PhosphoExplorer: Software for annotating and analyzing phosphoproteomics data

摘要 从质谱学实验中获得的磷酸蛋白质组学(PP)数据具有独特的能力 全面了解细胞信号通路和网络。是这样的 全球范围的信息将为发育中的细胞信号提供独特的见解 和分化，这将极大地促进我们对生物学的理解。虽然 使用质谱仪收集PP数据的技术正在迅速发展， 用于分析PP数据的计算工具没有跟上步伐。管理层和 对数以千计的磷酸盐信息的注释如果手动进行是无效的，并且 必须是自动化的，并在视觉上呈现给用户。此外，虽然许多有效的工具 对于基因和蛋白质表达数据的路径和网络分析，PP的工具有 相对不发达。根据PA-14-155提交的这项提案打算推进 通过开发、测试和传播磷蛋白和蛋白质的软件来实现PP领域 亚磷酸盐的鉴定、定位、注释、路径和网络分析。结果是 本研究将更快速有效地将PP数据转化为有用的知识 推进生物科学和药物开发。 这项研究将包括三个目标： 目的1：亚磷酸盐工具PhosMS-GF和PhosPhoExplorer的开发与测试 从质谱学数据中进行鉴定和注释。这一目标将提供一种工具，可以 将质谱学数据与多个亚磷酸盐数据库统一起来，扩大 PP鉴定改进分析。 目的2：开发和测试一种磷蛋白集浓缩分析工具箱和 磷蛋白相互作用和网络分析工具包作为PhosPhoExplorer的扩展。 这一目标将为PP数据的系统级分析提供一个独特的工具包。 目标3：开发、测试、校准和发布用于系统级注释和 磷酸蛋白质组学数据的分析。这一目标将把强大的开源软件交付给 用户社区。 因为目前已有PhosPhoExplorer的原型版本，并在凯斯的内部使用 西部储备大学，我们毫不怀疑，在三年的时间里，我们可以完成 上述改进并将工具交到了全国范围内的用户群手中，这些用户 积极收集和分析PP数据集。

Abstract Phosphoproteomics (PP) data derived from mass spectrometry experiments has a unique ability to interrogate cellular signaling pathways and networks in a comprehensive manner. Such information on a global scale will provide unique insights into cellular signaling in development and differentiation, which will considerably advance our understanding of biology. Although technologies for collecting PP data using mass spectrometry are advancing rapidly, computational tools for analyzing the PP data are not keeping pace. The management and annotation of information on thousands of phosphosites is ineffective if conducted manually and must be automated and visually presented to the user. In addition, although many effective tools exist for pathway and network analysis of gene and protein expression data, the tools for PP are relatively underdeveloped. This proposal, submitted under PA-14-155, intends to advance the field of PP by developing, testing, and disseminating software for phosphoprotein and phosphosite identification, localization, annotation, pathway and network analysis. The outcome of this research will be more rapid and effective translation of PP data into useful knowledge for advancing biological science and drug development. The research will comprise 3 Aims: Aim 1: Development and testing of PhosMS-GF+ and PhosphoExplorer, a tool for phosphosite identification and annotation from mass spectrometry data. This aim will provide a tool that can unify mass spectrometry data with multiple phosphosite databases and extend the number of PP identifications improving analyses. Aim 2: Development and testing of a phosphoprotein set enrichment analysis tool kit and phosphoprotein interaction and network analysis tool kit as expansions of PhosphoExplorer. This aim will provide an unique toolkit for systems level analysis of PP data. Aim 3: Develop, test, calibrate, and release software tools for systems-level annotation and analysis of phosphoproteomics data. This aim will deliver robust open-source software to the user community. As prototype versions of PhosphoExplorer currently exist and are in use in-house at Case Western Reserve University, we have no doubt that over a three-year period we can complete the above improvements and put the tools in the hands of a national cohort of users that are actively collecting and analyzing PP datasets.