CAREER: Open-Access, Real-Time High-Throughput Metabolomics for High-Field and Benchtop NMR for Biological Inquiry

代谢组学是系统生物学中不可或缺的一种方法，它使用分析技术来测量细胞、组织和生物液中的代谢物，并提供生物表型的直接信息。核磁共振波谱是代谢组学研究的有力工具，因为它具有良好的分析重复性和一次检测大量代谢物的能力。核磁共振代谢组学通常是在高场(HF)光谱仪上进行的，但最近台式光谱仪的发展重新引起了人们对低场(LF)核磁共振的兴趣，因为与HF相比，它的可访问性、低成本和占用空间小。然而，高频和台式低频的核磁共振代谢组学需要耗时的、依赖于用户的处理和代谢物识别和定量的专业知识。由于这些限制，高频和低频核磁共振在生物界的代谢组学研究中都没有得到充分的探索。该项目将通过开发、验证和传播用于高频和台式低频核磁共振的实时、高通量核磁共振代谢技术来填补这些关键空白，以推进生物基础设施和研究。这一跨学科项目将为下一代妇女和少数族裔从事生物工程和生物信息学职业做好准备--目前这是一门代表性不足的学科。该项目还将把研究与教育目标结合起来，以更广泛的社区，从K-12到研究生和普通公众：(A)课程工作，以加强本科和研究生课程中的生物信号处理和分析技能；(B)针对有才华的女性、少数族裔和低收入大学生的实习；(C)实践STEM项目，通过与学校教师合作，激励高中生；(D)传播生物工程研究，通过女性工程师协会、West TN STEM Hub和女孩体验工程方案支持K-12学习；以及(E)在当地博物馆展出教育展品，使公众能够接触到核磁共振应用。这种早期的实践接触将有利于所有年龄段的学生理解基本概念并实现核磁共振在广泛领域的应用-包括分子生物学、生物医学工程和化学工程-并最终激励他们追求STEM职业生涯。该项目将开发、验证和传播开放获取的代谢组学技术，这些技术将通过以下目标自动量化从高场(HF)和台式低场(LF)核磁共振获得的复杂生物光谱中的代谢物：1)使用深度学习研究高频核磁共振的高通量代谢组学方法，2)使用自动编码器从台式低场核磁共振重建高分辨率和高通量谱，3)研究这些用于查询生物学问题的技术，以及4)通过开放获取软件传播代谢组库和用于生物研究和教育的技术。这项研究将在核磁共振代谢组学领域取得突破，消除高频和台式核磁共振的主要处理障碍，从而使核磁共振成为生物界可获得的有效分析工具。该项目的结果将在机构网站上公布：https://www.memphis.edu/mrisl/projects/index.phpThis奖反映了国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Metabolomics is an indispensable approach in systems biology that uses analytical techniques to measure metabolites in cells, tissues, and biofluids and provides direct information of the biological phenotype. Nuclear magnetic resonance spectroscopy (NMR) is a powerful tool for metabolomics due to its excellent analytical reproducibility and ability to detect numerous metabolites in a single measurement. NMR metabolomics is conventionally performed on a high-field (HF) spectrometer, but the recent development of benchtop spectrometers has led to a resurgence of interest in low-field (LF) NMR due to its accessibility, low cost and small footprint compared to HF. NMR metabolomics at both HF and benchtop LF, however, require time-consuming, user-dependent processing and expertise for metabolite identification and quantification. Due to these limitations, both HF and LF NMR are underexplored for metabolomics research in the biological community. This project will fill these critical gaps by developing, validating, and disseminating real-time, high-throughput NMR metabolomic techniques for both HF and benchtop LF NMR for advancing biological infrastructure and research. This interdisciplinary project will prepare the next generation of women and minorities to pursue bioengineering and bioinformatics career—currently an under-represented discipline. The project will also integrate research with educational objectives to target the broader community from K–12 to graduate students and the general public: (a) coursework to strengthen biosignal processing & analysis skills in undergraduate and graduate curricula; (b) internships, targeted to talented women, minority, and low-income college students; (c) hands-on STEM projects to motivate high-schoolers through collaboration with school teachers; (d) disseminate bioengineering research to support K–12 learning through the Society of Women Engineers, West TN STEM Hub, and Girls Experiencing Engineering programs; and (e) educational exhibits at local museums to enable public outreach and exposure to NMR applications. This early hands-on exposure will benefit students of all ages to understand fundamental concepts and realize NMR applications in a broad range of fields—including molecular biology, biomedical engineering and chemical engineering—and ultimately motivate them to pursue a STEM career. The project will develop, validate, and disseminate open-access metabolomic techniques that will automatically quantify the metabolites in complex biological spectra obtained from high-field (HF) and benchtop low-field (LF) NMR via the following objectives: 1) investigate high-throughput metabolomic methods for HF NMR using deep learning, 2) reconstruct high-resolution and high-throughput spectra from benchtop LF NMR using autoencoder, 3) investigate these techniques for inquiring biological questions, and 4) disseminate metabolomic libraries and techniques for biological research and education via an open-access software. This research will provide a breakthrough in the field of NMR metabolomics by eliminating a major processing barrier for both HF and benchtop NMR, thus making NMR an accessible and effective analytical tool to the biological community. The results of this project will be available at the institutional website: https://www.memphis.edu/mrisl/projects/index.phpThis 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.