Identifying susceptibility networks for drug-induced non-immune neutropenia.

Abstract

Systems toxicology, a branch of toxicology that studies drug effects at the level of biological systems, offers exciting opportunities to discover toxicity-related sub-networks using high-throughput technologies. This paper takes a computational approach to systems toxicology and investigates the use of automated signalling path detection for discovery of potential biomarkers of drug-induced non-immune neutropenia. The algorithm utilises a gene expression change measure to mine a large protein interaction network and identify chemical-toxicity signalling paths. Cytoscape-based analysis of detected signalling paths with statistically significant path expression scores reveals 'hub' proteins and a smaller sub-network of path proteins. The importance of 'hub' and drug-toxicity signalling path proteins in haematological and apoptotic signal transduction networks is investigated in order to understand the value of automated signalling path detection approach.