RegEnrich gene regulator enrichment analysis reveals a key role of the ETS transcription factor family in interferon signaling

Changes in a few key transcriptional regulators can lead to different biological states. Extracting the key gene regulators governing a biological state allows us to gain mechanistic insights. Most current tools perform pathway/GO enrichment analysis to identify key genes and regulators but tend to overlook the gene/protein regulatory interactions. Here we present RegEnrich, an open-source Bioconductor R package, which combines differential expression analysis, data-driven gene regulatory network inference, enrichment analysis, and gene regulator ranking to identify key regulators using gene/protein expression profiling data. By benchmarking using multiple gene expression datasets of gene silencing studies, we found that RegEnrich using the GSEA method to rank the regulators performed the best. Further, RegEnrich was applied to 21 publicly available datasets on in vitro interferon-stimulation of different cell types. Collectively, RegEnrich can accurately identify key gene regulators from the cells under different biological states, which can be valuable in mechanistically studying cell differentiation, cell response to drug stimulation, disease development, and ultimately drug development. Weiyang Tao et al. describe RegEnrich, an R package capable of conducting several analyses to identify transcriptional regulators driving gene expression signatures. As an example, they apply RegEnrich to dozens of in vitro gene expression datasets to identify that several ETS transcription factor family members are associated with interferon stimulation.

Automated summary

RegEnrich is an open-source Bioconductor R package that can identify transcriptional regulators driving gene expression signatures through multiple analysis methods. This tool has important implications in mechanistically studying cell differentiation, cell response to drug stimulation, disease development, and drug development.