vasoactive-intestinal-peptide and Creutzfeldt-Jakob-Syndrome

We introduce a methodology to efficiently exploit natural-language expressed biomedical knowledge for repurposing existing drugs towards diseases for which they were not initially intended. Leveraging on developments in Computational Linguistics and Graph Theory, a methodology is defined to build a graph representation of knowledge, which is automatically analysed to discover hidden relations between any drug and any disease: these relations are specific paths among the biomedical entities of the graph, representing possible Modes of Action for any given pharmacological compound. We propose a measure for the likeliness of these paths based on a stochastic process on the graph. This measure depends on the abundance of indirect paths between a peptide and a disease, rather than solely on the strength of the shortest path connecting them. We provide real-world examples, showing how the method successfully retrieves known pathophysiological Mode of Action and finds new ones by meaningfully selecting and aggregating contributions from known bio-molecular interactions. Applications of this methodology are presented, and prove the efficacy of the method for selecting drugs as treatment options for rare diseases.

Topics: Benzamides; Computational Biology; Computer Graphics; Creutzfeldt-Jakob Syndrome; Drug Repositioning; Humans; Imatinib Mesylate; Models, Theoretical; Piperazines; Pyrimidines; Sarcoidosis; Vasoactive Intestinal Peptide