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: 9751068
• 负责人: Yehia Ibrahim
• 金额: $ 42.57万
• 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 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751068
• 关键词: Address; Advanced Malignant Neoplasm; Biological; Clinical; Complex; DNA Sequence Alteration; Data; Data Quality; Detection; Development; Devices; Fractionation; Future; Hour; 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; bioinformatics tool; clinical application; computerized data processing; data acquisition; design; genetic regulatory protein; improved; informatics tool; ion mobility; ion source; liquid chromatography mass spectrometry; novel; novel strategies; operation; 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.

项目概要/摘要 该项目的目标是评估新的高通量和超灵敏平台 这将实现更有效和更高通量的蛋白质组学测量，以支持和 推进癌症研究。新平台将提供分辨率更高的离子 迁移谱 (IMS) 分离效果优于当前平台。这项工作还利用了 通过将这些新功能与更多功能相结合，我们实验室以前的发展 灵敏高效的离子源和高精度质谱技术。 IMS的分辨率 通过使用施加到极长距离的电行波，所实现的效果将大大提高 基于无损离子操纵结构（SLIM）的路径设计，同时还能够 达到非常高的灵敏度。该平台将提供大约两份订单 类似或更好测量的测量吞吐量的大幅改进 与传统凝聚相液相色谱-质谱相比的覆盖范围、定量等 光谱分析 (LC-MS) 平台，可在数小时内分析数千个样品，而不是 比目前几周多。我们还将调整和完善我们开发的生物信息学工具 实验室提供自动化、高效的数据处理。最后，该平台将 利用复杂的临床样本对蛋白质组肽/蛋白质覆盖度进行评估， 测量吞吐量、重复分析的 CV 和平台稳健性以及比较 到我们实验室提供的领先的传统 LC-MS 平台。

项目成果

Implementation of Ion Mobility Spectrometry-Based Separations in Structures for Lossless Ion Manipulations (SLIM).

• DOI: 10.1007/978-1-0716-1811-0_23
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)