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; 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 - 质谱法（LC-MS）的分析方法是 成熟，可供生物医学科学家使用，可以使用质谱仪器。主要 非糖科学家采用这种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。 学术研究小组已经定义了解释质谱算法方法 糖科学领域。尽管做出了这项努力，但仍有很少的实用，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使肽特定的假设排除了释放的聚糖和 糖基化的肽。第二个是可用的糖科学质谱分析工具，不要解决 高吞吐量LC-MS数据集所需的数据处理范围。因此，用户可以访问 通过本地蛋白质组学核心设施通过质谱法无法使用适当的软件工具 处理液相染料 - 质谱（LC-MS）数据集。结果是严重的瓶颈 用于传播和使用生物医学中的糖科学LC-MS方法。 我们已经开发了三个用于糖科学质谱的软件程序，我们现在建议 工程师并将其作为生物医学科学家的可访问解决方案。 Glycresoft处理聚糖 糖蛋白的分析和综合法。 Gagfinder是用于测序的第二代算法 来自电子激活解离（EXD）串联质量光谱的糖胺聚糖。糖 确定来自EXD串联质谱的分支聚糖拓扑和连锁构型。我们 提议设计和传播开源管道，以处理聚糖和糖肽LC-MS 数据。这将包括处理与供应商无关的质谱数据所需的所有模块，执行 LC-MS分析，串联质谱分配并生成出版物质量图形输出。 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 使用现代聚糖代表标准并与国际聚糖结构进行沟通 存储库和名称空间（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Grits工具箱插件。软件工具将提供开源 通过GitHub存储库。在AIM 1中，我们将开发我们的Glycresoft程序和相关工具 糖蛋白酶学和糖蛋白质组学LC-MS数据分析的完整解决方案。在AIM 2中，我们将发展 gagfinder软件成一个完整的解决方案，用于测序来自EXD串联质量的糖胺聚糖 光谱。在AIM 3中，我们将基于我们的糖二烯诺沃软件开发一条管道，用于对N-和O-进行测序。 聚糖。