The BioMart interface to the eMouseAtlas gene expression database EMAGE.

Abstract

Here, we describe the BioMart interface to the eMouseAtlas gene expression database EMAGE. EMAGE is a spatiotemporal database of in situ gene expression patterns in the developing mouse embryo. BioMart provides a generic web query interface and programmable access using web services. The BioMart interface extends access to EMAGE via a powerful method of structuring complex queries and one with which users may already be familiar with from other BioMart implementations. The interface is structured into several data sets providing the user with comprehensive query access to the EMAGE data. The federated nature of BioMart allows scope for integration and cross querying of EMAGE with other similar BioMarts.

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Original Article
The BioMart interface to the eMouseAtlas
gene expression database EMAGE
Peter Stevenson*, Lorna Richardson, Shanmugasundaram Venkataraman, Yiya Yang and
Richard Baldock
The Institute of Genetics and Molecular Medicine, MRC Human Genetics Unit, Western General Hospital, Edinburgh EH4 2XU, UK
*Corresponding author: Tel: +44 (0)131 332 2471; Fax: +44 (0)131 467 8456; Email: peter.stevenson@hgu.mrc.ac.uk
Submitted 1 April 2011; Revised 2 June 2011; Accepted 13 June 2011
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Here, we describe the BioMart interface to the eMouseAtlas gene expression database EMAGE. EMAGE is a spatiotemporal
database of in situ gene expression patterns in the developing mouse embryo. BioMart provides a generic web query
interface and programmable access using web services. The BioMart interface extends access to EMAGE via a powerful
method of structuring complex queries and one with which users may already be familiar with from other BioMart imple-
mentations. The interface is structured into several data sets providing the user with comprehensive query access to
the EMAGE data. The federated nature of BioMart allows scope for integration and cross querying of EMAGE with
other similar BioMarts.
Database URL: http://biomart.emouseatlas.org
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Project description
EMAGE (http://www.emouseatlas.org/emage) is a freely
available, curated, online database of in situ gene expres-
sion patterns in the developing mouse embryo (1–3). Gene
expression domains extracted from raw images are inte-
grated spatially into a set of standard 3D virtual mouse
embryo models at different stages of development. In add-
ition, an anatomy ontology (4) is used to describe sites of
expression using text annotations. The EMAGE web site
provides specialized interfaces that allow users to search
for gene expression patterns. Uniquely, EMAGE searches
can be made using spatially defined regions, as well as
standard text based querying. Search results concentrate
on providing access to images of original experiments and
mapped expression patterns. However, the database also
contains a considerable amount of information describing
the experiments that were carried out to produce the gene
expression patterns, as well as the data provenance. Much
of this ancillary data, although visible on the detailed sub-
mission pages, was not directly searchable in the EMAGE
web site before the implementation of the BioMart (5)
interface (http://biomart.emouseatlas.org). BioMart allows
a greater range of possible queries that can include experi-
ment details and other ancillary data. It also allows the
possibility of integration with other BioMarts. However,
BioMart cannot currently provide spatial searches or
ready access to image data. The EMAGE web site and the
BioMart interface therefore should be seen as complemen-
tary methods of querying EMAGE data content.
Data content
The EMAGE data is divided into three BioMart databases.
EMAGE browse repository BioMart database
This database provides a summary view of the curated
EMAGE submissions as well as additional assays that are
not suitable for spatial mapping and have therefore
not been included as full EMAGE submissions. It has a
single data set. The Repository Browse data set has a
limited number of filters and attributes providing an
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overview of the EMAGE data. It is the equivalent of the
‘browse’ and ‘quick search’ options on the EMAGE
web site.
EMAP anatomy ontology BioMart database
This database provides a view of the standard anatomy
ontology of mouse development (EMAP) as used in the
EMAGE database. The anatomy ontology is constructed as
a directed acyclic graph (DAG), with a parent and child re-
lationship, the relationship being ‘part-of’, for example
‘elbow’ is part-of ‘arm’. The ontology is defined for each
Theiler Stage (6) of development and for all stages com-
bined (the abstract ontology). In the BioMart interface
these aredifferentiated by
stages’ and ‘abstract’. Each node in the DAG is given a com-
ponent name and a unique ID. The database contains
two data sets.
the descriptions‘timed
Anatomy components (component details) data
set. This data set provides details of the components of
the ontology. The component name, stage and ID form
the BioMart filters for this data set as well as being default
attributes. Further attributes include the DAG relationship
information plus additional ontological data.
This data set can be linked in a query to the EMAGE
submission data set and to the EMAGE text expression
data set. However, a query for gene expression using
this data set will find results only for that single anat-
omy component of the ontology. To search for expres-
sion in a component and its children, the Anatomy
Components (including subcomponents) data set should
be used.
Anatomy components (including subcomponents).
This data set consists of the anatomy ontology components
at each timed stage along with each of the child sub-
components that are ‘part-of’ that particular component.
The filters for this data set are the component name, ID
and Theiler stage. The attributes available are name, ID
and component path of the parent and child term, plus
Theiler stage. The ‘component path’ is the series of compo-
nent names from the highest level parent through its des-
cendants to the component term.
This data set can be linked in a query to the EMAGE
submission data set and to the EMAGE text expression
data set.
EMAGE gene expression BioMart database
This database comprises the main source of EMAGE gene
expression and ancillary data. The database contains
four data sets. Of these, the primary data set is the
EMAGE submission data set. The other three data sets, as
well as the anatomy ontology data set, can be linked in a
query to allow comprehensive search capabilities where
this is required. Limitations in the translation of the data-
base schema from native EMAGE to BioMart have resulted
in this somewhat fragmented data model. Nonetheless,
access to all the EMAGE data can be achieved either in a
single or linked BioMart query.
EMAGE submission data set. This data set comprises
the bulk of data in EMAGE. An EMAGE submission gener-
ally will be one specimen stained for the expression of one
gene or protein at one point in embryonic development.
Associated with each submission there may be details of
the experiment, annotated sites of expression, the names
and details of the data submitter or source, relevant links to
other data, acknowledgements to data providers and/or
references, details of the images, associated gene synonyms
and GO terms. Many search attributes are available and
have been grouped broadly in the categories just described.
The filters for this data set are grouped by gene, submis-
sion, experiment, and links. The EMAGE submission data set
can be linked in a single query with the EMAGE experiment
data set or the EMAGE spatial expression annotation data
set if required.
EMAGE experiment data set. This data set consists of
data pertinent to the in situ experiment that produced the
gene expression image used in a particular EMAGE submis-
sion. This covers preparation and description of the speci-
men used the targeted gene, detection reagent type, probe
sequences and cell line data. Common filters and attributes
are grouped together for convenience and certain attri-
butes are set as default for results. The EMAGE experiment
data set can be linked in a single query with the EMAGE
submission data set and the EMAGE text expression anno-
tation data set if required.
EMAGE spatial expression data set. This data set
consists of data pertinent to spatial gene expression data
recorded in EMAGE. A relatively limited set of filters are
available for this data set and the attributes grouped as
‘Mapped position attributes’ are probably only useful in
the context of the full EMAGE database where the spatial
information can be used for querying and visualization.
Nonetheless, an indication of spatial gene expression can
be found using the filters provided. The most useful of the
expression filters is probably ‘strength’. EMAGE gene ex-
pression strength is indicated with values of strong, mod-
erate, weak, possible or not detected. The default attribute
‘EMAGE ID’ is returned in the results table as a URL link
to the submission page where full details and visualiza-
tions of the mapped expression patterns can be seen.
The EMAGE spatial expression data set can be linked in a
single query with the EMAGE submission data set if
required.
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EMAGE text expression annotation data set. This
data set comprises the EMAGE gene expression data that
has been annotated using text descriptions from the anat-
omy ontology. The filters for this data set, which are
grouped as expression text annotation filters, include
ontology ID along with expression strength and pattern.
Additional filters are also available, under the group head-
ings of gene, submission and experiment filters. Attributes
are grouped in the same way as the filters. This data set can
be linked in a single query with the EMAGE experiment
data set if required. This allows additional experiment at-
tributes to be found that are not available from the text
expression data set. This data set can also be linked in a
query with the anatomy ontology data set in order to
obtain more information about an ontology term such as
its name, path and stage range.
Query examples
A number of example queries are given in this section.
These examples demonstrate the use of the different
data sets described earlier, and show how these can be
used to provide powerful and flexible searches of the
EMAGE data. Screenshots of each query are available as
online Supplementary Data.
(1) EMAGE browse repository database.
Query #1. ‘Find a summary of gene expression for Fgf
family genes at Theiler Stage 18’
Data setFilters Attributes
Repository BrowseGene/Protein: fgf%
Theiler Stage: 18
Resource
ID
Gene/Protein
Detection Reagent
Theiler Stage
Stage Given
Assay
Specimen Type
Mutant Allele
URL
Querying the Repository Browse data set provides an
overview of gene expression data available in the EMAGE
repository as illustrated by Query 1. The query has incorpo-
rated the wild-card symbol (%) in order to find all gene
symbols starting with ‘fgf’. The attribute ‘URL’ provides
a link to either the full submission description in EMAGE
for fully curated data, or to the original image source in an
external resource if the submission is not fully curated in
EMAGE.
(2) EMAP anatomy ontology database.
Query #2. ‘Find text annotated gene expression in the limb
for the Wnt and Hox gene families’.
Data set Filters Attributes
Anatomy
Components
(including
subcomponents)
EMAGE text
expression
annotation
data set
Anatomy
component
name: limb
Parent component name
Parent component path
Child component name
Child component path
Strength (text annotation)
Pattern (text annotation)
MGI gene symbol
Emage ID
Theiler stage
MGI gene
symbol:
Wnt%, Hox%
The Anatomy Components (including subcomponents)
can be used to find gene expression annotation in
EMAGE when used as a linked database query as illustrated
by Query 2. The query will return results for the component
chosen as a filter and all of its subcomponents. Here, the
query term ‘limb’ also retrieves expression in, for example,
‘forelimb bud’. The ‘Emage ID’ attribute appears in the
results as a link to the full submission description in
EMAGE (as it does in all cases where the EMAGE ID is
chosen as an attribute).
(3) EMAGE gene expression database.
Query #3. ‘Find the EMAGE submissions and details of
probes used to detect the Fgf gene family at Theiler
stages 16–20 where the specimen type is section data
(or unknown) and the assay quality is the highest value’.
Data set Filters Attributes
EMAGE
submission
data set
MGI gene
symbol: fgf%
Theiler stage: 16–20
Assay quality: 3
Specimen type:
section, unknown
MGI gene symbol
Emage ID
Theiler stage
Staining procedure
Embedding reagent
Clearing method
Fixation
Specimen type
Assay quality
Detection reagent identifier
Detection reagent
sequence type
Detection reagent notes
ISH probe generated from
ISH probe chemistry
ISH probe strand
ISH probe label
EMAGE
experiment
data set
Querying the EMAGE gene expression BioMart database
allows potentially complex sets of query conditions and
output parameters to be defined. This provides a powerful
tool to filter views of the gene expression data, its experi-
mental details, and other associated data as illustrated
by Query 3. The query is constructed to filter the EMAGE
submission data set for gene, stage, assay quality and
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specimen type. The query requires to be linked with the
EMAGE experiment data set in order to show attributes
of the experiment and detection reagents.
Query #4. ‘For the detection reagent with the identifier
MGI:1334951 (a specific Fgf8 riboprobe) find the EMAGE
submissions and the publication details of the experiment
along with any further published references to this
experiment’.
Data setFilters Attributes
EMAGE
experiment
data set
Detection reagent
identifier:
MGI:1334951
MGI gene symbol
Emage ID
Theiler stage
Detection reagent identifier
Authors
Accession (reference)
Authors
Publication year
Title
Publication name
Publication issue
Publication volume
Pages
EMAGE
submission
data set
For a particular in situ hybridization probe of interest a
user can find all of the instances of gene expression re-
corded in EMAGE for that probe, along with references
to the experiment in the published literature as illustrated
by Query 4. The query is filtered in the EMAGE experiment
data set using the detection reagent identifier. The query is
linked with the EMAGE submission data set in order to
show the various attributes of the publication details.
Discussion and future direction
The EMAGE database was conceived primarily to provide
a unique method of collating, curating, querying and ana-
lysing spatiotemporal patterns in the mouse embryo includ-
ing gene expression. In order for the gene expression data
to be provided in context, additional metadata pertaining
to the in situ experiments is also included in the database.
This data is curated rigorously by EMAGE editorial staff to
provide a high quality data set. The primary focus of the
EMAGE website is to provide tools to search for gene ex-
pression, to display this data to users in a visual form as far
as possible, and to enable spatial query and analysis. The
implementation of BioMart in EMAGE now allows an add-
itional text based interface that addresses a need for
focussed searches across all of the text based information
held in EMAGE.
The data mining aspect of BioMart is an important factor
in providing additional search functionality to EMAGE.
However, BioMart also provides a standardized web inter-
face, an application programming interface (API) and a
RESTful web service. These interfaces are being increasingly
adopted by a variety of well known biological databases
and are described further by Haider et al. (7). This means
that biological researchers and programmers may already
be familiar with the BioMart interface and may prefer to
access a database such as EMAGE using tools and tech-
niques that they have already used with other BioMart
implementations.
Another important aspect of BioMart is that it allows
federated queries between databases (5). The ability to in-
tegrate data in this way will be the focus of future devel-
opment of the EMAGE BioMart. A number of existing and
proposed gene expression databases share a high degree of
commonality with the EMAGE database. These include
Eurexpress (8) a transcriptome-wide mouse gene expression
study that shares the same anatomy ontology. Eurexpress
currently has its own BioMart implementation but it is
planned to absorb this data into EMAGE, in which case a
unified Biomart will be provided. GUDMAP (9), a genito–
urinary molecular anatomy project also has a common
anatomy ontology and shares database administration
and development with EMAGE. It is planned to provide a
BioMart implementation for GUDMAP in the future. It may
be possible to integrate this data into a single BioMart in-
stance with EMAGE but more likely would be to link these
in a federated manner. The eChickAtlas project (http://
www.echickatlas.org/) is a chicken embryo gene expression
database that is currently under development. This data-
base will use an ontology derived from, and mapped to,
the same source as the EMAP mouse ontology. This pro-
vides scope for interesting cross species queries to be car-
ried out and could be implemented using the federated
nature of BioMart.
Integration of databases in this way should provide re-
searchers concerned with gene expression data access to a
large volume of information in an easily accessible and uni-
fied manner.
Finally, extending BioMart to spatially mapped data
opens up the possibility of specifically spatial queries and
filters. These could be implemented via simple ‘punch-out’
type capabilities to the EMAGE graphical interfaces or via
stored queries held in the database but will require exten-
sion of the underlying BioMart model. If this were possible
then it would provide a more significant level of integra-
tion through to spatially organized data.
Supplementary Data
Supplementary data are available at Database Online.
Acknowledgements
The authors thank Damian Smedley at the EBI and Bernard
Haggertyherein theMRC HGUfor helping the
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development of the EMAGE BioMart and both the OICR
and EBI for linking EMAGE on their portal.
Funding
UK Medical Research Council (MRC; as part of the
MouseAtlas project at the MRC Human Genetics Unit).
Funding for open access charge: Medical Research Council.
Conflict of interest. None declared.
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