Title: Identifying susceptibility networks for drug-induced non-immune neutropenia

Authors: Kaushal Desai; David Brott; Xiaohua Hu; Anastasia Christianson

Addresses: AstraZeneca Pharmaceuticals, Wilmington, DE 19850, USA ' AstraZeneca Pharmaceuticals, Wilmington, DE 19850, USA ' College of Information Science & Technology, Drexel University, Philadelphia, PA 19104, USA ' AstraZeneca Pharmaceuticals, Wilmington, DE 19850, USA

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.

Keywords: systems biology; gene expression change; protein interaction; systems toxicology; biomarkers; colour coding; bioinformatics; susceptibility networks; drug-induced neutropenia; non-immune neutropenia; signalling path detection; data mining; drug effects; haematological signal transduction networks; apoptotic signal transduction networks.

DOI: 10.1504/IJDMB.2015.066339

International Journal of Data Mining and Bioinformatics, 2015 Vol.11 No.1, pp.102 - 114

Received: 23 Feb 2013
Accepted: 25 Mar 2013

Published online: 17 Dec 2014 *

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