Diagnostic Microarray Test Based on Comparative Studies of Gene Expression in Humans with Common Inflammatory and Infectious Diseases

To assure accurate detection of exposure to biological warfare agents or any environmental agents, it is necessary to exclude a variety of common conditions that may confound proper diagnosis. Many groups, including ours, have found that biological warfare agents can stimulate inflammatory systems; the same systems found stimulated in common inflammatory diseases such as rheumatoid arthritis (RA), inflammatory bowel disease or ankylosing spondylitis (AS). Development of an accurate diagnostic tool therefore requires defining the changes in gene expression that are characteristic of these common inflammatory diseases in clinically accessible tissue and comparing them with the expression changes characteristic of exposure to biological warfare agents. Phase I of this project has been completed. Expression databases for rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, and hepatitis were compiled and will be provided to the Department of the Army for assessment of the disease-specific nature of the infectious disease data sets they have compiled. Moreover, we have employed a multivariate analysis method in preliminary studies to assess the feasibility of the approach and determined that the diagnostic signature of a given disorder can be defined using only 36 genes in total. In Phase 2 we will continue our ongoing integrated development efforts to create a practical high throughput assay. This works includes continued development and optimization of class selection algorithms, normalization strategies, and high throughput HTPscreening methods. In preliminary investigations we have created novel class prediction methods, a sound theoretical foundation for data normalization suitable for assay development, and a HTP method for gene expression analysis. These essential components will be optimized, integrated, and a fully tested prototype assay developed at the end of this phase of the project.