Nicholson George, Holmes Chris
Department of Statistics, University of Oxford, 24-29 St Giles, Oxford, OX1 3LB, U.K.
Stat Med. 2017 Feb 28;36(5):790-798. doi: 10.1002/sim.7175. Epub 2016 Nov 24.
Characterizing the technical precision of measurements is a necessary stage in the planning of experiments and in the formal sample size calculation for optimal design. Instruments that measure multiple analytes simultaneously, such as in high-throughput assays arising in biomedical research, pose particular challenges from a statistical perspective. The current most popular method for assessing precision of high-throughput assays is by scatterplotting data from technical replicates. Here, we question the statistical rationale of this approach from both an empirical and theoretical perspective, illustrating our discussion using four example data sets from different genomic platforms. We demonstrate that such scatterplots convey little statistical information of relevance and are potentially highly misleading. We present an alternative framework for assessing the precision of high-throughput assays and planning biomedical experiments. Our methods are based on repeatability-a long-established statistical quantity also known as the intraclass correlation coefficient. We provide guidance and software for estimation and visualization of repeatability of high-throughput assays, and for its incorporation into study design. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
表征测量的技术精度是实验规划以及进行最优设计的正式样本量计算的必要阶段。同时测量多种分析物的仪器,比如生物医学研究中出现的高通量检测,从统计学角度来看会带来特殊挑战。当前评估高通量检测精度最流行的方法是绘制技术重复数据的散点图。在此,我们从实证和理论角度质疑这种方法的统计学原理,并使用来自不同基因组平台的四个示例数据集来说明我们的讨论。我们证明此类散点图几乎没有传达相关的统计信息,并且可能极具误导性。我们提出了一个用于评估高通量检测精度和规划生物医学实验的替代框架。我们的方法基于重复性——一个早已确立的统计量,也称为组内相关系数。我们提供了用于估计和可视化高通量检测重复性以及将其纳入研究设计的指导和软件。© 2016作者。《医学统计学》由约翰·威利父子有限公司出版。