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The optimal discovery procedure for significance analysis of general gene expression studies

View ORCID ProfileAndrew J. Bass, View ORCID ProfileJohn D. Storey
doi: https://doi.org/10.1101/571992
Andrew J. Bass
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544 USA
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John D. Storey
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544 USA
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  • For correspondence: jstorey@princeton.edu
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Abstract

Analysis of biological data often involves the simultaneous testing of thousands of genes. This requires two key steps: the ranking of genes and the selection of important genes based on a significance threshold. One such testing procedure, called the ‘optimal discovery procedure’ (ODP), leverages information across different tests to provide an optimal ranking of genes. This approach can lead to substantial improvements in statistical power compared to other methods. However, current applications of the ODP have only been established for simple study designs using microarray technology. Here we extend this work to the analysis of complex study designs and RNA sequencing studies. We then apply our extended framework to a static RNA sequencing study, a longitudinal and an independent sampling time-series study, and an independent sampling dose-response study. We find that our method shows improved performance compared to other testing procedures, finding more differentially expressed genes and increasing power for enrichment analysis. Thus the extended ODP enables a superior significance analysis of genomic studies. The algorithm is implemented in our freely available R package called edge.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted March 27, 2019.
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The optimal discovery procedure for significance analysis of general gene expression studies
Andrew J. Bass, John D. Storey
bioRxiv 571992; doi: https://doi.org/10.1101/571992
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The optimal discovery procedure for significance analysis of general gene expression studies
Andrew J. Bass, John D. Storey
bioRxiv 571992; doi: https://doi.org/10.1101/571992

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