Single-stranded sequencing using microfluidic reactors (SISSOR)

使用微流体反应器（SISSOR）进行单链测序

• 批准号: 8753802
• 负责人: XIAOHUA HUANG
• 金额: $ 91.87万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8753802
• 关键词: Algorithms; Biotechnology; Cells; Chemistry; Chromosomes; Clinical; Communities; Complex; Computational algorithm; Consensus; DNA; DNA amplification; Data; Development; Device Designs; Devices; Dissociation; Engineering; Genetic; Genome; Genomics; Goals; Haplotypes; Human; Human Genome; Length; Libraries; Life; Malignant neoplasm of brain; Measures; Medical; Methods; Microfluidic Microchips; Microfluidics; Nature; Nucleotides; Organism; Peer Review; Performance; Phase; Preparation; Publications; Reading; Research; Single-Stranded DNA; Somatic Mutation; Synthesis Chemistry; Technology; Tissues; Touch sensation; Validation; Variant; base; clinical application; commercialization; cost; design; genome sequencing; improved; prototype; public health relevance; reconstruction; success

DESCRIPTION (provided by applicant): Recent advances in acquiring genome information quickly and inexpensively have transformed many aspects of biomedical and environmental research. Clinical sequencing applications have emerged, and are at the beginning of touching our daily life. While the previously thought unreachable goal of $1,000 genome has become a difficult-to-miss target within the next 2-3 years, major challenges still remain in terms of both accuracy and long-range continuity, both have direct implications in the clinical applicability of genome sequencing as well as many non- medical applications. In this project we will develop SISSOR (SIngle-Stranded Sequencing using micrOfluidic Reactors), with the goal of sequencing a mammalian-size genome at the consensus error rate of 10-9 or lower, with a haplotype contig N50 of at least 10 Mb for $1,000. In addition, SISSOR can start with one single cell, providing the capability of dissecting somatic mutations in heterogeneous tissues (such as cancers and brain), and extracting genome information de novo from difficult-to-culture organisms. Instead of proposing a completely new sequencing method, we chose to develop an integrative device focusing on the front-end preparation, which, in combination with the existing sequencing-by-synthesis chemistry, provides a highly realistic path to achieve the above goal within a 4-year development cycle.

描述（由申请人提供）：快速，廉价地获取基因组信息的最新进展改变了生物医学和环境研究的许多方面。临床测序应用已经出现，并且正处于接触我们的日常生活的开始。尽管以前认为的1,000美元基因组的无法实现的目标已在未来2 - 3年内成为难以置信的目标，但在准确性和远程连续性方面仍然存在主要挑战，两者都对基因组测序的临床适用性以及许多非医学应用都有直接影响。在这个项目中，我们将开发触犯（使用微流体反应器进行单链测序），其目的是以10-9或更低的共识错误率进行测序，并以至少10 MB的单倍型内型N50的共识错误率为1,000美元。此外，Sissor可以从一个单个细胞开始，从而提供了在异质组织（例如癌症和大脑）中剖析体细胞突变的能力，并从难以培养的生物体中从头提取基因组信息。我们没有提出一种全新的测序方法，而是选择开发着一个集中在前端制备上的集成装置，该设备与现有的逐一测序化学结合使用，为在4年开发周期内实现上述目标提供了高度现实的途径。