Quorum: glycopeptide discovery via mass spectrometry and spectral networking

Quorum：通过质谱和光谱网络发现糖肽

• 批准号: 10011423
• 负责人: Anand Patel
• 金额: $ 14.68万
• 依托单位: DIGITAL PROTEOMICS LLC
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2021-05-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011423
• 关键词: Algorithms; Amino Acid Sequence Databases; Antibodies; Antigens; Basic Science; Benchmarking; CA-125 Antigen; Characteristics; Cleaved cell; Cloud Computing; Collection; Communities; Complex; Computer software; Data; Data Analyses; Data Set; Databases; Development; Diagnostic; Discipline; Discrimination; Disease; Disease Progression; Drug Kinetics; Engineering; Glycopeptides; Glycoproteins; Half-Life; Health; Human; Immunoglobulin G; Immunology; Ions; Knowledge; Libraries; Link; Malignant neoplasm of ovary; Mass Spectrum Analysis; Metadata; Methods; Modification; Monitor; Monoclonal Antibodies; Monosaccharides; Natural Immunity; Natural Products; Neoplasm Metastasis; Noise; Pathway Analysis; Peptides; Performance; Pharmacologic Substance; Phase; Play; Polysaccharides; Protein Analysis; Protein Glycosylation; Proteins; Proteome; Proteomics; Publications; Reporting; Research; Research Personnel; Role; Signal Transduction; Site; Small Business Innovation Research Grant; Software Tools; Structure; Technology; Therapeutic; Urine; Variant; adaptive immunity; analytical tool; assay development; base; cancer biomarkers; cloud platform; cluster computing; computerized tools; database structure; digital; glycoproteomics; glycosylation; improved; instrumentation; interest; macromolecule; malignant breast neoplasm; materials science; novel; pathogen; peptide I; protein phosphatase inhibitor-2; prototype; tandem mass spectrometry; therapeutic development; therapeutic protein; tool; translational impact; tumor

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.

糖基化是一种普遍的修饰，估计可修饰超过50％ 人类蛋白质是宿主 - 病原体相互作用的关键组成部分，自适应和 先天免疫和热发育。糖蛋白的计算工具 分析简化了有关可能聚糖结构的假设，从而限制了它们 在许多情况下实用程序。该建议旨在全面地描述 糖蛋白，包括新颖和意想不到的聚糖，具有数字蛋白质组学的法定蛋白 质谱数据分析软件，并启用进一步的糖蛋白 通过发现靶向抗体的开发来表征 糖肽。 Quorum软件建立在光谱网络范式上，该范式认为 结构相似的分子产生相似的质谱。在法定人数中用于糖肽 分析，网络光谱代表同一糖材上不同的聚糖结构 蛋白质。与传统的糖肽识别方法类似 将糖肽光谱与蛋白质序列数据库和聚糖结构匹配 数据库。与传统的方法不同，法定人员员工严格的虚假发现 基于靶标分析中的变异聚糖结构的速率计算。此外， 法定人数通过传播鉴定来提高糖肽的识别率 沿网络中的边缘，可以发现不在的聚糖结构 结构数据库，可能是完全新颖的。 法定人数将以糖蛋白标准为基准，表征良好 NIST单克隆抗体参考材料和总IgG，该抗体将建立一个 光谱网络变体糖肽发现的基线。法定软件是 部署到云中，作为我们可扩展的平台法定云的一部分，其中 糖蛋白分析是通用光谱网络分析的插件。应征测试人员 云平台的糖原，糖化分析中有应用 和治疗发展。