SBIR Phase I: Low-Cost and Scalable Creation of Genomic Databases with Long-Read Next-Generation Sequencing

这项小企业创新研究（SBIR）第一阶段项目的更广泛影响将是开发和验证一种新方法，以促进人口水平获取目前无法获取的人类基因组中包含的遗传信息。重要的是，它可以大大减少扫描患有特定疾病的患者基因组所需的时间和成本，从几年到几个月，加快发现周期，并产生更高分辨率的数据，以开发更好的诊断工具或治疗方法。拟议的项目描述了一种高分辨率人类基因组测序的新方法，该方法使用独特的计算算法，促进使用泛基因组学方法检测不同类型的遗传变异，直接在原始测序数据上实现。短读下一代测序不能充分捕获的遗传变异，如大的染色体重排，长串联重复，或远程单倍型配置，代表了知识上的重大空白。在过去的几年里，成熟的长读次世代测序（NGS）技术已经开始揭示结构变异（SVs）和单倍型在疾病中的作用。然而，扩展长读NGS实现的主要限制是产生足够的测序覆盖以补偿相对较高的自然错误率的成本。所提出的技术可以直接解决这一问题，并促进经济高效的大规模人类基因组长读测序。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact of this Small Business Innovation Research (SBIR) Phase I project will be the development and validation of a new approach to facilitate population-level access to genetic information contained in the human genome currently inaccessible. Importantly, it can drive a significant reduction in time and cost needed to scan the genome of patients who suffer from a specific disease, from years to months, accelerating discovery cycles and producing data with higher resolution to develop better diagnostic tools or treatments. The proposed project describes a novel approach for high-resolution human genome sequencing using unique computational algorithms that facilitate detection of diverse types of genetic variation using a pangenomics approach, implemented directly on raw sequencing data. Genetic variation inadequately captured by short-read Next Generation Sequencing, such as large chromosomal rearrangements, long tandem repeats, or long-range haplotype configurations, represent a significant gap in knowledge. In the last few years, maturation of long-read Next Generation Sequencing (NGS) technologies have begun uncovering the role of Structural Variants (SVs) and haplotypes in disease. However, the main limitation to expand implementation of long-read NGS is the cost of generating sufficient sequencing coverage to compensate for the relatively high natural error rate. The proposed technology can address this issue directly and facilitate cost-effective long-read sequencing of human genomes at scale.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.