An in vitro method for generating long-range read pair data for genomic assembly and analysis.

一种生成用于基因组组装和分析的远程读取对数据的体外方法。

• 批准号: 8981032
• 负责人: Nicholas Helms Putnam
• 金额: $ 73.69万
• 依托单位: DOVETAIL GENOMICS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8981032
• 关键词: Algorithms; Area; Basic Science; Biological Assay; Cells; Clinic; Clinical; Clinical Research; Code; Communities; Computer software; Computing Methodologies; DNA; DNA Sequence; Data; Detection; Development; Diagnosis; Dideoxy Chain Termination DNA Sequencing; Disease; Gene Expression Regulation; Generations; Genome; Genomics; Goals; Haplotypes; Health; Human; Human Genome; In Vitro; Individual; Inheritance Patterns; Knowledge; Libraries; Link; Malignant Neoplasms; Marketing; Medical; Metagenomics; Methods; Mus; Organism; Partner in relationship; Patients; Phase; Population; Price; Process; Production; Reading; Research; Research Infrastructure; Services; Source; Speed; Technology; Time; Tissues; Validation; Variant; Work; base; cloud based; cohort; commercial application; cost; cost effective; falls; genetic variant; genome sequencing; human disease; improved; instrument; next generation; next generation sequencing; novel; personalized medicine; prototype; public health relevance; research and development; scaffold; vertebrate genome; web services

 DESCRIPTION (provided by applicant): The production of whole genome sequences (de novo assembly) is fundamental to both basic and clinical genomics research in the areas of gene regulation, structural variant detection, haplotype phasing, and metagenomics analysis. The 10,000 fold reduction in raw Next Generation DNA Sequencing (NGS) costs the past seven years has made genomics research much more affordable. However, while economical these technologies currently produce highly fragmented genome assemblies. Dovetail Genomics has developed a novel and cost-effective Multi-Scale Linking (MSL) sequencing library that leverages existing NGS technology to improve the median assembly size (N50) over 100 fold from less than 100 kbp to greater than 10 Mbp. Our service will utilize these libraries and our novel assembly algorithms to produce high quality, more complete genomes beginning from only DNA, no cells or tissue required. Furthermore, we will do so rapidly (less than one month) and economically (less than $30,000). Our service can also be used to improve existing assemblies for less than $10,000. A principal feature of these libraries that enables such improvement is the production of genomic read pairs spanning many scales and extremely long distances. Our software pipeline leverages this feature to produce more contiguous and complete genome assemblies. Our long-term goal with the provision of these high-quality genomes is the improvement of human health and the expansion of human knowledge of ourselves and other organisms. Higher quality genomes enable more powerful studies and understanding of human genomic disease. They also place personalized medicine within reach via the rapid and affordable provision of individual patient genomes. In Dovetail's first year we demonstrated the feasibility of our technologies' capability to increase genome assembly contiguity 100 fold. Moving forward we are striving to refine both our library production and analysis platforms to a commercially viable level. This will require increasing the value of the data produced by our proprietary sequencing libraries and refining and deploying our assembly pipeline and other analysis software. Our specific aims to accomplish this feat are: (1) Increase the efficiency and genomic range of our library production platform. (2) Improve our existing prototype assembly pipeline, optimizing speed and scalability by transitioning to cloud-based compute infrastructure. (3) Improve existing pipelines for genomic phasing and the detection and characterization of structural variation in humans for clinical genomics. There are commercial opportunities for such a service in both academic and clinical research, as well as in the clinic itself. Sufficiently complete and cost-effective genome assemblies will enable broader and more powerful studies of genomes at both the population and individual level. In clinical research, where large patient cohorts are the norm, they will enable the discovery and description of genomic drivers of human disease. And in the clinic itself they will enable the rapid acquisition of patient genomes for diagnosis and treatment of many diseases, including and especially cancer.

 描述(由申请人提供)：全基因组序列(从头组装)的产生是基础和临床基因组学研究的基础，在基因调控、结构变异检测、单倍型分期和元基因组分析领域。在过去的七年里，下一代DNA测序(NGS)的原始成本降低了10,000倍，这使得基因组学研究变得更加负担得起。然而，这些技术虽然经济，但目前产生了高度碎片化的基因组组合。燕尾基因组公司开发了一种新颖且具有成本效益的多尺度链接(MSL)测序文库，该文库利用现有的NGS技术，将组装尺寸(N50)的中位数提高了100倍以上，从不到100 KBP提高到10 MBP以上。我们的服务将利用这些文库和我们的新组装算法来生产高质量、更完整的基因组，只需从DNA开始，不需要细胞或组织。此外，我们将迅速(不到一个月)和经济(不到30,000美元)这样做。我们的服务也可以用来改进现有的组装，花费不到10,000美元。这些文库的一个主要特征是能够产生跨越许多规模和极长距离的基因组阅读对。我们的软件流水线利用这一功能来生产更连续和完整的基因组组件。我们提供这些高质量基因组的长期目标是改善人类健康，扩大人类对自身和其他生物体的了解。更高质量的基因组使人们能够更有力地研究和了解人类基因组疾病。他们还通过快速和负担得起的个体患者基因组提供，使个性化医疗变得触手可及。在Dovetail的第一年，我们证明了我们的技术将基因组组装邻接性提高100倍的可行性。展望未来，我们正在努力完善我们的图书馆生产和分析平台，使其达到商业上可行的水平。这将需要增加我们专有测序库产生的数据的价值，并改进和部署我们的组装管道和其他分析软件。我们实现这一壮举的具体目标是：(1)提高我们文库生产平台的效率和基因组范围。(2)改进我们现有的原型组装流水线，通过过渡到基于云的计算基础设施来优化速度和可扩展性。(3)改进现有的用于基因组分期和临床基因组学检测和表征人类结构变异的管道。这种服务在学术和临床研究以及诊所本身都有商业机会。足够完整和具有成本效益的基因组组合将能够在群体和个体层面上对基因组进行更广泛和更强大的研究。在临床研究中，大规模患者队列是常态，它们将使发现和描述人类疾病的基因组驱动因素成为可能。在临床上，它们将使快速获取患者基因组用于诊断和治疗许多疾病，包括尤其是癌症。