Metabolomics: an accurate mass GC-DART AccuTOF mass spectrometer for routine iden

描述(由申请人提供)：我们正在为JEOL DART AcuTOF质谱仪系统申请资金，该系统包括一台Gerstel MPS2机器人自动进样器，带有用于GC分离的冷注入系统。美国国立卫生研究院资助的研究人员进行代谢组学分析，以便对人类和动物模型中遗传或疾病改变的代谢后果进行表型分析。戴维斯的这项研究由于缺乏结合了高质量精度和良好灵敏度和同位素准确度的气相色谱分离的仪器而受到影响。在加州大学戴维斯分校的代谢组学设施中，已对超过22,000个低分辨率GC-TOF MS色谱图进行了筛选，以确定1,000多种已识别的代谢物。数据被处理并存储在独特的BinBase数据库中，用于对迄今进行的345项研究的峰(包括未知化合物)进行比较。对于主要用户的项目，这些研究产生了重要数据，并出版了大量出版物。我们还发现了许多在病例/对照研究的比较中具有统计意义的化合物，我们需要一个好的注释方案来执行生化评估。这种注释的出发点是获得分子离子的准确质量数据。我们比较了我们发表的在(借出的)Waters GCTPremier中使用化学电离的软电离的结果，以及结合气相色谱分离和DART电离的替代JEOL accuTOF质谱仪。质量准确度是可以接受的，平均质量误差为3亩，但JEOL仪器中的同位素准确度比GCT总理女士所确定的更好。因此，我们相信JEOL GC-DART AcuTOF质谱仪将对这笔赠款的主要用户和加州大学戴维斯分校的更广泛的研究界产生重大影响。该仪器将放置在加州大学戴维斯分校基因组中心的代谢设施核心单元，有专门和训练有素的工作人员监督该仪器的操作、维护和管理。代谢组学机构成立于2005年，旨在与校园教师合作提供尖端研究和服务，特别是推进分析和信息学方法，研究涉及小分子的代谢失调。服务核心单位和研究单位之间的互动，以及将这些实验室合并为一个单一设施，使该设施所有工作人员使用的方法和工具得以定期改进。加州大学戴维斯分校基因组学中心代谢设施核心单元为两个校区(萨克拉门托和戴维斯)提供这些服务，这两个校区包括800多名生物学教师和4000多名研究生。

DESCRIPTION (provided by applicant): We are requesting funds for a Jeol DART accuTOF mass spectrometer system including a Gerstel MPS2 robotic autosampler with a cold injection system for GC separations. NIH funded investigators pursue metabolomic analyses in order to phenotype the metabolic consequences of genetic or disease alterations in humans and animal models. This research is compromised in Davis by the lack of instrumentation combining gas chromatographic separations with high mass accuracy and good sensitivity and isotope accuracy. In the Metabolomics Facility at UC Davis, over 22,000 low- resolution GC-TOF MS chromatograms have been screened for over 1,000 identified metabolites. Data were processed and stored in the unique BinBase database for comparison of peaks (including unknown compounds) across the 345 studies that were conducted so far. For the projects of the major users, these studies have yielded important data which led to a wide range of publications. We also found many compounds that were statistically significant in comparisons of case/control studies for which we need a good annotation scheme to perform biochemical assessments. The starting point for such annotations is to obtain accurate mass data for the molecular ions. We have compared our published results from soft ionization using chemical ionization in the (loaned) Waters GCTpremier to the alternative Jeol accuTOF mass spectrometer in conjunction with gas chromatography separation and DART ionization. Mass accuracy was acceptable with average mass errors of ¿3 mu, but isotope accuracy was even better in the Jeol instrument than determined by the GCTpremier MS. We are therefore convinced that the Jeol GC-DART accuTOF mass spectrometer will have a major impact on the major users of this grant and the greater UC Davis research community. The instrument will be placed in the Metabolomics Facility core unit of the UC Davis Genome Center, with dedicated and trained staff available to oversee the operation, maintenance and management of this instrument. The Metabolomics Facility has been established in 2005 to provide cutting-edge research and service in collaboration with campus faculty, specifically to advance analytical and informatics methods to study metabolic dysregulation involving small molecules. The interaction between service core unit and research unit and the integration of these laboratories to a single Facility enables a regular improvement of methods and tools used by all staff in the Facility. The UC Davis Genome Center Metabolomics Facility core unit provides these services to two campuses (Sacramento and Davis) which include over 800 biology faculty and more than 4,000 graduate students.