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A Perspective on the Confident Comparison of Glycoprotein Site-Specific Glycosylation in Sample Cohorts.
Biochemistry ( IF 2.9 ) Pub Date : 2019-12-13 , DOI: 10.1021/acs.biochem.9b00730
Joshua A. Klein , Joseph Zaia

Protein glycosylation, resulting from glycosyl transferase reactions under complex control in the secretory pathway, consists of a distribution of related glycoforms at each glycosylation site. Because the biosynthetic substrate concentration and transport rates depend on architecture and other aspects of cellular phenotypes, site-specific glycosylation cannot be predicted accurately from genomic, transcriptomic, or proteomic information. Rather, it is necessary to quantify glycosylation at each protein site and how this changes among a sample cohort to provide information about disease mechanisms. At present, mature mass spectrometry-based methods allow for qualitative assignment of the glycan composition and glycosylation site of singly glycosylated proteolytic peptides. To make such quantitative comparisons, it is necessary to sample the glycosylation distribution with sufficient coverage and accuracy for confident assessment of the glycosylation changes that occur in the biological cohort. In this Perspective, we discuss the unmet needs for mass spectrometry acquisition methods and bioinformatics for the confident comparison of protein site-specific glycosylation among sample cohorts.

中文翻译:

对样本队列中糖蛋白位点特异性糖基化进行可信比较的观点。

由分泌途径中复杂控制下的糖基转移酶反应产生的蛋白质糖基化由每个糖基化位点的相关糖型分布组成。由于生物合成底物浓度和转运速率取决于细胞表型的结构和其他方面,因此无法根据基因组、转录组或蛋白质组信息准确预测位点特异性糖基化。相反,有必要量化每个蛋白质位点的糖基化以及它如何在样本群组中发生变化,以提供有关疾病机制的信息。目前,成熟的基于质谱的方法允许对单糖基化蛋白水解肽的聚糖组成和糖基化位点进行定性分配。为了进行这样的定量比较,有必要以足够的覆盖率和准确度对糖基化分布进行采样,以便对生物队列中发生的糖基化变化进行可靠评估。在这个观点中,我们讨论了质谱采集方法和生物信息学的未满足需求,以便在样本群组中可靠地比较蛋白质位点特异性糖基化。
更新日期:2019-12-13
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