Development of real-time control methodologies for tandem mass spectrometry

串联质谱实时控制方法的开发

• 批准号: 336805-2006
• 负责人: Wu, FangXiang
• 金额: $ 8.51万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Strategic Projects - Group
• 财政年份: 2007
• 资助国家: 加拿大
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=363686
• 关键词: Development; real; time; control; methodologies

One of the most important goals in the early detection of genomic-related disease, and the discovery ofassociated biomarkers, is to identify and characterize the proteins and protein complexes present in related celllines. Tandem mass spectrometry (MS/MS) is a powerful tool for identifying and comparing the proteinsexpressed in complex biological systems. However, the performance of mass spectrometers remains limited interms of the proportion of MS/MS data that can actually be interpreted. For example, up to 70% of the peptideMS/MS spectra generated by quadrupole-time of flight mass spectrometers, and up to 85% of those producedby ion trapping instruments, cannot be interpreted using any available technique. Furthermore, a great deal oftime is wasted in acquiring and attempting to interpret these poor-quality spectra. Based on our experience,literature review, and conversations with industry, it is apparent that the main obstacle to improvingperformance in protein mass spectrometry is the lack of fast, efficient algorithms capable of real-time detectionand/or selection of target peptide ions for fragmentation and MS/MS analysis. The goal of the proposedresearch is to overcome this challenge, and hence, increase throughput and efficiency for protein massspectrometry. This will be achieved by developing (a) an efficient algorithm for assessing the quality of peptideMS/MS spectra, and (b) a fast and accurate algorithm for on-line protein identification using verified peptideMS/MS spectra. The proposed research will significantly improve the performance of mass spectrometers byenabling the development of real-time control methodologies based upon the algorithms developed in thisproposal. In providing such advanced methodologies for high-throughput identification of proteins and proteinbiomarkers, this project will also make a major contribution to Canadian health research, while promotingacademic, industrial economic activity in Canada.

早期检测基因组相关疾病和发现相关生物标志物的最重要目标之一是鉴定和表征相关细胞系中存在的蛋白质和蛋白质复合物。串联质谱 (MS/MS) 是识别和比较复杂生物系统中表达的蛋白质的强大工具。然而，就实际可解释的 MS/MS 数据比例而言，质谱仪的性能仍然有限。例如，四极杆飞行时间质谱仪生成的肽 MS/MS 谱中高达 70% 的肽 MS/MS 谱以及离子捕获仪器产生的肽 MS/MS 谱中高达 85% 的谱无法使用任何可用技术进行解释。此外，大量的时间被浪费在获取和尝试解释这些低质量的光谱上。根据我们的经验、文献综述以及与业界的对话，很明显，提高蛋白质质谱分析性能的主要障碍是缺乏能够实时检测和/或选择目标肽离子进行裂解和 MS/MS 分析的快速、高效的算法。拟议研究的目标是克服这一挑战，从而提高蛋白质质谱的通量和效率。这将通过开发 (a) 一种用于评估肽 MS/MS 谱图质量的有效算法，以及 (b) 一种使用经过验证的肽 MS/MS 谱图进行在线蛋白质鉴定的快速而准确的算法来实现。所提出的研究将通过基于本提案中开发的算法开发实时控制方法来显着提高质谱仪的性能。通过提供用于蛋白质和蛋白质生物标志物的高通量鉴定的先进方法，该项目还将为加拿大的健康研究做出重大贡献，同时促进加拿大的学术和工业经济活动。