ChEA3: Transcription Factor Enrichment Analysis

Transcription factors (TFs) are proteins that control gene expression by binding and unbinding near coding regions to regulate the transcriptional machinery. TF enrichment analysis (TFEA) prioritizes transcription factors based the overlap between given lists of differentially expressed genes, and previously annotated TF targets assembled from multiple resources. Hence, TFEA can aid in identifying the TFs responsible for observed changes in gene expression when comparing control and perturbation samples. In the past, we have developed and published ChEA and ChEA2 which are ChIP-seq enrichment analysis tools made of gene set libraries created from published ChIP-seq data extracted from multiple sources. ChEA3 builds upon these prior versions of ChEA by including more libraries, adding benchmarks, and cross library analyses. For ChEA3 the following TF-target gene set libraries were assembled: Putative targets as determined by ChIP-seq experiments from ENCODE and individual publications; co-expression of TFs with other genes based on processed RNA-seq from GTEx and ARCHS4; co-occurrence of TFs with other genes by examining thousands of gene lists submitted to the tool Enrichr; protein-protein interactions involving direct interactions with TFs; and gene signatures resulting from single TF perturbations followed by genome-wide gene expression experiments. ChEA3 is delivered as a web-based application that performs TFEA for each TF library individually, and also by integrating the results across all libraries. Using various benchmarks, we found that integrating libraries boosts performance of ranking TF correctly. The ChEA3 web portal application front-end was developed with Mobirise, while the back-end was implemented as two R packages hosted on an OpenCPU server to enable integration via an API. The ChEA3 web application features interactive visualization of a global mammalian TF-TF regulatory network, in which enriched TFs are highlighted as nodes in the network. Interactive heatmaps visualize inter- and cross-library TF modules to enable users to explore the data within the ChEA3 TF libraries. Overall, since ChEA3 is an enhanced version of the ChEA project, it is expected to guide many future experimental studies that aim to explore regulatory mechanisms in mammalian cells.

[@ProfGregTuckerKellogg]

Very nice. Were the Enrichr results shown at 0:40 using the same 501 input genes as the integrated ChEA3 results at 4:10?

[@MamaYouBeenOnMyMind]

Thank you for your question! Yes, the input gene sets to Enrichr and ChEA3 in this example were the same.