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

TitleThe optimal discovery procedure for significance analysis of general gene expression studies.
Publication TypeJournal Article
Year of Publication2021
AuthorsBass, AJ, Storey, JD
JournalBioinformatics
Volume37
Issue3
Pagination367-374
Date Published2021 04 20
ISSN1367-4811
KeywordsAlgorithms, Gene Expression, Longitudinal Studies, Sequence Analysis, RNA, Software
Abstract

<p><b>MOTIVATION: </b>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.</p><p><b>RESULTS: </b>We apply our extended framework to a static RNA-sequencing study, a longitudinal study, an independent sampling time-series study,and an independent sampling dose-response study. 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 favorable significance analysis of genome-wide gene expression studies.</p><p><b>AVAILABILITY AND IMPLEMENTATION: </b>The algorithm is implemented in our freely available R package called edge and can be downloaded at https://www.bioconductor.org/packages/release/bioc/html/edge.html.</p><p... INFORMATION: </b>Supplementary data are available at Bioinformatics online.</p>

DOI10.1093/bioinformatics/btaa707
Alternate JournalBioinformatics
PubMed ID32818252
PubMed Central IDPMC8058779
Grant ListT32 HG003284 / HG / NHGRI NIH HHS / United States
R01 HG006448 / HG / NHGRI NIH HHS / United States