Assessment of Variability in the SOMAscan Assay.

Assessment of Variability in the SOMAscan Assay.
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DOI:
10.1038/s41598-017-14755-5
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发表时间:
2017-10-27
期刊:
影响因子:
4.6
通讯作者:
Biancotto A
Biancotto A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Candia J;Cheung F;Kotliarov Y;Fantoni G;Sellers B;Griesman T;Huang J;Stuccio S;Zingone A;Ryan BM;Tsang JS;Biancotto A

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SOMAscan是一种基于适体的蛋白质组学分析方法,能够以高灵敏度和特异性测量血清、血浆和其他生物基质中的1,305种人类蛋白质分析物。在这项工作中,我们提出了一个全面的荟萃分析的性能的基础上,多个血清和血浆运行使用当前的1.3 k检测,以及以前的1.1 k版本。我们讨论规范化程序,并检查不同的策略,以尽量减少板内和板间滋扰的影响。我们实施了基于校准品样本的荟萃分析,以表征每种蛋白质分析物的变异系数和信号背景强度。通过将变异系数估计纳入统计变异性的理论模型,我们还提供了一个框架,使干预研究和临床试验中的重要性进行严格的统计检验,以及实验室内和实验室间的质量控制。此外,我们调查了健康受试者基线的稳定性,并确定了一组分析物,这些分析物在考虑了技术可变性后表现出生物稳定的基线。这项工作是伴随着一个互动的基于网络的工具,一个倡议,有可能成为一个定期更新的基石,高质量的存储库与数据共享,再现性和可重复使用的最终目标。
SOMAscan is an aptamer-based proteomics assay capable of measuring 1,305 human protein analytes in serum, plasma, and other biological matrices with high sensitivity and specificity. In this work, we present a comprehensive meta-analysis of performance based on multiple serum and plasma runs using the current 1.3 k assay, as well as the previous 1.1 k version. We discuss normalization procedures and examine different strategies to minimize intra- and interplate nuisance effects. We implement a meta-analysis based on calibrator samples to characterize the coefficient of variation and signal-over-background intensity of each protein analyte. By incorporating coefficient of variation estimates into a theoretical model of statistical variability, we also provide a framework to enable rigorous statistical tests of significance in intervention studies and clinical trials, as well as quality control within and across laboratories. Furthermore, we investigate the stability of healthy subject baselines and determine the set of analytes that exhibit biologically stable baselines after technical variability is factored in. This work is accompanied by an interactive web-based tool, an initiative with the potential to become the cornerstone of a regularly updated, high quality repository with data sharing, reproducibility, and reusability as ultimate goals.
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