Streamlined Template Preparation for Advanced Sequencing Methods

简化高级测序方法的模板准备

• 批准号: 7159545
• 负责人: Steven Jeffrey Gordon
• 金额: $ 16.11万
• 依托单位: INTELLIGENT BIO-SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-09 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7159545
• 关键词: DNA; gene mutation; genome; neoplasm /cancer; nucleic acid sequence; reading

DESCRIPTION (provided by applicant): Project Summary/Abstract: Although the sequence of the human genome was substantially completed in 2002, there is still a huge need for the production of DNA sequence data. In particular, the genome within carcinogenic tissues is believed to vary widely from a normal genome, both in inherited mutations and those caused by the disease. The NCI has recently set a goal of sequencing 12,500 genomes from malignant tumors of different individuals in order to learn more about the molecular basis of the disease. To cost effectively reach this goal, new technologies for DNA sequencing will be required. We propose to use the sequencing by synthesis (SBS) method as the basis for a prototype instrument which will be capable of effectively sequencing genomes from highly mutated tumor tissues. When fully optimized, our system should be able to produce read lengths which are at least as long as today's state-of-the-art electrophoresis-based systems. This may become a critical parameter for cancer genomes which have undergone sufficiently complex mutations that will make accurate assembly of short re- sequencing data difficult. In this Phase I SBIR project, we propose to develop the sample preparation approach which will simplify the SBS steps and make the process more robust for long sample reads and could be implemented on hundreds of thousands or millions of samples. Successful accomplishment of the Phase I milestones and completion of a subsequent Phase II and Phase III projects will result in the development of an ultra-high throughput 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 give researchers more insight into the molecular mechanisms of cancer and make the promise of individualized treatments 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 throughput their lifetime to customize their healthcare.

描述(申请人提供)：项目摘要/摘要：虽然人类基因组的测序工作已于2002年基本完成，但对DNA测序数据的生产仍有巨大的需求。特别是，致癌组织中的基因组被认为与正常基因组有很大的不同，无论是遗传突变还是由疾病引起的突变。NCI最近制定了一个目标，对不同个体的恶性肿瘤的12,500个基因组进行测序，以了解更多关于这种疾病的分子基础。为了经济高效地实现这一目标，将需要新的DNA测序技术。我们建议使用合成测序(SBS)方法作为原型仪器的基础，该仪器将能够有效地对高度突变的肿瘤组织的基因组进行测序。当完全优化时，我们的系统应该能够产生至少与当今最先进的基于电泳的系统一样长的读数长度。这可能成为癌症基因组的一个关键参数，因为癌症基因组已经经历了足够复杂的突变，这将使准确组装短的重新测序数据变得困难。在这个第一阶段的SBIR项目中，我们建议开发一种样品制备方法，这种方法将简化SBS步骤，使这一过程更适用于长时间的样品读取，并可以对数十万或数百万个样品实施。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，这种新一代的样本制备和测序技术可以产生比现有系统便宜几个数量级、速度更快的DNA序列，可以帮助研究人员更深入地了解癌症的分子机制，并使个性化治疗的承诺成为现实。项目简介：最终，为复杂生物体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，很可能在未来，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，并使用一生的吞吐量来定制他们的医疗保健。