SBIR Phase II: Development of a Novel Measurement Technology to Enable Longitudinal Multiomic Investigations of the Gut Microbiome

这个小企业创新研究（SBIR）第二阶段项目的更广泛影响将是通过对微生物RNA进行大规模，密集的纵向测量和分析，显着增加微生物组领域的商业，科学和人类健康潜力。这可以使：（1）由于缺乏可重复数据而导致的错误发现显著减少;（2）成本大幅降低-确保整个行业都能获得这些进步;（3）高频采样，使时间序列探索成为常规;以及（4）创建包含DNA和RNA数据的大规模数据库，这可能导致前所未有的发现和验证精确医学生物标志物。该项目的成功完成很有可能促进美国公众的健康和福利，提高美国医疗保健和生命科学部门的经济竞争力，该拟议项目描述了现有微生物组测量和分析平台的RNA功能的开发，该平台由自动化样品收集系统和序列数据的分析引擎。目前，肠道微生物表达哪些基因的问题（可以使用RNA转录本进行研究）是一个非常有前途的研究领域，可以促进对宿主-微生物相互作用的理解。这是因为构成少量肠道微生物组的细菌仍然可以通过它们的基因表达显著影响社区。DNA序列数据可以忽略这一点，因为它只测量细菌丰度。尽管如此，RNA仍然没有得到充分利用，因为RNA在细胞外迅速降解，并且大多数实验室缺乏以任何显著规模可靠地测量RNA的能力。该项目的主要活动将是（1）完善RNA捕获和存储的过程，（2）将其集成到自动化硬件系统中，以及（3）开发用于分析所得RNA数据集的方法和基础设施。该项目将使肠道微生物组中基因表达的研究变得普遍，使研究人员能够发现更强大的临床相关生物标志物，用于精准医学应用。该奖项反映了NSF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 II project would be a significant increase the commercial, scientific, and human health potential of the microbiome field by enabling large-scale, dense longitudinal measurement and analysis of microbial RNA. This could enable: (1) a significant reduction in false discoveries caused by a lack of reproducible data; (2) a major cost reduction – ensuring these advancements are accessible to the entire industry; (3) high-frequency sampling, making time-series explorations routine; and (4) the creation of a large-scale database that contains both DNA and RNA data, which could lead to unprecedented discovery and validation of precision medicine biomarkers. Successful completion of this project could have a high likelihood of advancing the health and welfare of the American public, increasing the economic competitiveness of the United States healthcare and life sciences sector, and enhancing partnerships between academia and industry.The proposed project describes the development of an RNA feature to an existing microbiome measurement and analysis platform that consists of an automated sample collection system and an analytics engine for sequence data. Currently, the question of which genes are being expressed by gut microbes (which can be studied using RNA transcripts) is an extraordinarily promising research field for advancing the understanding of host-microbial interactions. This is because bacteria that make up a small amount of the gut microbiome can still influence the community dramatically through their gene expression. This can be overlooked by DNA sequence data, which only measures bacterial abundance. Despite this, RNA remains under-utilized, as RNA quickly degrades outside of the cell, and most laboratories lack the capability to measure RNA at any significant scale reliably. The main activities of this project will be (1) refining a process for RNA capture and storage, (2) integrating these into the automated hardware system, and (3) developing the methods and infrastructure for analysis of the resulting RNA datasets. This project will allow studies of gene expression in the gut microbiome to become commonplace, allowing researchers to discover more powerful clinically relevant biomarkers for precision medicine applications.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.