A Web-Based Data Source for Metabolomics Analysis

凯斯西储大学获得了一笔奖金，用于建造促进新陈代谢研究的计算工具。代谢物是作为中间产物和代谢产物的分子。目前，该国大多数医院和卫生保健中心的血液实验室只能在血液样本中测量少量(不到15种)代谢物。然而，最近高能物理技术的进步使(目前的研究人员)有可能测量血液样本中更大数量的代谢物，最多可达300个。当这些测量结果与健康人(即对照受试者)的测量结果不同时，基本的问题是：它们意味着什么？目前，上述问题只能由代谢生物化学专家手动回答。这个项目将测试通过计算和算法推导出的对如此大的代谢物测量集合的第一次切割解释的有效性。这些解释是通过基于网络的、数据库启用的、易于使用的、在线的和可靠的正确的软件系统来实现的，这些软件系统可扩展到整个代谢网络，而不是其中的一部分，并以众所周知和公认的代谢生物化学原理为基础，而不是手动完成，因为周围没有足够的代谢生物化学专家来手动解释每个这样的实验室结果。该项目开发了一个基于网络的资源及其工具，以使研究界能够帮助回答上述问题。该资源的工具包括-观察代谢物分析工具，该工具消除那些不可能引起观察到的测量的代谢路径(即，代谢网络中的非活跃代谢路径)，并提供可能引起观察到的测量的激活代谢路径的小列表。注意，没有做出任何努力来返回网络中的实际流量估计，从而简化了手头的任务；-面向代谢组学的查询工具，其允许研究人员/用户进一步关注子网络内的激活代谢路径(通过允许他们制定关于激活路径、无效周期等的查询)，并向用户提供其查询答案的解释；-面向代谢组学的可视化工具，其提供完整代谢网络内的激活路径或网络的放大和聚焦部分的可视化，允许用户可视地解释和分析结果。由此产生的在线工具将是用于对学生进行代谢生物化学教育的优秀的基于网络的教育工具，生物学、生物信息学和代谢组学--培训他们在代谢网络模型方面使用生物信息学工具。有关该项目的更多信息，请访问http://nashua.case.edu/.。

"This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."Case Western Reserve University has been awarded a grant to build computational tools to facilitate research in metabolic profiles. Metabolites are molecules that are intermediates and products of metabolism. Current blood-labs in most hospitals and health care centers in the country can only measure in a blood sample small numbers of (less than 15) metabolites. However, recent advances in high-energy physics technologies has now made it possible (for researchers for the time being) to measure much larger numbers of metabolites in a blood sample, up to about 300 of them. When these measurements differ from those in a healthy individual (i.e., the control subject), the basic question is: what do they mean? Currently, the above question can only be answered manually by experts in metabolic biochemistry. This project will test the validity of computationally and algorithmically deduced first-cut interpretations of such large sets of metabolite measurements. These interpretations are made available through web-based, database-enabled, easy-to-use, online and reliably correct software systems that are - Scalable to the complete metabolic network, not parts of it and - Grounded by the well-known and accepted metabolic biochemistry principles,instead of being done manually as there are not enough metabolic biochemistry experts around to manually interpret each such lab result. This project develops a web-based resource and its tools to enable the research community to help answer the above-listed question. The tools of the resource include - Observed Metabolite Analysis tool that eliminates those metabolic paths that cannot have caused the observed measurements (i.e., inactive metabolic paths in the metabolic network), and provides a small list of activated metabolic paths that may have caused the observed measurements. Note that no effort is made to return actual flux estimations in the network, simplifying the task at hand, - Metabolomics-Oriented Querying tool, that allows researchers/users to further focus on activated metabolic paths within a subnetwork (by allowing them to formulate queries about activated paths, futile cycles, etc.), and provides users with explanations of its query answers, - Metabolomics-Oriented Visualization tool, which provides visualizations of activated paths within the complete metabolic network or zoomed-in and focused parts of the network, allowing users to visually interpret and analyze the results.The resulting online tools will be an excellent web-based educational tool for educating students in metabolic biochemistry, biology, bioinformatics, and metabolomics--to train them on the use of bioinformatics tools in terms of metabolic network models. Additional information about the project may be found at http://nashua.case.edu/.