Bioinformatics techniques for disease detection and finding medical countermeasures: Case study with sulfur mustard
D. R. Gerecke1, M. Chen1, S. S. Isukapalli1, M. K. Gordon1, Y. C. Chang1, W. Tong2, I. P. Androulakis3, P. G. Georgopoulos1
1Environmental and Occupational Health Sciences Institute (EOHSI)
2U.S. Food and Drug Administration
3Department of Biomedical Engineering, Rutgers University
Sulfur mustard (HD, SM), is a chemical warfare agent that can penetrate human skin causing extensive blistering at the dermal-epidermal junction after a latency period of several hours. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the SM group from the control. Pathway analysis employing the KEGG library as well as Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Additional microarray experiments were conducted to assess the impact of an inhibitor (MMP-2/MMP-9 inhibitor) on the response to SM exposure. Subtle, but clearly identifiable differences in gene expression were noted when inhibitor was added. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.