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建立 N-聚糖生物标志物的综合生物标志物数据模型并实现其整合。

Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model.

机构信息

The Department of Biochemistry and Molecular Medicine, Ross Hall, School of Medicine & Health Sciences, The George Washington University, 2300 Eye Street N.W., Washington, DC 20037, USA.

The McCormick Genomic and Proteomic Center, The Department of Biochemistry and Molecular Medicine, Ross Hall, School of Medicine & Health Sciences, The George Washington University, 2300 Eye Street N.W., Washington, DC 20037, USA.

出版信息

Glycobiology. 2022 Sep 19;32(10):855-870. doi: 10.1093/glycob/cwac046.

Abstract

Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. Great interest exists in discovering early cancer biomarkers to improve outcomes. Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve the understanding and use of novel biomarkers such as glycans and glycoconjugates. Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. However, such data are distributed across publications and databases of diverse formats, which hamper their use in research and clinical application. Mass spectrometry measures of 50 N-glycans on 7 serum proteins in liver disease were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. Data provenance was documented with a standardized United States Food and Drug Administration-supported BioCompute Object. Using the biomarker data model allows the capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers; it can integrate N-glycan biomarker data with multi-source biomedical data and can foster discovery and insight within a unified data framework for glycan biomarker representation, thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/).

摘要

分子生物标志物可测量生物过程的离散成分,当这些成分受损时可能导致疾病。人们对发现早期癌症生物标志物以改善预后有着浓厚的兴趣。标准化数据模型中代表的生物标志物与多组学数据集成,可以提高对新型生物标志物(如聚糖和糖缀合物)的理解和应用。在肿瘤发生过程中改变的成分中,当与它们的蛋白质载体一起分析时,N-聚糖表现出相当大的生物标志物潜力。然而,这些数据分布在各种格式的出版物和数据库中,这阻碍了它们在研究和临床应用中的使用。对 50 种 N-聚糖在肝病 7 种血清蛋白上的质谱测量结果(作为一个面板)进行了整合,纳入癌症生物标志物数据模型,提供了唯一标识符、标准命名法、与聚糖资源的链接以及对标准蛋白质、基因、疾病和生物标志物信息的访问和本体论注释。使用标准化的美国食品和药物管理局支持的 BioCompute Object 记录了数据来源。使用生物标志物数据模型可以捕获更详细的信息,例如在肝硬化、肝细胞癌和移植组中丰度不同的聚糖。这种在标准化数据模型中的表示方式在统一框架中协调了糖组学数据,使糖蛋白生物标志物数据探索更容易为研究人员和其他数据资源所利用。我们描述的生物标志物数据模型可用于研究人员描述其新型聚糖和糖缀合物生物标志物;它可以将 N-聚糖生物标志物数据与多源生物医学数据集成,并在统一的数据框架内促进糖生物标志物表示的发现和洞察力,从而使数据可发现(Findable)、可访问(Accessible)、可互操作(Interoperable)、可重用(Reusable)(https://www.go-fair.org/fair-principles/)。

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