Ensembl regulation resources

Abstract

New experimental techniques in epigenomics allow researchers to assay a diversity of highly dynamic features such as histone marks, DNA modifications or chromatin structure. The study of their fluctuations should provide insights into gene expression regulation, cell differentiation and disease. The Ensembl project collects and maintains the Ensembl regulation data resources on epigenetic marks, transcription factor binding and DNA methylation for human and mouse, as well as microarray probe mappings and annotations for a variety of chordate genomes. From this data, we produce a functional annotation of the regulatory elements along the human and mouse genomes with plans to expand to other species as data becomes available. Starting from well-studied cell lines, we will progressively expand our library of measurements to a greater variety of samples. Ensembl's regulation resources provide a central and easy-to-query repository for reference epigenomes. As with all Ensembl data, it is freely available at http://www.ensembl.org, from the Perl and REST APIs and from the public Ensembl MySQL database server at ensembldb.ensembl.org. Database URL: http://www.ensembl.org.

Figure 1.

Regulation tracks. Screenshot of the ‘Region in detail’ location view, upstream of the human TP53 gene. The default ‘MultiCell’ regulatory features track is shown. Below, the regulatory features, segmentation, ‘TFBS & DNase1’ and ‘Histones and Polymerases’ tracks associated to cell type GM12878. Finally, below again, the regulatory features annotated with activity for a few other cell types. Features that are inactive in a specific cell type are greyed out. Various elements were clicked to reveal floating menus with feature specific data and links to detailed views or external resources.

Figure 2.

Modelling bisulphite sequencing results with a Bayesian model. The fraction of converted reads in bisulphite sequencing is correlated to the methylation status of the underlying DNA. We show here a Bayesian model that fits the observed data by dividing the cytosines into three categories: methylated (red), unmethylated (blue) and unknown (green).

Figure 3.

Configuration panel and data selection matrix. This panel is available via the ‘Configure this page’ button in the location view. The ‘Regulation’ menu items describe the different types of data available. Lower down, the ‘Oligo Probes’ menu items provides access to microarray probe mappings. The ‘Open chromatin & TFBS’ item has been selected to reveal a configuration matrix. To assist first time users, a tutorial is presented, this tutorial can be hidden or shown as desired.

Figure 4.

Regulatory Feature ‘Summary’ view. This view displays the genes overlapped by the regulatory element of interest, along with activity information in all available cell types. In this case, the red promoter is constitutively active, but the nearby cyan CTCF binding site is active in only 4 cell types.

Figure 5.

Regulatory feature ‘Details by cell line’ view. This view displays all the evidence surrounding a regulatory feature of interest, either as regions (ChIP-seq peaks) or signal functions. At the top, a solid multicolored bar represents the segmentation for the desired cell types. Note the selector buttons above the window.

Figure 6.

Regulatory Feature ‘Details by cell line’, cell type and experimental evidence selectors. (A) At the top of the ‘Details by cell line view’ (Figure 5) a button labelled ‘Select cells’ displays this modal window, which allows the user to quickly toggle cell types on or off. (B) Similarly, the ‘Select evidence’ button displays this modal window, which allows the user to quickly toggle experimental tracks on or off.

Figure 7.

Regulatory Feature ‘Feature context view’. This view displays the general context 25 kb upstream and downstream of a feature, with genes and neighbouring elements. As in the summary view, for each cell type inactive features are greyed out, with sparse coloured lines indicating their underlying function. At the bottom, FANTOM5 elements and TarBase target regions are indicated.

Figure 8.

Constructing a BioMart query. This figure exemplifies the construction of a BioMart query to obtain all regulatory features for K562, within the region 1:1000 000–10 000 000 and display a varied number of properties for those regulatory regions, including their stable ids.

Figure 9.

VEP output using motif feature information. Subsection of the VEP report on SNP rs694061. The VEP reports whether a SNP affects the binding affinity of a motif feature (i.e. whether position of the SNP contains at least 1.5 bits of information on the PWM).