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The search for mRNA biomarkers: global quantification of transcriptional and translational responses to ionising radiation

¹ Bridgeport Hospital, Bridgeport, and Yale University School of Medicine, New Haven, CT, USA, ² Chemical Computing Group, Montreal, Quebec, Canada and ³ Yale New Haven Health System Center for Emergency Preparedness and Disaster Response, New Haven, CT, USA

Correspondence: Nicholas Dainiak, MD, Department of Medicine, Bridgeport Hospital, 267 Grant Street, Bridgeport, CT 06610, USA. E-mail: pndain@bpthosp.org

Since the discovery of X-rays and the subsequent realisation that ionising radiation (IR) can provide a curative mode of therapy to treat tumours, there has been a concerted effort to discover the mechanisms by which IR induces cells to die or to become resistant to radiotherapy. Classical genetic analyses and biochemical techniques have been used to identify an ever-expanding number of genes whose activation directly or indirectly influences DNA repair, cell cycle progression and apoptosis. The advent of cDNA microarrays provides an opportunity to explore further the biological processes fundamental to the radiation response by permitting a comprehensive assessment of a cell's transcriptional landscape. The capacity to study the expression patterns of thousands of genes simultaneously may lead to (i) an increased understanding of how IR-responsive genes from seemingly mutually exclusive pathways (i.e. DNA repair and apoptosis) interact to determine the fate of irradiated cells and (ii) the discovery of new biomarkers for radiation exposure. Still in its infancy, protein microarray technology provides a complementary approach to cDNA microarray techniques for studying protein expression following exposure to IR. Analysis of microarrays requires a basic understanding of hierarchical clustering methodologies. Projection pursuit is one such method that shows promise in analysis of the non-linear data that are often generated from microarrays.