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

Area of Science:

• Genomics
• Epigenetics
• Computational Biology

Background:

• Super-enhancers (SEs) are critical epigenetic regulators influencing cellular identity and disease pathogenesis.
• Understanding SEs requires comprehensive, cross-species analysis of their genomic context and regulatory functions.

Purpose of the Study:

• To present SEA version 4.0, an updated systematic platform for identifying and analyzing SEs.
• To elucidate the roles of SEs in development and disease through advanced computational tools.

Main Methods:

• A uniform computational pipeline was developed to identify SEs using five key histone marks (H3K27ac, BRD4, p300, Med1, H3K4me1) across 14 species.
• SEA version 4.0 integrates genome annotations, functional enrichment analysis, a Shannon entropy-based algorithm for specific SE identification, and an interactive regulatory network.
• A cell-specific SE detector was developed using scRNA-seq data for cancer research.

Main Results:

• The database now stores 496,071 SEs and 29,584,078 enhancers.
• SEA version 4.0 provides extensive annotations, functional enrichment, and interactive networks for human and mouse.
• Cell-type-specific SEs in cancer were explored using scRNA-seq data.

Conclusions:

• SEA version 4.0 is an indispensable resource for decoding SE mechanisms in development and disease.
• The platform facilitates genomic and cross-species comparisons, revealing complex genomic interactions.
• SEA version 4.0 offers powerful visualization and interaction capabilities for SE research.