Cell based high-throughput screening, as a broad based small molecule drug screening tool, has been hampered by the lack of ability to quantitatively measure cellular changes in a reproducible, ultra-high-throughput manner. Genomic Signature Sequencing (GSS)™ provides the researcher with the means to use quantitative RNA measurements in cell based assays, across very large numbers of compounds, to monitor changes in tens of thousands of genes. This will enable rapid and cost effective monitoring of small molecule induced biological changes - at the cellular level - making the practical application of gene expression achievable in high-throughput compound screening laboratories.

The GSS application allows the researcher to customize the biological gene expression pathway to be interrogated. One might envision examining the small molecule perturbations of RNA expression signatures of disease specific pathways in a cell based assay. The researcher can optimize the cellular assay using biologically relevant cell lines which mimic the biological response seen in a disease relevant animal mode or human tissue in the hopes of introducing alterations which may restore the RNA expression profile to that which is seen in normal cells. The resulting "active" small molecules can then be more extensively studied for structure/function relationships in the search for new approaches to alter biological pathways which may provide insight into the treatment of human disease.

The GE-HTS application will:

• Allow the measurement of gene expression changes in subsets of genes across tens to hundreds of thousands of compounds per run
• Increase the ability to interrogate selected gene expression changes by two to three orders of magnitude compared to conventional assays
• Reduce the per RNA target price by an order of magnitude, compared to conventional biochemical and cell based assays