An open-source software suite for processing glycomics and glycoproteomics mass spectral data

用于处理糖组学和糖蛋白质组学质谱数据的开源软件套件

• 批准号: 9391486
• 负责人: JOSEPH ZAIA
• 金额: $ 41.5万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-14 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9391486
• 关键词: Adoption; Algorithms; Chondroitin Sulfates; Client; Communities; Complex; Computer software; Core Facility; Data; Data Analyses; Data Set; Development; Dissociation; Electron Transport; Electrons; Engineering; Environment; Fourier transform ion cyclotron resonance; Generations; Genes; Glycopeptides; Glycoproteins; Glycosaminoglycans; Heparitin Sulfate; Imagery; Individual; International; Internet; Isomerism; Keratan Sulfate; Libraries; Mass Spectrum Analysis; Methods; Modernization; Output; Peptides; Polysaccharides; Problem Solving; Process; Proteomics; Public Domains; Publications; Research; Resources; Running; Sampling; Software Tools; Structure; Technology; Translating; Vendor; Visual; analytical method; base; biomedical scientist; cohort; commercialization; computerized data processing; data acquisition; experimental study; glycoproteomics; graphical user interface; instrument; interest; liquid chromatography mass spectrometry; open source; operation; polymerization; programs; repository; software development; tandem mass spectrometry; tool

Analytical methods for liquid chromatography-mass spectrometry (LC-MS) of glycans and glycopepeptides are mature and available to biomedical scientists with access to mass spectrometry instruments. The primary barrier to the adoption of such methods by non-glycoscientists is the lack of tools for processing the raw LC- MS data, evaluating the results, and results visualizations that present those findings in a systematic fashion. Academic research groups have defined algorithmic approaches for interpretation mass spectra in the glycoscience domain. Despite this effort, there remains a paucity of practical, user accessible tools for processing glycan and glycopeptide mass spectral data. The first problem is that public domain and commercial proteomics workflows make peptide-specific assumptions that exclude released glycans and glycosylated peptides. The second is that available glycoscience mass spectral analysis tools, do not address the full scope of data processing needed for high throughput LC-MS data sets. Thus, users with access to mass spectrometry through local proteomics core facilities do not have access to adequate software tools for processing the liquid-chromatography-mass spectrometry (LC-MS) datasets. The result is a serious bottleneck for dissemination and use of glycoscience LC-MS methods in biomedicine. We have developed three software programs for glycoscience mass spectrometry that we now propose to engineer and disseminate as accessible solutions for biomedical scientists. GlycReSoft processes glycan profiling and integrated omics of glycoproteins. GAGfinder is a second generation algorithm for sequencing glycosaminoglycans from electron activated dissociation (ExD) tandem mass spectra. GlycoDeNovo determines branched glycan topologies and linkage configurations from ExD tandem mass spectra. We propose to engineer and disseminate open source pipelines for processing glycan and glycopeptide LC-MS data. This will include all modules necessary to process vendor-independent mass spectrometry data, perform LC-MS profiling, tandem mass spectrometry assignments and generate publication quality graphical outputs. We will deliver software that builds on available data standards and MS processing libraries. The software will use modern glycan representation standards and communicate with the international glycan structure repository and namespace (GlyTouCan). Users will have the option of running the software as a desktop application, through a server, or as a GRITS Toolbox plugin. The software tools will be available open source through a Github repository. In Aim 1, we will develop our GlycReSoft program and related tools into a complete solution for glycomics and glycoproteomics LC-MS data analysis. In Aim 2, we will develop GAGfinder software into a complete solution for sequencing glycosaminoglycans from ExD tandem mass spectra. In Aim 3, we will develop a pipeline based on our GlycoDeNovo software for sequencing N- and O- glycans.

聚糖和糖肽的液相色谱-质谱 (LC-MS) 分析方法是 成熟且可供使用质谱仪器的生物医学科学家使用。初级 非糖科学家采用此类方法的障碍是缺乏处理原始 LC-的工具 MS 数据、评估结果以及以系统方式呈现这些发现的结果可视化。 学术研究小组已经定义了解释质谱的算法方法 糖科学领域。尽管做出了这些努力，但仍然缺乏实用的、用户可访问的工具 处理聚糖和糖肽质谱数据。第一个问题是公共领域和 商业蛋白质组学工作流程做出肽特异性假设，排除释放的聚糖和 糖基化肽。第二是现有的糖科学质谱分析工具不解决 高通量 LC-MS 数据集所需的全方位数据处理。因此，有权访问的用户 通过当地蛋白质组学核心设施进行质谱分析无法获得足够的软件工具 处理液相色谱-质谱 (LC-MS) 数据集。结果出现了严重的瓶颈 用于糖科学 LC-MS 方法在生物医学中的传播和使用。 我们已经开发了三个用于糖科学质谱分析的软件程序，我们现在建议将其用于 设计并传播为生物医学科学家可用的解决方案。 GlycReSoft 处理聚糖 糖蛋白的分析和整合组学。 GAGfinder 是第二代测序算法 来自电子激活解离 (ExD) 串联质谱的糖胺聚糖。 GlycoDeNovo 从 ExD 串联质谱确定支链聚糖拓扑和连接构型。我们 建议设计和传播用于处理聚糖和糖肽 LC-MS 的开源管道 数据。这将包括处理独立于供应商的质谱数据、执行 LC-MS 分析、串联质谱分配并生成出版质量的图形输出。 我们将提供基于可用数据标准和 MS 处理库的软件。该软件将 使用现代聚糖表示标准并与国际聚糖结构进行沟通 存储库和命名空间 (GlyTouCan)。用户可以选择将软件作为桌面运行 应用程序，通过服务器，或作为 GRITS Toolbox 插件。软件工具将开源 通过 Github 存储库。在目标 1 中，我们将把 GlycReSoft 程序和相关工具开发成一个 糖组学和糖蛋白质组学 LC-MS 数据分析的完整解决方案。在目标 2 中，我们将开发 GAGfinder 软件成为 ExD 串联质谱中糖胺聚糖测序的完整解决方案 光谱。在目标 3 中，我们将开发基于 GlycoDeNovo 软件的管道，用于对 N- 和 O- 进行测序 聚糖。