Prediction of novel drug indications using network driven biological data prioritization and integration

Abstract

Abstract Background With the rapid development of high-throughput genomic technologies and the accumulation of genome-wide datasets for gene expression profiling and biological networks, the impact of diseases and drugs on gene expression can be comprehensively characterized. Drug repositioning offers the possibility of reduced risks in the drug discovery process, thus it is an essential step in drug development. Results Computational prediction of drug-disease interactions using gene expression profiling datasets and biological networks is a new direction in drug repositioning that has gained increasing interest. We developed a computational framework to build disease-drug networks using drug- and disease-specific subnetworks. The framework incorporates protein networks to refine drug and disease associated genes and prioritize genes in disease and drug specific networks. For each drug and disease we built multiple networks using gene expression profiling and text mining. Finally a logistic regression model was used to build functional associations between drugs and diseases. Conclusions We found that representing drugs and diseases by genes with high centrality degree in gene networks is the most promising representation of drug or disease subnetworks.