Author:

Abstract:

Many drugs exert their therapeutic activities through the modulation of multiple targets. Moreover, this polypharmacology is often associated with both beneficial and adverse off-target effects. For most drugs these targets are largely unknown and identification among the thousands of gene products remains difficult. Yet a better knowledge about such drug-protein interactions, along with the molecular pathways involved and the associated diseases, could be of substantial value to drug development, in particular to predict side effects and explore potential drug repositioning. DNA microarray technology enables us to observe the effect of drug treatment on the activity of all genes simultaneously and thus forms the perfect starting point for drug mode of action prediction. Hence we have developed an easy-to-use analysis suite for functional characterization of drugs based on gene expression changes following treatment. Our software provides all necessary tools for gaining new insights into the biological effects of a drug by integrating (1) preprocessing of gene expression data obtained from different Affymetrix array types; (2) quality assessment and exploratory analysis of these data; (3) genome-wide drug target prioritization; (4) prediction of pathways involved in the drug’s mode of effect; (5) identification of associated diseases enabling side effect prediction and drug repurposing; and (6) result visualization and reporting. Drug target prioritization is performed by means of an in-house developed algorithm for network neighborhood analysis, integrating the expression data with functional protein association information. All of the above functionalities are demonstrated on gene expression data for treatment with well-characterized drugs.