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Published on: January 31, 2017
A note on the false discovery rate and inconsistent comparisons between experiments
Roger Higdon1, Gerald van Belle, Eugene Kolker
1Seattle Children's Research Institute, Seattle, WA 98101, USA.
Motivation:
The false discovery rate (FDR) has been widely adopted to address the multiple comparisons issue in high-throughput experiments such as microarray gene-expression studies. However, while the FDR is quite useful as an approach to limit false discoveries within a single experiment, like other multiple comparison corrections it may be an inappropriate way to compare results across experiments. This article uses several examples based on gene-expression data to demonstrate the potential misinterpretations that can arise from using FDR to compare across experiments. Researchers should be aware of these pitfalls and wary of using FDR to compare experimental results. FDR should be augmented with other measures such as p-values and expression ratios. It is worth including standard error and variance information for meta-analyses and, if possible, the raw data for re-analyses. This is especially important for high-throughput studies because data are often re-used for different objectives, including comparing common elements across many experiments. No single error rate or data summary may be appropriate for all of the different objectives.
Insights
The false discovery rate (FDR) is useful within single experiments but can lead to misinterpretations when comparing results across studies. Augment FDR with p-values, expression ratios, and variance data for robust cross-experiment analysis.
Area of Science:
- Genomics
- Biostatistics
Background:
- The false discovery rate (FDR) is commonly used to manage multiple comparisons in high-throughput studies.
- While effective for single experiments, FDR may be inappropriate for comparing results across different studies.
Purpose of the Study:
- To demonstrate potential misinterpretations arising from using FDR to compare results across experiments.
- To highlight the need for caution when employing FDR for cross-experimental comparisons.
Main Methods:
- Utilized gene-expression data examples to illustrate potential pitfalls.
- Analyzed scenarios where FDR can lead to misinterpretations in comparative analyses.
Main Results:
- FDR-based comparisons across experiments can yield misleading conclusions.
- The study identified specific examples of misinterpretation using gene-expression data.
Conclusions:
- Researchers should be cautious when using FDR for comparing experimental results.
- Augment FDR with p-values, expression ratios, standard error, variance, and raw data for meta-analyses and re-analyses, especially in high-throughput studies.
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