Mining Protein Interactions and Gene Expression Data to Gain Insights into Drug-induced Toxicity Mechanisms

In silico approaches for drug-induced toxicity evaluation are likely to enable improved screening of new chemical entities during drug discovery and development. Analysis of protein-protein interaction (PPI) networks using an edge centrality-based measure has previously been shown to reveal protein modules that may be associated with drug-induced toxicity. Here, we extend the algorithm by integrating protein interaction information with in vitro gene expression data from tissue treated with drugs known to be associated with the toxicity. We evaluate the new measure for its ability to detect non- immune neutropenia related proteins and propose a biomarker panel that may be valuable for screening future drug candidates.