Quorum: glycopeptide discovery via mass spectrometry and spectral networking

糖基化是一种普遍存在的修饰，估计可以修饰超过50%的 人类蛋白质，是宿主-病原体相互作用的关键组成部分，适应性和 与生俱来的免疫力和治疗发展。糖蛋白的计算工具 分析简化了对可能的多糖结构的假设，限制了它们的 实用程序在许多情况下。这项提案旨在全面描述 糖蛋白，包括新的和意想不到的多糖，与数字蛋白质组学的法定人数 质谱学数据分析软件，并启用进一步的糖蛋白 通过开发发现的靶向抗体进行表征 糖肽。 Quorum软件建立在光谱网络范例的基础上，该范例假设 结构相似的分子产生相似的质谱图。在糖肽的法定人数中 分析表明，网络光谱代表了同一糖基上不同的糖链结构 一种蛋白质。与传统的糖肽鉴定方法类似，Quorum 将糖肽谱与蛋白质序列数据库和糖链结构进行匹配 数据库。与传统方法不同，Quorum采用了严格的错误发现 靶标诱饵分析中基于不同糖链结构的速率计算。此外, Quorum通过传播标识来提高糖肽的识别率 沿着网络中的边缘，能够发现不在网络中的多糖结构 该结构数据库可以是完全新颖的。 Quorum将以糖蛋白标准为基准，特征良好 NIST单抗标准物质和总免疫球蛋白，将建立一个 发现光谱网络变异糖肽的基线。Quorum软件是 部署到云，作为我们可扩展平台Quorum Cloud的一部分，其中 糖蛋白分析是通用光谱网络分析的一个插件。应征入伍测试员 云平台在糖化工程、糖化浓缩分析、 和治疗的发展。

Glycosylation is a pervasive modification estimated to modify more than 50% of human proteins and is a key component of host-pathogen interactions, adaptive and innate immunity, and therapeutic development. Computational tools for glycoprotein analysis make simplifying assumptions about possible glycan structures, limiting their utility in many scenarios. This proposal aims to comprehensively characterize glycoproteins, including novel and unexpected glycans, with Digital Proteomics’ Quorum mass spectrometry data analysis software, and enable further glycoprotein characterization through the development of antibodies targeting discovered glycopeptides. The Quorum software builds on the spectral networking paradigm that posits that structurally similar molecules produce similar mass spectra. In Quorum for glycopeptide analysis, networked spectra represent different glycan structures on the same glycosite of a protein. Similar to traditional approaches to glycopeptide identification, Quorum matches glycopeptide spectra to a protein sequence database and glycan structure database. Unlike traditional approaches, Quorum employs a rigorous false-discovery rate calculation based on variant glycan structures in target-decoy analysis. In addition, Quorum increases the identification rate of glycopeptides by propagating identifications along edges in the network, enabling the discovery of glycan structures that are not in the structure database and may be completely novel. Quorum will be benchmarked on glycoprotein standards, well-characterized NIST monoclonal antibody reference material, and total IgG which will establish a baseline for spectral network variant glycopeptide discovery. The Quorum software is deployed to the cloud, as part of our extensible platform Quorum Cloud, where the glycoprotein analysis is a plugin to generic spectral networking analysis. Enlisted testers of the cloud platform have applications in glycoengineering, glycoenrichment assays, and therapeutic development.