SEA version 4.0: a major expansion and update of the Super-Enhancer Archive

Abstract Super-enhancers (SEs) are pivotal epigenetic regulatory elements that profoundly influence cell fate and disease. We herein present an updated SEA version 4.0, a systematic platform designed to elucidate the roles of SEs. A uniform computational pipeline was established to identify SEs based on five key histone marks, using H3K27ac, BRD4, p300, Med1, and the newly added H3K4me1, across 14 species. 496 071 SEs and 29 584 078 enhancers have been stored in the database. It provides extensive genome annotations, including nearby genes, transcription factor binding sites, chromatin accessibility, and other gene regulation signatures. SEA version 4.0 has also achieved functional enrichment analysis of SEs. And a Shannon entropy-based algorithm is employed to identify specific SEs. Furthermore, SEA version 4.0 introduces an interactive regulatory network that incorporates SEs, enhancers, transcription factors, and proximal genes for human and mouse. Additionally, a cell-specific SE detector is provided, designed for cancer research by leveraging scRNA-seq data from 12 cancer and normal samples to explore cell-type-specific SEs. The performance interaction and visualization of SEA version 4.0 enable genomic and cross-species comparisons, revealing complex genomic interactions and becoming an indispensable resource for decoding the mechanisms of SE in development and disease. Access freely at http://sea4.edbc.org.