CDI-Type II: MS-Omics Hub for Cyber-enabled Acceleration of Mass Spectrometry-based Metabolomics and Proteomics

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。网络支持的发现和创新(CDI)提案编号：0941143P/I：Christodoulos Floudas Institution：普林斯顿大学标题：CDI-Type II：MS-Omics Hub for Cyber-Enable Accelerate基于质谱学的代谢组学和蛋白质组学项目范围和智力优点：质谱学技术通过实现对蛋白质(蛋白质组学)和代谢物(代谢组学)的定量和全面评估，有可能对生物科学产生革命性的影响。然而，一个主要的挑战是将原始的质谱学数据转化为对生物学家有用的信息。该项目是通过为分析基于质谱学的代谢组学和蛋白质组学数据提供一个开源平台，利用网络基础设施加速生物发现，来改变蛋白质组学和代谢组学的努力。具体地说，该项目将开发一个统一的代谢物、多肽和蛋白质鉴定和定量平台(MS-Omics Hub)，该平台(1)允许用户输入来自不同仪器的质谱学数据，并返回给用户可分配的代谢物、多肽和蛋白质峰的身份和数量，(2)突出新的具有生物意义的物种，这些物种的重要性通过来自不同用户的数据的网络整合而出现，以及(3)为鉴定共价修饰的蛋白质提供增强的计算算法。这些算法将围绕一个整数线性优化框架，PI最近已经表明，该框架可以显著改善蛋白质组数据分析。MS-OMICS中心的效用将通过将其应用于由赠款团队和全国范围内的不同科学家生成的广泛数据来展示。智力价值：这一努力解决了阻止蛋白质组学和新陈代谢组学广泛影响生物学研究的障碍：从原始数据中提取化合物的身份和数量的困难。它进一步解决了蛋白质组数据分析的智力挑战方面：计算识别来自共价修饰蛋白质的峰。最后，它应用网络基础设施来加速识别来自新的、具有生物意义的代谢物和蛋白质共价修饰位点的峰。研究团队的多学科性质反映了所涉及的智力挑战的多样性：Floudas、Garcia和Rabinowitz分别来自普林斯顿大学的三个不同系(分别是化学工程、分子生物学和化学)，他们带来了横跨全球优化、科学计算、数学建模、蛋白质组学、代谢组学和分析化学的专业知识。他们对生物化学系统的全面、定量、可计算的分析的兴趣是统一的。更广泛的影响：这项研究有可能改变生物科学，加速蛋白质组学和代谢组学的进展，并使全国范围内的科学家能够接触到这些新兴领域的力量。对社会的影响：通过使更大的研究社区能够进行最先进的代谢组和蛋白质组数据分析，MS-OMICS中心将加快全球研究工作。通过提供具有生物学意义的峰的档案，它将加速发现新的代谢物和蛋白质共价修饰位点。这些可能包括新的生物标记物和生物活性化合物。改善代谢和蛋白质组能力的应用领域包括医药、药物开发、农业、生物能源和环境科学。研究与教育的整合：这一努力将使本科生和研究生参与研究计划的所有方面，包括代表人数不足的少数族裔和来自小型学院的来访学生。这些学生将接受质谱学、计算生物学、系统生物学和科学计算方面的培训。此外，作为一个开源平台，MS-OMICS中心将作为教育工具提供给全国的学者。PIS还计划举办年度用户大会。召开会议，与外部MS-OMICS中心用户进行互动和培训，并为中心招募新用户。扩大代表性不足的群体的代表性：每个私人投资机构都将积极招募少数族裔学生进行暑期研究。传播：除了通过标准渠道(期刊、审阅会议、会议)传播外，MS-OMICS中心还将通过质谱学专家网络、生物测试人员和夏季会议向社区介绍。MS-OMICS中心本身将是开源的(可在网络上获得代码)，世界各地的科学家都可以免费访问。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Cyber-Enabled Discovery and Innovation (CDI)Proposal Number: 0941143P/I: Christodoulos FloudasInstitution: Princeton UniversityTitle: CDI-Type II: MS-Omics Hub for Cyber-enabled Acceleration of Mass Spectrometry-based Metabolomics and ProteomicsScope of Project and Intellectual Merit:Mass spectrometry technology has the potential to revolutionize the biological sciences by enabling quantitative and comprehensive assessment of proteins (proteomics) and metabolites (metabolomics). A major challenge, however, is converting raw mass spectrometry data into information useful to biologists. This project represents an effort to transform proteomics and metabolomics by providing an open-source platform for analysis of mass spectrometry-based metabolomics and proteomics data which capitalizes on cyberinfrastructure to accelerate biological discovery. Specifically, the project will develop a unified platform for identification and quantitation of metabolites, peptides, and proteins (the MS-Omics Hub) that (1) allows the user to enter mass spectrometry data from diverse instrumentation and returns to the user identities and quantities of assignable metabolite, peptide, and protein peaks, (2) highlights novel, biologically significant species whose importance emerged through cyber-enabled integration of data from diverse users, and (3) provides enhanced computational algorithms for identification of covalently-modified proteins. These algorithms will revolve around an integer linear optimization framework that the PIs have recently shown can substantially improve proteomic data analysis. The utility of the MS-Omics Hub will be demonstrated through its application to a broad spectrum of data, generated both by the grant team and by a diversity of scientists nationwide. Intellectual Merit: This effort tackles a barrier preventing proteomics and metabolomics from broadly impacting biological research: the difficulty of extracting compound identities and quantities from raw data. It furthermore addresses the intellectually challenging aspect of proteomic data analysis: computational identification of peaks arising from covalently modified proteins. Finally, it applies cyber-infrastructure to accelerate the identification of peaks arising from novel, biologically-significant metabolites and protein covalent modification sites. The diversity of intellectual challenges involved is mirrored by the multidisciplinary nature of the research team: Floudas, Garcia, and Rabinowitz come from three different departments at Princeton University (Chemical Engineering, Molecular Biology, and Chemistry, respectively), and bring expertise spanning global optimization, scientific computing, mathematical modeling, proteomics, metabolomics, and analytical chemistry. They are unified by their interest in comprehensive, quantitative, computationally-enabled analysis of biochemical systems. Broader Impacts:This research has the potential to transform the biological sciences, by accelerating progress in proteomics and metabolomics and by rendering the power of these emerging fields accessible to a broad spectrum of scientists nationwide. Impact on Society: By enabling a larger research community to conduct state-of-the-art metabolomic and proteomic data analysis, the MS-Omics Hub will expedite global research efforts. By providing an archive of biologically significant peaks, it will accelerate discovery of novel metabolites and protein covalent modification sites. These will likely include novel biomarkers and bioactive compounds. Areas in which improved metabolomic and proteomic capabilities will be applied include medicine, drug discovery, agriculture, bioenergy, and environmental science. Integration of Research and Education: This effort will integrate participation of undergraduate and graduate students in all aspects of the research program, include underrepresented minorities and visiting students from small colleges. The students will receive training in mass spectrometry, computational biology, systems biology, and scientific computation. In addition, as an open-source platform, the MS-Omics Hub will be available as an educational tool to scholars nationwide. The PIs also plan to host an annual ?users? conference to interact with and train the outside MS-Omics Hub users, and to recruit new users to the Hub. Broaden Representation of Underrepresented Groups: Each of the PIs will actively recruit minority students for summer research. Dissemination: In addition to dissemination through standard channels (journals, refereed proceedings, conferences), the MS-Omics Hub will be introduced to the community through a network of mass spectrometry experts, biological beta-testers, and the summer conference. The MS-Omics Hub itself will be open-source (code available on web) and freely accessible to scientists worldwide.