DENdb: database of integrated human enhancers

Abstract

Enhancers are cis-acting DNA regulatory regions that play a key role in distal control of transcriptional activities. Identification of enhancers, coupled with a comprehensive functional analysis of their properties, could improve our understanding of complex gene transcription mechanisms and gene regulation processes in general. We developed DENdb, a centralized on-line repository of predicted enhancers derived from multiple human cell-lines. DENdb integrates enhancers predicted by five different methods generating an enriched catalogue of putative enhancers for each of the analysed cell-lines. DENdb provides information about the overlap of enhancers with DNase I hypersensitive regions, ChIP-seq regions of a number of transcription factors and transcription factor binding motifs, means to explore enhancer interactions with DNA using several chromatin interaction assays and enhancer neighbouring genes. DENdb is designed as a relational database that facilitates fast and efficient searching, browsing and visualization of information. Database URL: http://www.cbrc.kaust.edu.sa/dendb/.

Figure 1.

DENdb’s implementation employs the three-tier architecture approach. This includes data, logic and presentation tiers.

Figure 2.

Statistics for H1hesc cell-line enhancers. (a) Bar plot represents genome coverage in million base pairs by each method individually. (b) Venn diagrams show the pairwise intersection between the predictions of five tools used in DENdb. Size of the circle represents relative proportion of predictions for a method compared to the union of both methods.

Figure 3.

Snapshot of DENdb. An example of querying enhancers that overlap with DHS regions. Queried enhancers are from GM12878 cell-line and from chromosome 4. The query example specifies enhancers having support of 4 or 5 only and being predicted by CSI-ANN and ENCODE ChromHMM. After step 1, results appear in a tabular format. Step 2 shows exploring details of a specific enhancer. Step 3 shows visualizing enhancers in current page in genome browser.