A Web-Based Data Source for Metabolomics Analysis

“该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。凯斯西储大学已获得一笔赠款，用于建立计算工具，以促进代谢谱的研究。代谢产物是代谢的中间体和产物。目前，该国大多数医院和医疗保健中心的血液实验室只能测量血液样本中的少量（少于15种）代谢物。然而，高能物理技术的最新进展现在使研究人员能够测量血液样本中大量的代谢物，多达300种。当这些测量结果与健康个体中的测量结果不同时（即，控制主体），基本问题是：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。这个项目将测试的有效性计算和算法推导出的第一次切割解释这样大的代谢物测量集。这些解释通过基于网络的、数据库支持的、易于使用的、在线的和可靠正确的软件系统提供，这些软件系统是-可扩展到完整的代谢网络，而不是其部分，并且-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，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，该工具消除了那些不能引起观察测量的代谢路径（即，代谢网络中的非活性代谢路径），并提供了可能导致观察到的测量结果的活性代谢路径的小列表。- 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、无效循环等的查询），并为用户提供查询答案的解释，-代谢组学导向的可视化工具，它提供完整代谢网络内的激活路径的可视化或网络的放大和聚焦部分，允许用户直观地解释和分析结果。由此产生的在线工具将是一个优秀的基于网络的教育工具，用于教育学生代谢生物化学，生物学，生物信息学，和代谢组学--训练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可在http://nashua.case.edu/上找到。

"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/.