Development of Predictive Algorithms for In Silico Drug Toxicity and Efficacy Assessment

"The need to screen drug candidates earlier in the discovery process to prevent costly failures during the clinical stages has motivated in the development of in silico tools for drug screening based on toxicity. Most of the existing approaches do notconsider the integrated nature of the metabolic network. In the current proposal, we intend to use approaches from a systems biology perspective to develop tools for toxicity prediction. The feasibility of the use of constraints-based models of cellularmetabolism for the prediction of toxicity would be evaluated in the Phase I proposal. Upon the completion of this SBIR project, we expect to have successfully developed technologies that can be used for evaluating the toxicity od specific drugs. Thescope of the toxicity assessment can be expanded by considering functional groups of several drugs along with the associated effects on the human metabolic network. Protein-drug interaction data along with gene expression data can be incorporated into theanalysis to further widen the scope for toxicity evaluation. The proposed research will ultimately result in a novel computational tool for toxicity prediction based on the genome scale analysis of metabolic networks. This tool can also be used toidentify new drug targets, provide alternatives to intractable drug targets, prioritize candidate drug targets to establish optimal points for therapeutic intervention, and to develop assays for t