Powerful and interpretable control of false discoveries in two-group differential expression studies
Résumé
Motivation: The standard approach for statistical inference in differential expression (DE) analyses is
to control the False Discovery Rate (FDR). However, controlling the FDR does not in fact imply that
the proportion of false discoveries is upper bounded. Moreover, no statistical guarantee can be given
on subsets of genes selected by FDR thresholding. These known limitations are overcome by post hoc
inference, which provides guarantees of the number of proportion of false discoveries among arbitrary
gene selections. However, post hoc inference methods are not yet widely used for DE studies.
Results: In this paper, we demonstrate the relevance and illustrate the performance of adaptive
interpolation-based post hoc methods for two-group DE studies. First, we formalize the use of permutation-
based methods to obtain sharp confidence bounds that are adaptive to the dependence between genes.
Then, we introduce a generic linear time algorithm for computing post hoc bounds, making these bounds
applicable to large-scale two-group DE studies. The use of the resulting Adaptive Simes bound is illustrated
on a RNA sequencing study. Comprehensive numerical experiments based on real microarray and RNA
sequencing data demonstrate the statistical performance of the method.
Availability: A cross-platform open source implementation within the R package sanssouci is available at
https://sanssouci-org.github.io/sanssouci/.
Contact: pierre.neuvial@math.univ-toulouse.fr
Supplementary information: Supplementary data are available at Bioinformatics online. Rmarkdown
vignettes for the differential analysis of microarray and RNAseq data are available from the package.
Origine | Accord explicite pour ce dépôt |
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