Using trapped ion mobility to synchronize ions in data-independent acquisition (DIA) mass spectrometry
在数据独立采集 (DIA) 质谱分析中使用捕获离子淌度同步离子
基本信息
- 批准号:RGPIN-2019-06833
- 负责人:
- 金额:$ 2.48万
- 依托单位:
- 依托单位国家:加拿大
- 项目类别:Discovery Grants Program - Individual
- 财政年份:2020
- 资助国家:加拿大
- 起止时间:2020-01-01 至 2021-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Mass spectrometry (MS) has been used extensively in proteomics for the analysis of complex samples, such as clinical or environmental samples as well as whole cell lysates. Specifically, in bottom-up proteomics, proteins are extracted from a biological sample and enzymatically cleaved before analysis using an on-line system of liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).
In LC-MS/MS based bottom up proteomics, state-of-the-art mass spectrometers efficiently transfer ions into the vacuum, but make use of only a small fraction of the ion beam for mass analysis. In traditional data-dependent acquisition (DDA), only a single precursor ion is selected for fragmentation, thus effectively filtering out over 99.9% of the mass range up to 2000 Da. To sample fragment ions more comprehensively and reproducibly than DDA methods, we have recently developed SWATH-MS which uses data-independent acquisition (DIA). However, also SWATH-MS methods employ relatively small mass isolation windows to increase specificity (e.g. 25 m/z) and thus utilize less than 1.25% of all available ions within a typical duty cycle. Thus, while reproducibility and sensitivity is increased with DIA, typical DIA methods such as SWATH-MS still have relatively low ion beam efficiency and over 98% of the ions can never reach the mass analyzer. However, in principle, a 100% duty cycle (until the TOF analyzer) could be achieved using trapping devices that release the ions at the precise time of analysis. This principle has been implemented for DDA analysis in the “Parallel Accumulation SErial Fragmentation” (DDA-PASEF) method by our collaborators.
Here we propose to implement a novel method termed DIA-PASEF using data-independent acquisition in order to increase the ion usage of DIA methods and thus further increase their sensitivity and throughput. This will be achieved in the following three aims:
Aim 1: Computationally simulate and implement a novel acquisition scheme that exploits the coupling between ion mobility and m/z for DIA-PASEF.
Aim 2: Develop a targeted analysis strategy for DIA-PASEF data to allow analysis of the four dimensional data space (signal intensity, retention time, ion mobility and m/z).
Aim 3: : Development of an untargeted approach for unbiased analysis of DIA-PASEF data.
The potential impact of this research is a crucial improvement of MS, a core analytical technology used in research, with the potential to increase sensitivity, speed of analysis and accuracy through our improvements in duty cycle. The anticipated result of this research lies in an improved method to comprehensively sample ionized molecules and their fragments. The impact will range from basic research into the molecular behavior of biological systems under laboratory conditions to applied areas in clinical and pharmacological research, where MS can be used to directly analyze clinical samples such as tissue and blood plasma.
质谱(MS)已广泛用于蛋白质组学中,用于分析复杂样品,例如临床或环境样品以及全细胞裂解物。具体而言,在自下而上的蛋白质组学中,从生物样品中提取蛋白质,并在使用液相色谱-串联质谱(LC-MS/MS)的在线系统进行分析之前进行酶促裂解。
在基于LC-MS/MS的自下而上蛋白质组学中,最先进的质谱仪有效地将离子转移到真空中,但仅利用离子束的一小部分进行质量分析。在传统的数据依赖采集(DDA),只有一个单一的前体离子被选择用于碎片,从而有效地过滤出超过99.9%的质量范围高达2000 Da。样品碎片离子更全面和重现性比DDA的方法,我们最近开发了SWATH-MS使用数据独立采集(DIA)。然而,SWATH-MS方法也采用相对小的质量隔离窗口来增加特异性(例如25 m/z),因此在典型的占空比内利用小于1.25%的所有可用离子。因此,虽然DIA提高了再现性和灵敏度,但典型的DIA方法(例如SWATH-MS)仍然具有相对低的离子束效率,并且超过98%的离子永远无法到达质量分析器。然而,原则上,使用在分析的精确时间释放离子的捕获装置可以实现100%的占空比(直到TOF分析仪)。我们的合作者已经在“并行累积序列片段化”(DDA-PASEF)方法中实现了这一原理用于DDA分析。
在这里,我们提出了一种新的方法,称为DIA-PASEF使用数据独立的采集,以增加离子的使用DIA方法,从而进一步提高其灵敏度和吞吐量。这将通过以下三个目标实现:
目的1:计算模拟和实现一种新的采集方案,利用离子迁移率和m/z之间的耦合DIA-PASEF。
目标二:为DIA-PASEF数据制定有针对性的分析策略,以分析四维数据空间(信号强度、保留时间、离子迁移率和m/z)。
目标3:制定一种无针对性的方法,对国家情报局-PASEF数据进行无偏分析。
这项研究的潜在影响是对MS的关键改进,MS是研究中使用的核心分析技术,通过我们对占空比的改进,有可能提高灵敏度,分析速度和准确性。本研究的预期成果在于改进了对电离分子及其碎片进行全面采样的方法。其影响范围将从实验室条件下生物系统分子行为的基础研究到临床和药理学研究的应用领域,其中MS可用于直接分析组织和血浆等临床样品。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rost, Hannes其他文献
Automated Workflow for Peptide-Level Quantitation from DIA/SWATH-MS Data
- DOI:
10.1007/978-1-0716-1024-4_31 - 发表时间:
2021-01-01 - 期刊:
- 影响因子:0
- 作者:
Gupta, Shubham;Rost, Hannes - 通讯作者:
Rost, Hannes
DIAlignR Provides Precise Retention Time Alignment Across Distant Runs in DIA and Targeted Proteomics
- DOI:
10.1074/mcp.tir118.001132 - 发表时间:
2019-04-01 - 期刊:
- 影响因子:7
- 作者:
Gupta, Shubham;Ahadi, Sara;Rost, Hannes - 通讯作者:
Rost, Hannes
Identification of a Set of Conserved Eukaryotic Internal Retention Time Standards for Data-independent Acquisition Mass Spectrometry
- DOI:
10.1074/mcp.o114.042267 - 发表时间:
2015-10-01 - 期刊:
- 影响因子:7
- 作者:
Parker, Sarah J.;Rost, Hannes;Aebersold, Ruedi - 通讯作者:
Aebersold, Ruedi
DIAproteomics: A Multifunctional Data Analysis Pipeline for Data-Independent Acquisition Proteomics and Peptidomics
- DOI:
10.1021/acs.jproteome.1c00123 - 发表时间:
2021-06-21 - 期刊:
- 影响因子:4.4
- 作者:
Bichmann, Leon;Gupta, Shubham;Rost, Hannes - 通讯作者:
Rost, Hannes
Rost, Hannes的其他文献
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{{ truncateString('Rost, Hannes', 18)}}的其他基金
Using trapped ion mobility to synchronize ions in data-independent acquisition (DIA) mass spectrometry
在数据独立采集 (DIA) 质谱分析中使用捕获离子淌度同步离子
- 批准号:
RGPIN-2019-06833 - 财政年份:2022
- 资助金额:
$ 2.48万 - 项目类别:
Discovery Grants Program - Individual
Using trapped ion mobility to synchronize ions in data-independent acquisition (DIA) mass spectrometry
在数据独立采集 (DIA) 质谱分析中使用捕获离子淌度同步离子
- 批准号:
RGPIN-2019-06833 - 财政年份:2021
- 资助金额:
$ 2.48万 - 项目类别:
Discovery Grants Program - Individual
Using trapped ion mobility to synchronize ions in data-independent acquisition (DIA) mass spectrometry
在数据独立采集 (DIA) 质谱分析中使用捕获离子淌度同步离子
- 批准号:
DGECR-2019-00378 - 财政年份:2019
- 资助金额:
$ 2.48万 - 项目类别:
Discovery Launch Supplement
Using trapped ion mobility to synchronize ions in data-independent acquisition (DIA) mass spectrometry
在数据独立采集 (DIA) 质谱分析中使用捕获离子淌度同步离子
- 批准号:
RGPIN-2019-06833 - 财政年份:2019
- 资助金额:
$ 2.48万 - 项目类别:
Discovery Grants Program - Individual
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Using trapped ion mobility to synchronize ions in data-independent acquisition (DIA) mass spectrometry
在数据独立采集 (DIA) 质谱分析中使用捕获离子淌度同步离子
- 批准号:
RGPIN-2019-06833 - 财政年份:2019
- 资助金额:
$ 2.48万 - 项目类别:
Discovery Grants Program - Individual