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

 描述（由申请人提供）：全基因组序列的产生（从头组装）是基因调控、结构变异检测、单倍型定相和宏基因组学分析领域的基础和临床基因组学研究的基础。在过去的七年中，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实惠。然而，尽管经济，这些技术目前产生高度片段化的基因组组装体。Dovetail Genomics开发了一种新型且具有成本效益的多尺度连接（MSL）测序文库，该文库利用现有的NGS技术将中值组装大小（N50）从小于100 kbp提高到大于10 Mbp。我们的服务将利用这些文库和我们的新型组装算法来生产高质量，更完整的基因组，仅从DNA开始，不需要细胞或组织。此外，我们将迅速（不到一个月）和经济地（不到30 000美元）这样做。我们的服务还可以用于改进现有的组件，成本不到10，000美元。能够实现这种改进的这些文库的主要特征是跨越许多尺度和极长距离的基因组读段对的产生。我们的软件管道利用这一功能来生产更连续和完整的基因组组装。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。更高质量的基因组能够更有力地研究和理解人类基因组疾病。他们还通过快速和负担得起的提供个体患者基因组，使个性化医疗触手可及。在Dovetail的第一年，我们证明了我们的技术能够将基因组组装的连续性提高100倍。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，以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)改进现有的基因组定相管道，以及临床基因组学中人体结构变异的检测和表征。这种服务在学术和临床研究以及诊所本身都有商业机会。充分完整和具有成本效益的基因组组装将使更广泛和更强大的基因组研究在人口和个人水平。在临床研究中，大型患者队列是常态，它们将有助于发现和描述人类疾病的基因组驱动因素。在临床上，它们将能够快速获取患者基因组，用于诊断和治疗许多疾病，特别是癌症。

 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.