Description
GeneHancer is a database of human regulatory elements (enhancers and promoters)
and their inferred target genes, which is embedded
in GeneCards, a human gene
compendium.
The GeneHancer database was created by integrating >1 million regulatory elements
from multiple genome-wide databases.
Associations between the regulatory elements and target genes
were based on multiple sources of linking molecular data, along with distance,
as described in Methods below.
The GeneHancer track set contains tracks representing:
- Regulatory elements (GeneHancers)
- Gene transcription start sites
- Interactions (associations) between regulatory elements and genes
- Clustered interactions, by gene target or GeneHancer
The full set of elements and interactions is included, along with a highly filtered
"double elite" subset.
Display Conventions
Each GeneHancer regulatory element is identified by a GeneHancer id.
For example: GH0XJ101383 is located on chromosome X, with starting position of 101,383 kb
(GRCh38/hg38 reference).
Based on the id, one can obtain full GeneHancer information, as displayed in the Genomics
section within the gene-centric web pages of GeneCards. Links to the GeneCards information pages
are provided on the track details pages.
For the interaction tracks (Clusters and Interactions) a slight offset can be noticed between
the line endpoints. This helps to identify the start and end of the feature. In this case,
the higher point is the source (enhancers) and the lower point is the target.
Regulatory elements
Colors are used to distinguish promoters and enhancers and to indicate the GeneHancer element confidence score:
Promoters:
High
Medium
Low
Enhancers:
High
Medium
Low
Gene TSS
Colors are used to improve gene and interactions visibility.
Successive genes are colored in different colors, and interactions of a gene have the same color.
Interactions
The Interactions view in Full mode shows GeneHancers and target genes connected by curves or
half-rectangles (when one of the connected regions is off-screen).
Configuration options are available to change the drawing style, and to limit the view to
interactions with one or both connected items in the region.
Interactions are identified on mouseover or clicked on for details at the end regions, or at
the curve peak, which is marked with a gray ring shape. Interactions in the reverse direction
(Gene TSS precedes GeneHancer on the genome) are drawn with a dashed line.
Clusters
The Clusters view groups interactions by target gene; the target gene and all GeneHancers
associated with it are displayed in a single browser item. The gene TSS and associated GeneHancers
are shown as blocks linked together, with the TSS drawn as a "tall" item, and the
GeneHancers drawn "short".
A user configuration option is provided to change the view to group by GeneHancer
(with tall GeneHancer and short TSS's).
Clusters composed of interactions with a single gene are colored to correspond to the gene,
and those composed of interactions with multiple genes are colored dark gray.
Methods
GeneHancer identifications were created from >1 million regulatory elements
obtained from seven genome-wide databases:
- ENCODE project
Z-Lab Enhancer-like regions (version v3)
- Ensembl regulatory build (version 92)
- FANTOM5 atlas of active enhancers
- VISTA Enhancer Browser
- dbSUPER super-enhancers
- EPDnew promoters
- UCNEbase ultra-conserved noncoding elements
Employing an integration algorithm that removes redundancy, the GeneHancer pipeline
identified ˜250k integrated candidate regulatory elements (GeneHancers).
Each GeneHancer is assigned an annotation-derived confidence score.
The GeneHancers that are derived from more than one information source are defined
as "elite" GeneHancers.
Gene-GeneHancer associations, and their likelihood-based scores, were generated
using information that helps link regulatory elements to genes:
- eQTLs (expression quantitative trait loci) from GTEx (version v6p)
- Capture Hi-C promoter-enhancer long range interactions
- FANTOM5 eRNA-gene expression correlations
- Cross-tissue expression correlations between a transcription factor interacting
with a GeneHancer and a candidate target gene
- Distance-based associations, including several approaches:
- Nearest neighbors, where each GeneHancer is associated with its two proximal genes
- Overlaps with the gene territory (intragenic)
- Proximity to the gene TSS (<2kb)
Associations that are derived from more than one information source are defined
as "elite" associations, which leads to the definition of the "double elite"
dataset - elite gene associations of elite GeneHancers.
More details are provided at the GeneCards
information page.
For a full description of the methods used, refer to the GeneHancer manuscript1.
Source data for the GeneHancer version 4.8 was downloaded during May 2018.
Data Access
Due to our agreement with the Weizmann Institute, we cannot allow full genome
queries from the Table Browser or share download files. You can still access
data for individual chromosomes or positional data from the
Table Browser.
GeneHancer is the property of the Weizmann Institute of Science and
is not available for download or mirroring by any third party
without permission. Please contact the Weizmann Institute directly for
data inquiries.
Credits
Thanks to Simon Fishilevich, Marilyn Safran, Naomi Rosen, and Tsippi Iny Stein of the GeneCards
group and Shifra Ben-Dor of the Bioinformatics Core group at the Weizmann Institute,
for providing this data and documentation, creating track hub versions of these tracks
as prototypes, and overall responsiveness during development of these tracks.
Contact:
simon.
fishilevich@weizmann.
ac.
il
Supported in part by a grant from LifeMap Sciences Inc.
References
Fishilevich S., Nudel R., Rappaport N., Hadar R., Plaschkes I., Iny Stein T., Rosen N., Kohn A., Twik M., Safran M., Lancet D. and Cohen D. GeneHancer: genome-wide integration of enhancers and target genes in GeneCards, Database (Oxford) (2017), doi:10.1093/database/bax028. [PDF] PMID 28605766
Stelzer G, Rosen R, Plaschkes I, Zimmerman S, Twik M, Fishilevich S, Iny Stein T, Nudel R, Lieder I, Mazor Y, Kaplan S, Dahary, D, Warshawsky D, Guan- Golan Y, Kohn A, Rappaport N, Safran M, and Lancet D. The GeneCards Suite: From Gene Data Mining to Disease Genome Sequence Analysis, Current Protocols in Bioinformatics (2016), 54:1.30.1-1.30.33. doi: 10.1002/cpbi.5. PMID 27322403
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