Improved Glycoinformatics Tools for the Interpretation of Sequential Mass Spectra

用于解释序列质谱的改进的糖信息学工具

• 批准号: 7672010
• 负责人: DAVID ASHLINE
• 金额: $ 12万
• 依托单位: GLYCOME TECHNOLOGIES, INC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2010-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672010
• 关键词: Affect; Algorithms; Area; Biological; Biological Markers; Biomedical Research; Butter; Carbohydrates; Collection; Columbidae; Computer software; Congenital Disorders; Detection; Development; Disease; Ensure; European; Fertilization; Funding; Glycoproteins; Goals; Housing; Ions; Isomerism; Link; Lipids; Malignant Neoplasms; Mannose; Manuscripts; Mass Spectrum Analysis; Metabolism; Methods; Microbe; Monitor; Monosaccharides; Mus; Parasites; Pattern; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Play; Polysaccharides; Proteins; Publications; Request for Proposals; Research; Research Design; Role; Sampling; Sandhoff Disease; Series; Services; Software Validation; Source Code; Structure; Technology; Testing; Therapeutic; Time; Uncertainty; United States; Vaccines; Work; base; commercial application; cost; data acquisition; data sharing; design; drug discovery; egg; experience; glycosylation; improved; insight; instrument; man; mass spectrometer; protein folding; protein function; public health relevance; ribonuclease B; software development; technological innovation; therapeutic development; tool

DESCRIPTION (provided by applicant): Glycans (carbohydrates) can covalently attach to, and affect the function of, proteins and lipids. Understanding and modifying the glycan components of a glycoprotein are key steps toward the development and refinement of many therapeutic drugs. Glycans are also significant in a number of biological and biomedical research areas. For instance, glycans are biomarkers for various cancers, the principal component of new and promising vaccines, and drive parasite-host and microbe-host interactions, as well as egg fertilization, protein folding, and more. Defective glycan assembly or metabolism manifests itself as Congenital Disorders of Glycosylation, Gaucher, Fabry, Tay-Sachs, and Sandhoff diseases, among others. Research in these and related areas is hindered by the lack of effective glycan sequencing tools and methods. Currently, there are no commercially-available comprehensive analytical strategies to determine glycan structures. Glycome Technologies Inc. (GT) is a newly-formed commercial venture whose goal is to provide glycoanalytic services to pharmaceutical companies. To assist in performing these analyses, we are developing a series of proprietary glycoinformatics tools to enable efficient glycan analysis via sequential mass spectrometry (MSn). This collection of tools is known as gtSuite(tm). GT is requesting funding to support the development of two software components: (1) gtAnnotate(tm), used for MSn spectrum annotation and viewing, and (2) gtIsoDetect(tm), used to detect the presence of structural isomers (glycans which contain the same monosaccharide residues, but linked in different ways to form distinct structures). Analysis of glycan structures via MSn is a currently labor-intensive task suitable only for experts. However, bolstered by the enhanced capabilities of a mature gtSuite, Glycome Technologies will be able to offer cost-effective glycoanalytic services, including detailed glycan structural analysis and monitoring of the batch-to-batch glycosylation patterns of glycoprotein therapeutics. PUBLIC HEALTH RELEVANCE: The enhanced glycan analysis capabilities afforded by a mature gtSuite(tm) glycoinformatics platform will accelerate the pace of glycoprotein therapeutic development (Dove 14; Koeller and Wong 45; Walsh 84). It will also provide insights into a number of biological and biomedical research areas where glycans play a significant role, including cancer biomarker discovery (Alper 2; Dziadek and Kunz 17; Ono and Hakomori 59; Turner 76); vaccine discovery (Ada and Isaacs 1; Dwek 16; Gaucher 22; Lo- Man 53; Muhlecker 57); parasite-host and microbe-host interactions (Hokke and Deedler 36; Khoo and Dell 44; Nyame 58); and diseases such as Congenital Disorders of Glycosylation, Gaucher, Fabry, Tay-Sachs, and Sandhoff (Butters 8; Dwek 16; Jaeken and Matthijs 40; Jeyakumar 41; Platt 61; Vosseller 82). Research in these and related areas is hindered by the lack of effective glycan sequencing tools and methods (Stephan 73), and will benefit from the software proposed here.

描述（由申请人提供）：聚糖（碳水化合物）可以共价附着并影响蛋白质和脂质的功能。了解和修饰糖蛋白的聚糖成分是迈向许多治疗药物的开发和完善的关键步骤。聚糖在许多生物学和生物医学研究领域也很重要。例如，聚糖是各种癌症的生物标志物，新的和有前途的疫苗的主要成分，驱动寄生虫宿主和微生物 - 宿主相互作用，以及鸡蛋受精，蛋白质折叠等。有缺陷的聚糖组装或新陈代谢表现为糖基化，高雪剂，法布里，Tay-Sachs和Sandhoff疾病的先天性疾病。缺乏有效的聚糖测序工具和方法，阻碍了这些和相关领域的研究。当前，尚无商业化的综合分析策略来确定聚糖结构。 Glycome Technologies Inc.（GT）是一家新成型的商业企业，其目标是为制药公司提供糖分析服务。为了协助执行这些分析，我们正在开发一系列专有的糖化工具，以通过顺序质谱（MSN）来实现有效的聚糖分析。该工具的集合被称为GTSUITE（TM）。 GT要求资金支持两个软件组件的开发：（1）用于MSN频谱注释和观看的Gtannotate（TM），以及（2）Gtisodetect（TM），用于检测结构异构体的存在（Glycans（Glycans）（Glycans）（Glycans（Glycans），包含相同的Monosacachield Chare carone consemente consemantues consemachield Chare consemantues consementues nistery inters inters inters inters inters inters inters inters inters inters inters inters interne colducties）。通过MSN对聚糖结构进行分析是目前仅适用于专家的劳动密集型任务。然而，受到成熟GTSuite的增强功能的支持，Glycome Technologies将能够提供具有成本效益的甘氨酸分析服务，包括详细的Glycan结构分析以及对糖蛋白疗法的批处理糖基化模式的监测。公共卫生相关性：成熟的GTSuite（TM）糖胶形式平台提供的增强的聚糖分析能力将加速糖蛋白治疗性开发的速度（Dove 14; Koeller and Wong 45; Walsh 84）。它还将提供有关聚糖发挥重要作用的许多生物学和生物医学研究领域的见解，包括癌症生物标志物发现（Alper 2； Dziadek和Kunz 17； Ono和Hakomori 59； Turner 76）；疫苗发现（ADA和ISAACS 1; DWEK 16; GAUCHER 22; LO-LOMAN 53; MUHLECKER 57）;寄生虫 - 主持人和微生物 - 宿主相互作用（Hokke和Deedler 36; Khoo and Dell 44; Nyame 58）;以及诸如糖基化的先天性疾病，高雪剂，法布里，Tay-Sachs和Sandhoff（Butters 8; Dwek 16; Dwek 16; Jaeken and Matthijs 40; Jeyakumar 41; Platt 61; Platt 61; Vosseller 82）。缺乏有效的聚糖测序工具和方法（Stephan 73），在这些和相关领域的研究受到了阻碍，并且将从此处提出的软件中受益。