RT Journal Article SR Electronic T1 EmpiReS: Differential Analysis of Gene Expression and Alternative Splicing JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.08.23.234237 DO 10.1101/2020.08.23.234237 A1 Gergely Csaba A1 Evi Berchtold A1 Armin Hadziahmetovic A1 Markus Gruber A1 Constantin Ammar A1 Ralf Zimmer YR 2020 UL http://biorxiv.org/content/early/2020/08/24/2020.08.23.234237.abstract AB While absolute quantification is challenging in high-throughput measurements, changes of features between conditions can often be determined with high precision. Therefore, analysis of fold changes is the standard method, but often, a doubly differential analysis of changes of changes is required. Differential alternative splicing is an example of a doubly differential analysis, i.e. fold changes between conditions for different isoforms of a gene. EmpiRe is a quantitative approach for various kinds of omics data based on fold changes for appropriate features of biological objects. Empirical error distributions for these fold changes are estimated from Replicate measurements and used to quantify feature fold changes and their directions. We assess the performance of EmpiRe to detect differentially expressed genes applied to RNA-Seq using simulated data. It achieved higher precision than established tools at nearly the same recall level. Furthermore, we assess the detection of alternatively Spliced genes via changes of isoform fold changes (EmpiReS) on distribution-free simulations and experimentally validated splicing events. EmpiReS achieves the best precision-recall values for simulations based on different biological datasets. We propose EmpiRe(S) as a general, quantitative and fast approach with high reliability and an excellent trade-off between sensitivity and precision in (doubly) differential analyses.Competing Interest StatementThe authors have declared no competing interest.