SBIR Phase I: A Deep Sequencing-Based Platform for Yeast Two-Hybrid Screening

SBIR 第一阶段：基于深度测序的酵母双杂交筛选平台

• 批准号: 1215608
• 负责人: Bernhard Suter
• 金额: $ 15万
• 依托单位: Quintara Biosciences, Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1215608&HistoricalAwards=false
• 关键词: SBIR; Phase; Deep; Sequencing; Based

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.

这个小型企业创新研究第一阶段项目涉及将Illumina的Solexa深度测序技术应用于酵母双杂交(Y2H)筛查。拟议的研究源于这样一种认识，即Y2H筛查的主要限制是缺乏对筛查结果的真正大规模读出。应用Illumina的深度测序方法全面分析汇集的Y2H菌株，将有效地取代传统方法所需的单个克隆的时间和劳动力密集型测序。此外，量体裁衣的计分方案将允许使用定量统计分析来确定Y2H读数的重要性。因此，深度测序技术的这种特殊增强不仅将极大地增加Y2H筛查的吞吐量(1,000-10,000倍)，而且还将提供对确定真正阳性结果的高度信心。这项研究的更广泛/商业影响将是向使用Y2H和相关程序进行筛查的强烈转变。一旦建立了这种Y2H筛查技术，研究人员将能够使用为转录组分析建立的工具和工作流程，识别和阐明基本上构成所有病理和复杂疾病的蛋白质-蛋白质相互作用的复杂网络。商业应用将以学术和工业实验室为目标，这些实验室希望探索药物靶标和癌基因的生物学背景。与传统的Y2H方法相比，建议的方法将以低得多的成本提供更好的结果。虽然Quintara在基因组应用方面的商机非常大，但真正的好处将增加到研究界和人类健康。