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Super-enhancers (SEs), as critical genomic regulatory elements driving high-level gene expression, play central roles in development,
cellular differentiation, and disease pathogenesis—particularly in oncology.
To address the growing need for comprehensive SE analysis across diverse biological contexts, we present
SEA VERSION 4.0
, an upgraded multi-omics database and analysis platform for super-enhancers.
Built upon our foundational work, SEA (Super-Enhancer Archive)—initially developed in 2015 and featured as a highlighted database in the 2020 issue of
Nucleic Acids Research—SEA VERSION 4.0 redefines the landscape of SE research by integrating cutting-edge data resources with advanced analytical tools,
empowering researchers worldwide to unravel SE-mediated gene regulation with unprecedented depth and efficiency.
SEA VERSION 4.0 marks a significant leap forward in data scale and diversity. Species coverage is expanded beyond model organisms to include three new additions: Rattus norvegicus (rat), Sus scrofa (pig), and Felis catus (cat). Cell line diversity is similarly enhanced, growing from 241 to 543 types, broadening the applicability of SE research across experimental systems. In SE identification, we incorporate H3K4me1 —an additional histone modification marker—alongside the established H3K27ac, BRD4, p300, and Med1, to improve detection accuracy. Leveraging publicly available ChIP-seq and CUT&TAG datasets, SEA VERSION 4.0 has mapped 496,071 super-enhancers and 29,584,078 enhancers, representing a 202% increase in SE detection compared to SEA3.0. This expanded dataset provides a robust foundation for exploring SE biology across tissues, cell types, and disease states.
SEA VERSION 4.0 transcends traditional database boundaries—it is not merely a repository, but a dynamic platform connecting data to biological discovery. Whether investigating fundamental SE mechanisms or translating findings to clinical applications, SEA VERSION 4.0 equips researchers with unparalleled data resources, analytical power, and visualization tools to decode SE’s central role in gene regulation and disease.
SEA VERSION 4.0 marks a significant leap forward in data scale and diversity. Species coverage is expanded beyond model organisms to include three new additions: Rattus norvegicus (rat), Sus scrofa (pig), and Felis catus (cat). Cell line diversity is similarly enhanced, growing from 241 to 543 types, broadening the applicability of SE research across experimental systems. In SE identification, we incorporate H3K4me1 —an additional histone modification marker—alongside the established H3K27ac, BRD4, p300, and Med1, to improve detection accuracy. Leveraging publicly available ChIP-seq and CUT&TAG datasets, SEA VERSION 4.0 has mapped 496,071 super-enhancers and 29,584,078 enhancers, representing a 202% increase in SE detection compared to SEA3.0. This expanded dataset provides a robust foundation for exploring SE biology across tissues, cell types, and disease states.
SEA VERSION 4.0 transcends traditional database boundaries—it is not merely a repository, but a dynamic platform connecting data to biological discovery. Whether investigating fundamental SE mechanisms or translating findings to clinical applications, SEA VERSION 4.0 equips researchers with unparalleled data resources, analytical power, and visualization tools to decode SE’s central role in gene regulation and disease.
SEA VERSION 4.0 reengineers the user experience to streamline SE analysis from data retrieval to functional interpretation:
-
Intelligent Search & Multi-Dimensional Annotation:
Users can query SEs or enhancers using core identifiers (e.g., genomic coordinates, associated genes) to retrieve customizable tables of annotations, including neighboring genes, recognition factors, and heterochromatin structural variations. Tables support single/multi-selection, with results exportable, convertible to BED files, or directly visualized.
-
Five Core Functional Modules:
Selected SEs unlock detailed analyses, including: (1) SE metadata (ID, location, associated genes, signal intensity, recognition factors); (2) visualization of SE regulatory networks; (3) GO/KEGG enrichment analysis of proximal genes; (4) transcription factor (TF) annotation; and (5) integration of regional heterochromatin structural variation data. These modules collectively decode SE-driven regulatory mechanisms.
- Specialized Analytical Tools: The "Analyze" module introduces SE-specific tools, notably the SE Region Specificity Analysis—a Shannon entropy-based method to identify cell type-, tissue-, or disease-specific SEs—providing critical insights into SE spatiotemporal regulation.
Visual Exploration Redefined: SEA Browser for Multi-Omics Integration
A cornerstone upgrade lies in the SEA Browser , reimagined to deliver intuitive, high-resolution visualization of SE regions.Supporting 14 species and up to 5,000 data tracks , the Browser enables users to inspect SE-proximal chromatin modifications, regulatory factors, chromatin structural components, genome annotations, epigenetic marks, and expression-chromatin interactions. This multi-omics visualization clarifies SE spatial organization and structural dynamics, guiding experimental design (e.g., CRISPR targeting) and fostering integrative data interpretation.
Tumor-Specific Insights: Unraveling SE Dynamics in Cancer
Recognizing SE’s role in driving tumorigenesis through cell-type-specific regulation, SEA VERSION 4.0 introduces the Tumor Specific Super-Enhancer tool.
By integrating tumor single-cell sequencing and ChIP-seq data, this tool identifies cell-type-specific SEs across 12 cancer types ,visualized via single-cell TSNE/UMAP plots and violin diagrams. This single-cell resolution approach uncovers SE signatures underlying tumor heterogeneity, offering novel targets for precision oncology.
A cornerstone upgrade lies in the SEA Browser , reimagined to deliver intuitive, high-resolution visualization of SE regions.Supporting 14 species and up to 5,000 data tracks , the Browser enables users to inspect SE-proximal chromatin modifications, regulatory factors, chromatin structural components, genome annotations, epigenetic marks, and expression-chromatin interactions. This multi-omics visualization clarifies SE spatial organization and structural dynamics, guiding experimental design (e.g., CRISPR targeting) and fostering integrative data interpretation.
Tumor-Specific Insights: Unraveling SE Dynamics in Cancer
Recognizing SE’s role in driving tumorigenesis through cell-type-specific regulation, SEA VERSION 4.0 introduces the Tumor Specific Super-Enhancer tool.
By integrating tumor single-cell sequencing and ChIP-seq data, this tool identifies cell-type-specific SEs across 12 cancer types ,visualized via single-cell TSNE/UMAP plots and violin diagrams. This single-cell resolution approach uncovers SE signatures underlying tumor heterogeneity, offering novel targets for precision oncology.
News & Updates
Species Expansion
SEA 4.0 includes data from three newly added species: Rattus norvegicus, Sus scrofa, and Felis catus.
Recognition Factors
On the basis of H3k27ac, p300, BRD4, and Med1 ChIP-seq data, SEA 4.0 also recognized enahncers and super-enhancers from data of H3K4me1 in six species.
Analysis Module Update
SEA 4.0 introduces several major enhancements about analysis module:
1.The enrichment analysis module now supports GO/KEGG analysis for 9 species.
2.The SE specificity analysis incorporates H3K4me1 in addition to H3K27ac.
3.The algorithm has been optimized by integrating peak intensity with effective length proportion for a more biologically meaningful metric.
4.SEA 4.0 includes human heterochromatin region data from HHCDB and displays overlaps with SEs in both the analysis and search modules.
Tools Update
SEA 4.0 provides a comprehensive analysis of super-enhancer (SE) regulatory networks, including associated enhancers, genes, and transcription factors. Besides that, SEA 4.0 identifies cell subpopulations from scRNA-seq data and defines tumor-type-specific SEs as those located near marker genes, then evaluates the expression of these marker genes across different subpopulations.
SEA Browser Update
SEA 4.0 have categorized and organized all the tracks in the SEA Browser to make it easier and more convenient for users to access and use them. Additionally, SEA 4.0 added "Heterochromatin Region" track types to show chromatin interactions in the target area.
Home page statistics Update
SEA 4.0 have visualized the data update and updated the super enhancer identification method in home page.
SEA 4.0 includes data from three newly added species: Rattus norvegicus, Sus scrofa, and Felis catus.
Recognition Factors
On the basis of H3k27ac, p300, BRD4, and Med1 ChIP-seq data, SEA 4.0 also recognized enahncers and super-enhancers from data of H3K4me1 in six species.
Analysis Module Update
SEA 4.0 introduces several major enhancements about analysis module:
1.The enrichment analysis module now supports GO/KEGG analysis for 9 species.
2.The SE specificity analysis incorporates H3K4me1 in addition to H3K27ac.
3.The algorithm has been optimized by integrating peak intensity with effective length proportion for a more biologically meaningful metric.
4.SEA 4.0 includes human heterochromatin region data from HHCDB and displays overlaps with SEs in both the analysis and search modules.
Tools Update
SEA 4.0 provides a comprehensive analysis of super-enhancer (SE) regulatory networks, including associated enhancers, genes, and transcription factors. Besides that, SEA 4.0 identifies cell subpopulations from scRNA-seq data and defines tumor-type-specific SEs as those located near marker genes, then evaluates the expression of these marker genes across different subpopulations.
SEA Browser Update
SEA 4.0 have categorized and organized all the tracks in the SEA Browser to make it easier and more convenient for users to access and use them. Additionally, SEA 4.0 added "Heterochromatin Region" track types to show chromatin interactions in the target area.
Home page statistics Update
SEA 4.0 have visualized the data update and updated the super enhancer identification method in home page.
