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A note on statistical repeatability and study design for high‐throughput assays

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 p...

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Detalles Bibliográficos
Autores principales: Nicholson, George, Holmes, Chris
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299465/
https://www.ncbi.nlm.nih.gov/pubmed/27882571
http://dx.doi.org/10.1002/sim.7175
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author Nicholson, George
Holmes, Chris
author_facet Nicholson, George
Holmes, Chris
author_sort Nicholson, George
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description 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.
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spelling pubmed-52994652017-02-22 A note on statistical repeatability and study design for high‐throughput assays Nicholson, George Holmes, Chris Stat Med Research Articles 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. John Wiley & Sons, Ltd 2016-11-24 2017-02-28 /pmc/articles/PMC5299465/ /pubmed/27882571 http://dx.doi.org/10.1002/sim.7175 Text en © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Nicholson, George
Holmes, Chris
A note on statistical repeatability and study design for high‐throughput assays
title A note on statistical repeatability and study design for high‐throughput assays
title_full A note on statistical repeatability and study design for high‐throughput assays
title_fullStr A note on statistical repeatability and study design for high‐throughput assays
title_full_unstemmed A note on statistical repeatability and study design for high‐throughput assays
title_short A note on statistical repeatability and study design for high‐throughput assays
title_sort note on statistical repeatability and study design for high‐throughput assays
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5299465/
https://www.ncbi.nlm.nih.gov/pubmed/27882571
http://dx.doi.org/10.1002/sim.7175
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