Developing MRM-based proteomics software

开发基于 MRM 的蛋白质组学软件

• 批准号: 7744603
• 负责人: Jayson Andrew Falkner
• 金额: $ 15.31万
• 依托单位: SINGLE ORGANISM SOFTWARE, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-26 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7744603
• 关键词: Algorithms; Amino Acid Sequence; Area; Arts; Biological Assay; Biological Markers; Collaborations; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Computer software; Data; Data Collection; Data Set; Databases; Development; Diagnosis; Discipline; Disease; Drug Industry; Early Diagnosis; Equation; Funding; Goals; Grant; Health Personnel; Heart Diseases; Hormones; Human; Imagery; Institution; Label; Laboratories; Libraries; Malignant Neoplasms; Manuals; Manufacturer Name; Mass Spectrum Analysis; Measurement; Measures; Medical; Methodology; Methods; Mission; Peptide Sequence Determination; Peptides; Pesticides; Pharmaceutical Preparations; Proteins; Proteomics; Relative (related person); Research; Research Design; Research Personnel; Resources; Running; Sales; Schedule; Stable Isotope Labeling; Techniques; Testing; Time; United States National Institutes of Health; Vendor; Visualization software; Work; base; design; file format; flexibility; human disease; instrument; instrumentation; interest; multiple reaction monitoring; next generation; posters; programs; public health relevance; research study; small molecule; software development; symposium; tandem mass spectrometry; technology development; tool; trend

DESCRIPTION (provided by applicant): Multiple reaction monitoring (MRM) is a highly selective, high sensitivity mass spectrometry mode for detecting the presence of particular species in a mixture. In the pharmaceutical industry, many small molecule analytes (e.g. drug metabolites, hormones, and pesticides) are routinely measured in high throughput with MRM's great precision. MRM based assays are now being tested and developed for large biomolecules (peptides and proteins) in the field of proteomics. These advances are significant because MRM proteomics provides a high-throughput, flexible, and relatively inexpensive alternative to traditional protein assays. The use of MRM proteomics is particularly appealing compared to traditional protein anti-body based approaches because of the minimal time required to design and test an assay (fast instrument configuration) and the ability to multiplex thousands of assays. This proposal will develop a next-generation MRM software package that will provide full support during all aspects of MRM experiments, including transition selection, instrument optimization, data collection, and curation. The long-term goal is to develop a licensable, instrument independent software package for users with any level of expertise in targeted proteomics. Testing and development will be done through collaboration with research groups at the forefront of technology development in the field. The software suite will fill a void for proteomics laboratories globally as a comprehensive software package currently does not exist. The state of the art in MRM proteomics includes both focused academic applications as well as vendor-specific basic software packages bundled with instrument sales. However, the functionality provided by these tools is limited and few if any commercial quality tools are accessible to researchers looking to develop targeted proteomic efforts. The timing of this proposal is opportune to capitalize on the growing interest about MRM in the proteomics field where such an application will accelerate further use of MRM-based assays. This proposal's objective and implementation of the goals aligns with the NIH's mission in two key areas. First, the described MRM software would significantly accelerate development of MRM-based assays for protein level biomarkers and take full advantage of current instrumentation. The MRM approach is an established, well received technique and the discipline of proteomics is just starting to utilize the practice. The most recent ASMS conference included dozens of posters and talks describing MRM developments in the proteomics field. In addition, there are currently over 20 funded NIH grants supporting MRM or targeted proteomic efforts listed in the CRISP database. Second, the proposal will directly aid at least two research groups at leading institutions that are using the MRM methodology in proteomic analyses of human diseases. These collaborations will accelerate the respective groups' advances in early detection of heart disease and various human cancers. PUBLIC HEALTH RELEVANCE: Protein identification and abundance measurement enables researchers and medical personnel to better diagnose and understand medical conditions. This proposal develops software that finds the subtle changes in proteins that may cause disease.

描述（由申请人提供）：多反应监测（MRM）是一种高选择性、高灵敏度的质谱模式，用于检测混合物中特定物质的存在。在制药行业中，许多小分子分析物（例如药物代谢物、激素和农药）通常需要通过 MRM 的高精度进行高通量测量。目前正在蛋白质组学领域针对大生物分子（肽和蛋白质）测试和开发基于 MRM 的检测方法。这些进步意义重大，因为 MRM 蛋白质组学为传统蛋白质检测提供了高通量、灵活且相对便宜的替代方案。与传统的基于蛋白质抗体的方法相比，MRM 蛋白质组学的使用特别有吸引力，因为设计和测试测定所需的时间最短（快速仪器配置）并且能够进行数千种测定。该提案将开发下一代 MRM 软件包，该软件包将在 MRM 实验的各个方面提供全面支持，包括过渡选择、仪器优化、数据收集和管理。长期目标是为具有任何目标蛋白质组学专业水平的用户开发一个可授权的、独立于仪器的软件包。测试和开发将通过与该领域技术开发前沿的研究小组合作来完成。该软件包将填补全球蛋白质组学实验室的空白，因为目前尚不存在全面的软件包。 MRM 蛋白质组学的最新技术包括重点学术应用以及与仪器销售捆绑在一起的特定于供应商的基本软件包。然而，这些工具提供的功能是有限的，并且对于寻求开发有针对性的蛋白质组学研究的研究人员来说，几乎没有商业质量的工具可用。该提案的时机恰逢其时，充分利用了蛋白质组学领域对 MRM 日益增长的兴趣，此类应用将加速基于 MRM 的检测的进一步使用。该提案的目标和目标的实施与 NIH 在两个关键领域的使命相一致。首先，所描述的 MRM 软件将显着加速基于 MRM 的蛋白质水平生物标志物检测的开发，并充分利用当前的仪器。 MRM 方法是一种成熟的、广受好评的技术，蛋白质组学学科刚刚开始利用这种实践。最近的 ASMS 会议包括数十张海报和演讲，描述了蛋白质组学领域 MRM 的发展。此外，目前有超过 20 项 NIH 资助支持 MRM 或 CRISP 数据库中列出的目标蛋白质组学工作。其次，该提案将直接帮助领先机构中至少两个使用 MRM 方法进行人类疾病蛋白质组学分析的研究小组。这些合作将加速各自小组在心脏病和各种人类癌症的早期检测方面取得进展。公共健康相关性：蛋白质鉴定和丰度测量使研究人员和医务人员能够更好地诊断和了解医疗状况。该提案开发的软件可以发现可能导致疾病的蛋白质的细微变化。