Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Mar 24;16(1):56.
doi: 10.1186/s13059-015-0621-5.

The ensembl regulatory build

Daniel R Zerbino  1 , Steven P Wilder  2 , Nathan Johnson  3 , Thomas Juettemann  4 , Paul R Flicek  5
Affiliations

The ensembl regulatory build

Daniel R Zerbino et al. Genome Biol. .

Abstract

Most genomic variants associated with phenotypic traits or disease do not fall within gene coding regions, but in regulatory regions, rendering their interpretation difficult. We collected public data on epigenetic marks and transcription factor binding in human cell types and used it to construct an intuitive summary of regulatory regions in the human genome. We verified it against independent assays for sensitivity. The Ensembl Regulatory Build will be progressively enriched when more data is made available. It is freely available on the Ensembl browser, from the Ensembl Regulation MySQL database server and in a dedicated track hub.

PubMed Disclaimer

Figures

Figure 1
Figure 1
The Regulatory Build process. In a first step we run segmentation software across multiple cell types. For each cell type and at each base pair, the genome is assigned a state, identified by an arbitrary number assigned by the segmentation software. We assign to each state a non-unique functional label, represented by its color on the browser, as shown at the top. For each state at each base pair, we compute the number of cell types sharing that state at that position, as shown in the center of the figure. Having selected relevant states and set some thresholds, we define regions of interest, which are the foundation of the regulatory build. These regions are then complemented with unannotated ChIP-Seq transcription factor binding site peaks and unannotated DNase1 hypersensitivity sites.
Figure 2
Figure 2
Experimental marks associated with different labels. This heatmap represents the experimental marks and the label associated with each state. The states were defined by Segway, and the labels assigned by the Ensembl Regulatory Build a posteriori. Although the label assignment relies mainly on overlaps with known features, the states with the same labels co-cluster based on their experimental marks. The main exception are the promoter flanking states, which cluster either with promoters or with distal cis-regulatory elements. In effect, these states tend to represent a mixture of the other two.
Figure 3
Figure 3
Decision tree assigning labels to unsupervised segmentation states.
See this image and copyright information in PMC

References

    1. Freedman ML, Monteiro AN, Gayther SA, Coetzee GA, Risch A, Plass C, et al. Principles for the post-GWAS functional characterization of cancer risk loci. Nat Genet. 2011;43:513–8. doi: 10.1038/ng.840. - DOI - PMC - PubMed
    1. McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, et al. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature. 2011;471:216–9. doi: 10.1038/nature09774. - DOI - PMC - PubMed
    1. Levine M, Tjian R. Transcription regulation and animal diversity. Nature. 2003;424:147–51. doi: 10.1038/nature01763. - DOI - PubMed
    1. Jaenisch R, Bird A. Epigenetic regulation and gene expression: how the genome integrates integrates intrinsic and environmental signals. Nat Genet. 2003;33:245–54. doi: 10.1038/ng1089. - DOI - PubMed
    1. Maston GA, Evans SK, Green MR. Transcriptional regulatory elements in the human genome. Annu Rev Genom Human Genet. 2006;7:29–59. doi: 10.1146/annurev.genom.7.080505.115623. - DOI - PubMed

Publication types

Substances