Precision drug repurposing via convergent eQTL-based molecules and pathway targeting independent disease-associated polymorphisms.

Precision drug repurposing via convergent eQTL-based molecules and pathway targeting independent disease-associated polymorphisms. Pac Symp Biocomput. 2019;24:308-319 Authors: Vitali F, Berghout J, Fan J, Li J, Li Q, Li H, Lussier YA Abstract Repurposing existing drugs for new therapeutic indications can improve success rates and streamline development. Use of large-scale biomedical data repositories, including eQTL regulatory relationships and genome-wide disease risk associations, offers opportunities to propose novel indications for drugs targeting common or convergent molecular candidates associated to two or more diseases. This proposed novel computational approach scales across 262 complex diseases, building a multi-partite hierarchical network integrating (i) GWAS-derived SNP-to-disease associations, (ii) eQTL-derived SNP-to-eGene associations incorporating both cis- and trans-relationships from 19 tissues, (iii) protein target-to-drug, and (iv) drug-to-disease indications with (iv) Gene Ontology-based information theoretic semantic (ITS) similarity calculated between protein target functions. Our hypothesis is that if two diseases are associated to a common or functionally similar eGene - and a drug targeting that eGene/protein in one disease exists - the second disease becomes a potential repurposing indication. To explore this, all possible pairs of independently segregating GWAS-derived SNPs were generated, and a statistic...
Source: Pacific Symposium on Biocomputing - Category: Bioinformatics Tags: Pac Symp Biocomput Source Type: research