High Resolution High Throughput Proteomics Platform for Cancer Research

用于癌症研究的高分辨率高通量蛋白质组学平台

• 批准号: 9534591
• 负责人: Yehia Ibrahim
• 金额: $ 41.65万
• 依托单位: BATTELLE PACIFIC NORTHWEST LABORATORIES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9534591
• 关键词: Address; Advanced Malignant Neoplasm; Bioinformatics; Biological; Clinical; Complex; DNA Sequence Alteration; Data; Data Quality; Detection; Development; Devices; Fractionation; Future; Hour; Informatics; Ions; Laboratories; Length; Liquid Chromatography; Mass Spectrum Analysis; Measurement; Peptides; Performance; Phase; Population; Population Study; Proteins; Proteome; Proteomics; Reproducibility; Resolution; Route; Sampling; Spectrometry; Speed; Structure; Technology; Time; Travel; Work; anticancer research; base; clinical application; computerized data processing; data acquisition; design; genetic regulatory protein; improved; ion mobility; ion source; liquid chromatography mass spectrometry; novel; novel strategies; operation; tool; tumor

PROJECT SUMMARY/ABSTRACT The objective of this project is to evaluate a new high-throughput and ultra-sensitive platform that will enable more effective and higher throughput proteomics measurements to support and advance cancer research. The new platform will provide substantially higher resolution ion mobility spectrometry (IMS) separations than current platforms. This work also leverages previous developments at our laboratory by combining these new capabilities with more sensitive and efficient ion source and high accuracy MS technologies. The resolution of the IMS achieved will be greatly increased by using electric traveling waves applied to an extremely long path design based upon Structures for Lossless Ion Manipulations (SLIM), while also enabling very high sensitivity to be achieved. The platform will provide approximately two orders of magnitude improvement in measurement throughput for similar or better measurement coverage, quantification, etc. over conventional condensed-phase liquid chromatography-mass spectrometry (LC-MS) platforms, enabling thousands of samples to be analyzed in hours, rather than weeks as at present. We will also adapt and refine bioinformatics tools developed in our laboratory to provide automated and efficient data processing. Finally, the platform will be evaluated utilizing complex clinical samples in terms of proteomic peptide/protein coverage, measurement throughput, CVs of replicate analyses and platform robustness and in comparison to leading-edge conventional LC-MS platforms available in our laboratory.

项目摘要/摘要 该项目的目的是评估一个新的高通量和超敏感平台 这将使更有效和更高的吞吐量蛋白质组学测量以支持和 预先癌症研究。新平台将提供更高的分辨率离子 移动光谱法（IMS）的分离比当前平台。这项工作也利用 通过将这些新功能与更多的更多功能相结合，在我们实验室的先前发展 敏感有效的离子源和高精度MS技术。 IMS的解决方案 通过使用应用于极长的电波，实现的实现将大大增加 基于无损离子操纵结构的路径设计（Slim），同时也可以 要实现的敏感性非常高。该平台将提供大约两个订单 相似或更好测量的测量吞吐量的幅度改善 覆盖范围，定量等在常规凝聚相液相色谱质量上 光谱法（LC-MS）平台，可以在数小时内分析成千上万的样本 比目前的几周。我们还将适应和完善我们开发的生物信息学工具 实验室提供自动化和有效的数据处理。最后，平台将是 根据蛋白质组学肽/蛋白质覆盖范围，评估了使用复杂的临床样品， 测量吞吐量，重复分析的简历和平台鲁棒性以及相比 到我们实验室可用的领先传统LC-MS平台。