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Global FDR control across multiple RNAseq experiments.

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Hornburg, Milena 


MOTIVATION: While classical approaches for controlling the false discovery rate (FDR) of RNAseq experiments have been well described, modern research workflows and growing databases enable a new paradigm of controlling the FDR globally across RNAseq experiments in the past, present, and future. The simplest analysis strategy that analyses each RNAseq experiment separately and applies an FDR correction method can lead to inflation of the overall FDR. We propose applying recently developed methodology for online multiple hypothesis testing to control the global FDR in a principled way across multiple RNAseq experiments. RESULTS: We show that repeated application of classical repeated offline approaches has variable control of global FDR of RNAseq experiments over time. We demonstrate that the online FDR algorithms are a principled way to control FDR. Furthermore, in certain simulation scenarios, we observe empirically that online approaches have comparable power to repeated offline approaches. AVAILABILITY AND IMPLEMENTATION: The onlineFDR package is freely available at Additional code used for the simulation studies can be found at SUPPLEMENTARY INFORMATION: Supplementary Appendix is available in Bioinformatics online.


Acknowledgements: We would like to thank Eric Muise, Wendy Blumenschein, Doug Linn for their permission to use the real-world data as well as their comments and feedback. We would also like to thank Ola Olow and Uwe Mueller for their detailed comments and suggestions to improve this article. Finally, we thank the two anonymous reviewers for their helpful comments and suggestions.

Funder: Biometrika Trust

Funder: NHS

Funder: National Institute for Health Research or the Department of Health and Social Care


differential expression, false discovery rate, multiple hypothesis testing, RNAseq

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Oxford University Press (OUP)
Medical Research Council (MC_UU_00002/14)
National Institute for Health and Care Research (IS-BRC-1215-20014)