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High throughput human plasma N -glycan analysis using DNA analyzer and multivariate analysis for biomarker discovery
Analytica Chimica Acta ( IF 5.7 ) Pub Date : 2017-12-01 , DOI: 10.1016/j.aca.2017.09.003
Hua-tao Feng , Siying Lim , Anna Karen Carrasco Laserna , Pingjing Li , Xuejiao Yin , Erhan Simsek , Shaheer H. Khan , Shiaw-Min Chen , Sam F.Y. Li

Carbohydrates form the majority of organic compounds found in nature and their presence on proteins influences many important bioactivities. Therefore, glycan profiling shows potential in clinical applications. This work demonstrates the use of a high-throughput GlycanAssure™ sample preparation technology and multi-capillary DNA analyzer for the analysis of the major N-linked glycans (N-glycans) found in human plasma. The application involves two biomarker studies: (1) in profiling patients with chronic kidney disease and (2) in differentiating heart disease patients with normal controls in response to an antiplatelet drug from hypo-responders. Due to complexity of the study data, bio-statistical methods were applied to data processing. 37 N-glycan peaks were observed from separation results, with confirmed structure for most glycans. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to build models to differentiate the patient groups. The percentages of correct classification of the models reached 95.45% for the chronic kidney disease dataset and 85.42% for the anti-platelet drug response dataset. Given that blood N-glycan profiles had been shown to reflect certain disease states, this high-throughput platform could potentially be used for the simultaneous screening of multiple glycan biomarkers, with as little as one drop of blood sample.

中文翻译:

使用 DNA 分析仪和多变量分析进行高通量人血浆 N-聚糖分析以发现生物标志物

碳水化合物构成自然界中发现的大多数有机化合物,它们在蛋白质中的存在会影响许多重要的生物活性。因此,聚糖分析在临床应用中显示出潜力。这项工作展示了使用高通量 GlycanAssure™ 样品制备技术和多毛细管 DNA 分析仪来分析人血浆中发现的主要 N-连接聚糖 (N-聚糖)。该应用程序涉及两项生物标志物研究:(1) 对慢性肾病患者进行分析,以及 (2) 区分心脏病患者与正常对照者对来自低反应者的抗血小板药物的反应。由于研究数据的复杂性,采用生物统计方法进行数据处理。从分离结果中观察到 37 个 N-聚糖峰,大多数聚糖的结构得到确认。使用主成分分析 (PCA) 和正交偏最小二乘判别分析 (OPLS-DA) 建立模型以区分患者组。模型正确分类的百分比在慢性肾病数据集上达到了 95.45%,在抗血小板药物反应数据集上达到了 85.42%。鉴于血液 N-聚糖谱已被证明可以反映某些疾病状态,这种高通量平台有可能用于同时筛选多种聚糖生物标志物,只需一滴血样。42% 用于抗血小板药物反应数据集。鉴于血液 N-聚糖谱已被证明可以反映某些疾病状态,这种高通量平台有可能用于同时筛选多种聚糖生物标志物,只需一滴血样。42% 用于抗血小板药物反应数据集。鉴于血液 N-聚糖谱已被证明可以反映某些疾病状态,这种高通量平台有可能用于同时筛选多种聚糖生物标志物,只需一滴血样。
更新日期:2017-12-01
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