Ordered Arrays for Advanced Sequencing Systems

描述(申请人提供)：项目摘要/摘要：虽然人类基因组序列在几年前已基本完成，但对DNA序列数据的生产仍有巨大的需求。可进行测序的生物体和个体的数量仍然受到当今桑格测序方法耗时长、复杂性高和成本过高的显著限制。目前正在进行一项重大努力，以创造新的化学方法，在不使用电泳的情况下读出DNA链的碱基；然而，为这些测序系统提供支持的样品准备过程尚未完全制定和优化。许多先进的测序方法需要数百万组扩增的DNA片段，每组都由数百万个相同的片段组成。这些组被连接到固体载体上，然后进行处理以读出序列；然而，在玻璃载体上产生DNA模板阵列目前需要一组复杂的步骤。在第一阶段，我们将研究以有序格式产生样本阵列与以随机格式产生样本阵列的好处，并将产生高密度有序阵列的原型。第一阶段里程碑的成功完成以及随后的第二阶段和第三阶段项目的完成将导致开发一种超高通量原型系统，该系统可以生产成本效益高的高密度芯片，与先进的DNA测序仪器一起使用。最终，这种下一代样本准备和测序技术可以比现有系统更便宜、更快地产生几个数量级的DNA序列，有助于使个性化药物的承诺成为现实。项目简介：最终，为复杂生物的基因组产生非常廉价的详细DNA序列信息的能力将导致整个生物学的加速发现，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，其中药物是根据个体基因类型而不是仅仅观察到的症状来开出的。一种可以廉价地对特定肿瘤内的DNA进行测序的系统将有助于癌症研究人员了解与各种类型癌症相关的突变，并有助于导致更有效的治疗。由于一个人的基因组序列永远不会改变，未来很可能每个人都会在出生时对他们的基因组进行测序，以电子方式记录下来，并在一生中用于定制他们的医疗保健。

DESCRIPTION (provided by applicant): Project Summary/Abstract: Although the sequence of the human genome was substantially completed a few years ago, there is still a huge need for the production of DNA sequence data. The number of organisms and individuals which may be sequenced is still significantly constrained by the lengthy time, high complexity and exorbitant costs of today's Sanger sequencing methods. A Significant effort is currently going into the creation of new chemistries to read out the bases of DNA strands without the use of electrophoresis; however, the sample preparation processes to feed these sequencing systems has yet to be fully worked out and optimized. Many of the advanced sequencing methods require many millions of sets of amplified DNA fragments, with each set being comprised of millions of identical fragments. These sets are attached to a solid support which is then processed to read out the sequence; however, the generation of the array of DNA templates on a glass support currently requires a complex set of steps. In Phase I, we will examine the benefits of producing arrays of samples in an ordered format versus a random one and will produce prototype high-density ordered arrays. Successful accomplishment of the Phase I milestones and completion of subsequent Phase II and Phase III projects will result in the development of an ultra-high throughput prototype system which can produce cost-effective high-density chips for use in conjunction with advanced DNA sequencing instruments. Ultimately, this next generation of sample preparation and sequencing technologies, which can produce DNA sequence several orders of magnitude cheaper and faster than existing systems, can help to make the promise of personalized medicine a reality. Project Narrative: 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. A system which could inexpensively sequence the DNA within a specific tumor will help cancer researchers understand the mutations associated with various types of cancers and help lead to more effective treatments. Since one's genomic sequence never changes, it is likely in the future that everyone will have their genomes sequenced at birth, recorded electronically and used throughout their lifetime to customize their healthcare.