Experimental Core

实验核心

基本信息

批准号：
10213204
负责人：
RICHARD D SMITH
金额：
$ 50.49万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10213204
关键词：
Adoption Algorithms Biological CD69 antigen Chemical Exposure Chemicals Chemistry Communities Complex Mixtures Computer Models Data Databases Development Educational workshop Elements Equipment and supply inventories Funding Gases Ions Isomerism Isotopes Laboratories Mass Spectrum Analysis Measurement Measures Methodology Methods Molecular Molecular Probes Molecular Structure Pacific Northwest Phase Plasma Probability Procedures Property Protocols documentation Reference Standards Reproducibility Research Personnel Resolution Resource Sharing Sampling Shapes Source Stable Isotope Labeling Structure Techniques Technology Transcend United States National Institutes of Health Urine Validation Work algorithm training base chemical property computerized tools data dissemination data mining data standards experience flexibility improved in silico innovation instrument instrumentation ion mobility mass spectrometer metabolome metabolomics microbial next generation novel programs success tandem mass spectrometry ultra high resolution

项目摘要

EXPERIMENTAL CORE SUMMARY More than 99% of known metabolites and chemicals cannot be identified in metabolomics studies because no reference materials or data exist for them. Therefore, a large number of metabolites remain unidentified, while a limited number of metabolites are identified repeatedly. The inclusion of many features that probe the molecular structure of metabolites, which can be consistently measured experimentally and accurately predicted computationally, is crucial for the success of any compound identification approach that transcends the paradigmatic-use of reference standards. We plan to utilize ion mobility-mass spectrometry (IM-MS), with tandem mass spectrometry (MS/MS), to provide quantitative measures of the shape and chemistry of molecules to characterize and identify molecules that otherwise are indistinguishable by current approaches. The Experimental Core will facilitate a transition past the need for reference standards by providing experimental validation of predicted molecular properties and computational models, experimental validation of a multi- property compound identification algorithm, and dissemination of data and SOPs for best utilization of experimental measurements and calculated molecular properties. This work is significant because it, in concert with a complementary Computational Core, supports the development of a new, paradigm-shifting metabolomics analytical methodology that greatly expands the number of biologically relevant compounds that can be quickly identified in metabolomics studies. This work is innovative because it implements accurate and reproducible measurement of multiple molecular properties, employs flexible measurement platforms and readily transferable protocols, and provides an next-generation IM-MS analysis platform.

实验核心总结超过 99% 的已知代谢物和化学物质无法在代谢组学研究中鉴定，因为没有参考文献他们存在材料或数据。因此，大量的代谢物仍未被鉴定，而有限数量的代谢物代谢物被反复鉴定。包含许多探测代谢物分子结构的特征，可以通过实验一致测量并通过计算准确预测，对于成功至关重要任何超越参考标准范式使用的化合物鉴定方法。我们计划利用离子淌度质谱 (IM-MS) 与串联质谱 (MS/MS) 相结合，可提供分子的形状和化学性质，用于表征和识别电流无法区分的分子接近。实验核心将通过提供参考标准来促进过渡预测分子特性和计算模型的实验验证，多因素的实验验证属性化合物识别算法，以及数据和 SOP 的传播，以实现实验的最佳利用测量和计算的分子特性。这项工作意义重大，因为它与互补的计算核心支持开发一种新的、范式转变的代谢组学分析方法，极大地扩展了可以在代谢组学研究中快速鉴定的生物学相关化合物的数量。这这项工作具有创新性，因为它实现了多种分子特性的精确且可重复的测量，采用灵活的测量平台和易于转移的协议，并提供下一代 IM-MS 分析平台。