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方法，它使用分析技术来测量细胞、组织和生物流体中的代谢物，并提供生物表型的直接信息。核磁共振波谱（NMR）是代谢组学的强大工具，因为它具有出色的分析再现性和在一次测量中检测多种代谢物的能力。核磁共振代谢组学传统上是在高场（HF）光谱仪上进行的，但最近台式光谱仪的发展导致了对低场（LF）核磁共振的兴趣的复苏，因为它与HF相比具有可访问性，低成本和小占地面积。然而，在HF和台式LF上进行核磁共振代谢组学都需要耗时、依赖用户的处理和代谢物鉴定和量化的专业知识。由于这些限制，HF和LF NMR在生物群落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HF和台式LF NMR的实时、高通量NMR代谢组学技术来填补这些关键空白，以推进生物基础设施和研究。这个跨学科的项目将为下一代女性和少数民族从事生物工程和生物信息学的职业做准备-目前这是一个代表性不足的学科。该项目还将把研究与教育目标结合起来，面向从K-12到研究生和普通大众的更广泛群体：(a)在本科和研究生课程中开设课程，加强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)通过与学校教师合作，开展STEM实践项目，激励高中生；(d)通过女性工程师协会、西田纳西州STEM中心和女孩体验工程项目传播生物工程研究，以支持K-12学习；(e)在当地博物馆举办教育展览，使公众能够接触到核磁共振应用。这种早期的动手接触将有利于所有年龄段的学生了解基本概念，并在广泛的领域实现核磁共振应用，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。该项目将开发、验证和推广开放获取的代谢组学技术，该技术将自动量化从高场（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，目标如下：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)使用自动编码器重建台式低低频核磁共振的高分辨率和高通量光谱，3)研究这些技术用于查询生物学问题，4)通过开放获取软件传播代谢组学库和技术，用于生物学研究和教育。该研究将通过消除高频和台式核磁共振的主要处理障碍，为核磁共振代谢组学领域提供突破，从而使核磁共振成为生物界可访问和有效的分析工具。该项目的结果将在该机构的网站上公布：https://www.memphis.edu/mrisl/projects/index.phpThis该奖项反映了美国国家科学基金会的法定使命，并通过基金会的智力价值和更广泛的影响审查标准进行评估，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.