Ordered Arrays for Advanced Sequencing Systems

描述(申请人提供)：下一代测序技术的出现使研究人员能够进行研究并发现以前在经济上或技术上不可行的东西。然而，到目前为止，更高吞吐量的下一代测序系统相对昂贵，运行时间相对较长，产生的读数相对较短，从而限制了它们在诊断应用中的使用。在这一第二阶段的应用中，我们建议将第一阶段开发的新型芯片制造技术、哥伦比亚大学独家授权的创新合成化学测序技术和自动原型测序仪器相结合，以产生先进的合成测序系统。与其他竞争的下一代技术相比，该系统将具有更高的吞吐量和更高的成本效益。在该项目期间，将制造高密度芯片，优化测序仪器和化学，并对大肠杆菌基因组进行重新测序。该系统将能够以比任何其他近期下一代测序系统更快和更低的成本产生大量高质量的序列数据。这将使下一代DNA测序技术更容易为广大研究社区所接受。 与公共卫生相关：最终，能够为复杂生物的基因组产生非常廉价的详细DNA序列信息，将加速整个生物学的发现，并为药物基因组学提供基础，药物基因组学是一种治疗学中的新范式，根据个体基因型别而不是仅根据观察到的症状来开药。

DESCRIPTION (provided by applicant): The advent of next-generation sequencing technologies is allowing researchers to perform studies and make discoveries which previously were not economically or technically feasible. Thus far, however, higher-throughput next-generation sequencing systems are relatively expensive, have relatively long run times and produce relatively short reads thereby limiting their use for diagnostic applications. In this Phase II application, we propose to combine the novel chip fabrication techniques developed in Phase I, the innovative sequencing by synthesis chemistry exclusively licensed from Columbia University, and an automated prototype sequencing instrument to produce an advanced sequencing by synthesis system. This system will be higher throughput and significantly more cost effective than other competing next-generation technologies. During the project, high density chips will be fabricated, the sequencing instrument and chemistry will be optimized and an E. coli genome will be re-sequenced. This system will be capable of producing large amounts of quality sequence data faster and at a lower cost than any other near-term next generation sequencing system. This will make next-generation DNA sequencing technology more accessible to the broad research community. PUBLIC HEALTH RELEVANCE: Ultimately, the ability to produce very inexpensive detailed DNA sequence information for complex organisms' genomes will both lead to accelerated discoveries throughout biology and provide the basis for Pharmacogenomics, a new paradigm in therapeutics wherein medicines are prescribed based on individual genotypes rather than just observed symptoms.