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

聚糖和糖肽的液相色谱-质谱（LC-MS）分析方法 生物医学科学家可以使用质谱分析仪器。主 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可视化。 学术研究小组已经定义了用于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， 糖基化肽第二个是现有的糖科学质谱分析工具，不解决 高通量LC-MS数据集所需的全范围数据处理。因此，可以访问 通过当地蛋白质组学核心设施进行的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。其结果是严重的瓶颈 在生物医学中传播和使用糖科学LC-MS方法。 我们已经开发了三种用于糖科学质谱分析的软件程序，我们现在建议 设计和传播作为生物医学科学家可访问的解决方案。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 电子活化解离（ExD）串联质谱中的糖胺聚糖。GlycoDeNovo 根据ExD串联质谱确定支链聚糖拓扑结构和连接构型。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所需的所有模块， LC-MS分析、串联质谱分配和生成出版质量图形输出。 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）。用户可以选择将该软件作为桌面运行 应用程序，通过服务器，或作为GRITS插件。这些软件工具将是开源的 通过Github仓库。在目标1中，我们将开发GlycReSoft程序和相关工具， 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 将GAGfinder软件整合到一个完整的解决方案中，用于对ExD串联质谱中的糖胺聚糖进行测序 谱在目标3中，我们将开发一个基于GlycoDeNovo软件的管道，用于测序N-和O- 聚糖。

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.