This Small Business Innovation Research Phase I project concerns applying Illumina's Solexa deep-sequencing technology as a read-out for yeast two-hybrid (Y2H) screens. The proposed research arose from the recognition that the principal limitation of Y2H screening is the lack of a true large-scale readout for the screening results. Applying Illumina's deep-sequencing methodology to comprehensively analyze pooled Y2H strains will effectively supplant the time- and labor-intensive sequencing of individual clones required by conventional approaches. Further, a tailored scoring scheme will allow use of quantitative statistical analysis to determine the significance of the Y2H readouts. Hence, this particular enhancement of deep-sequencing technology will not only vastly increase the throughput of Y2H screens (1,000-10,000 fold), but will also provide high confidence in identification of true positive results. The broader/commercial impact of this research will be a strong shift towards using Y2H and related procedures for screening. Once this Y2H screening technology is established, researchers, using tools and workflows set up for transcriptome analysis, will be able to identify and elucidate the intricate networks of protein-protein interactions that underlie essentially all pathologies and complex diseases. Commercial applications will target academic and industrial labs that wish to explore the biological context of drug targets and oncogenes. Compared with conventional Y2H methods, the proposed approach will deliver superior results at a much lower cost. While the business opportunity for Quintara for genomics applications is very large, the real benefits will accrue to the research community and human health.
