raise the hypoth esis that an endocrine interaction network may exist that substantially Inhibitors,Modulators,Libraries contributes to the pathology of the dementia spectrum diseases. To investigate this hypothesis, we used text mining and knowledge discovery technologies to nar row down our search for retrieval and extraction of in stances of hormone proteins and their receptors, which are cited in the literature in relation to de mentia.

The focused search resulted in retrieval of 1329 documents and 453 protein entities extracted from them. Inhibitors,Modulators,Libraries Finally, Inhibitors,Modulators,Libraries 89 hormone hormone receptor entities were con firmed to play a role as hormone hormone receptor after crosschecking the retrieved entities with the contents of the EndoNet database as gold standard. We use this initial set of proteins as prior knowledge to build upon our integrative model. Dementia related hormone network and its biological relevance The initial protein protein interaction Inhibitors,Modulators,Libraries network comprises of 6966 nodes and 85997 selleck chemicals llc edges but after filtering the number of edges in DHN decreased to 83998. 6515 nodes form a giant connected component and the rest of 451 nodes are singletons without any connection, thus, for simplicity, we only consider the giant component for further analyses. Statistical analysis of the giant component of DHN shows that its node de gree distribution could be fitted in the power law of the form y 1092. 8 �� 1. 17 with an acceptable goodness of fit. This indi cates that the network is of biological nature. The network clustering coefficient of 0.