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，估计修饰超过50%的 是宿主-病原体相互作用、适应性和 先天免疫和治疗发展。糖蛋白的计算工具 分析对可能的聚糖结构进行了简化假设，限制了其 在许多场景中的应用。该提案旨在全面描述 糖蛋白，包括新的和意想不到的聚糖，与数字蛋白质组学的Quorum 质谱数据分析软件，并使进一步的糖蛋白 通过开发针对发现的抗体进行表征 糖肽 Quorum软件建立在光谱网络范式的基础上，该范式假定， 结构相似的分子产生相似的质谱。在Quorum for Glycopeptide 分析，网络光谱表示相同糖位点上的不同聚糖结构 一种蛋白质。与传统的糖肽鉴定方法类似，Quorum 将糖肽光谱与蛋白质序列数据库和聚糖结构相匹配 数据库与传统方法不同，Quorum采用了严格的错误发现 在目标诱饵分析中基于变异聚糖结构的速率计算。此外，本发明还提供了一种方法， Quorum通过繁殖鉴定提高了糖肽的鉴定率 沿着网络中的边缘，使得能够发现不在网络中的聚糖结构。 结构数据库，并可能是完全新颖的。 Quorum将以糖蛋白标准品为基准，充分表征 NIST单克隆抗体参比物质和总IgG将建立 光谱网络变体糖肽发现的基线。Quorum软件是 作为我们可扩展平台Quorum Cloud的一部分， 糖蛋白分析是通用光谱网络分析的插件。入伍测试员 在糖工程，糖富集测定， 和治疗发展。