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BEReX v.1.0
Biomedical Entity-Relationship eXplorer
User Guide
Minji Jeon1, Sunwon Lee2, Kyubum Lee2, Aik-Choon Tan3 and Jaewoo Kang1;2
1Interdisciplinary Graduate Program in Bioinformatics, Korea University, Seoul, Korea 2Department of Computer Science and Engineering, Korea University, Seoul, Korea
3Department of Medicine/Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
*The T-rex figure is adapted from the animated movie “Meet the Robinsons” (2007).
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* For bugs and inquiries, please contact:
Minji Jeon ([email protected]) Jaewoo Kang ([email protected])
* Project website: http://infos.korea.ac.kr/berex
* BEReX is licensed under the GNU General Public License and is 100% freely available to both commercial
and academic users. See the file LICENSE.txt in the BEReX distribution package or this URL for the full text
of the license: http://www.gnu.org/licenses/gpl.html
* BEReX is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied
warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public
License for more details.
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1. System Requirements
1) OS: Windows, Mac OS X, or Linux
2) Java Runtime: JRE6 or later, or JDK1.6 or a later version is needed to run the application
3) CPU: A reasonably fast CPU will work such as Intel Core-i3 or better
4) Memory: 4GB or more is recommended
5) Storage Space: 3.12GB of extra space is required
2. Installation Guide
1) Install JRE from http://www.oracle.com/technetwork/java/javase/downloads/index.html (skip this step if you have JRE6 or later, or JDK1.6 or later)
2) Download BEReX (v.1.0) and unzip the package file:
Windows : berex-v1-windows.zip (184MB) (http://infos.korea.ac.kr/berex/Windows/berex-v1-
windows.zip)
Mac : berex-v1-mac.zip (184MB) (http://infos.korea.ac.kr/berex/Mac/berex-v1-mac.zip) Linux : berex-v1-linux.zip (184MB) (http://infos.korea.ac.kr/berex/Linux/berex-v1-linux.zip)
3) Run BEReX.bat (for Windows) / BEReX.sh.command (for Mac) / BEReX.sh (for Linux)
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3. User Interface Overview
Users can query BEReX for any combination of genes, drugs, diseases, pathways, miRNAs, transcription
factors, and gene ontology terms by using keywords. The query box and search button are located at the top
of the application window. The BEReX exploration window at the center shows the query results in a graph.
Users can interactively expand/modify the graph to construct custom pathway networks of their interest. The
tree view window at the top right shows the entity-relation information of a selected node. The window below
that shows the details of a selected node or edge and provides links to external sources such as PubMed
articles that support the relation. The window at the bottom left allows users to filter information by particular
entity types, relation types, and data sources. Finally, users can save the current graph as a file for later use
or export the graph as an image through the file menu at the top.
4. Tutorial: BCR-ABL1 Use Case
Here, we show how we generate the BCR-ABL1 network in Figure 1 (main paper). Please follow the next
steps:
1) Enter “BCR ABL1” in the query box and click on the ‘Search’ button.
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2) A sub-network that matches
the query appears in the
exploration window as shown
below. In addition to the query
nodes (BCR and ABL1),
BEReX automatically selects
a small number of additional
entities that are highly related
to the query nodes, and adds
them to the network (TP53,
SRC, UBC, and HSP90AA1).
We use a PageRank-based
scoring algorithm for
determining the relevancy.
Please note that BEReX’s
response time may be slow in
the beginning due to the time
required for the system
memory cache to warm up
(i.e., a good portion of the
working database is loaded
into the memory).
3) The tree view window at the top-right
shows the full interaction information for
the two query nodes as shown below.
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4) The information window right
below the tree view window
shows the detailed information
about a selected node or edge.
The figure below shows the
information about ABL1.
5) The window at the bottom-right shows the
shortest paths between nodes selected by a user.
The figure below shows the result after the user
selected TP53 and SRC. The shortest paths are
shown in the order of their significance determined
by our scoring algorithm. Users can add one of the
shortest paths to the current graph by double-clicking
one from the list.
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6) Now, select both BCR and ABL1 by holding down the ‘SHIFT’ key and then clicking on each node. The
gene names on the two nodes will become highlighted in blue. Then, right-click on either of the two
selected nodes, which will bring up a context-menu as shown below.
7) Choose “Expand selected entity type” -> “Drug.” As a result, “imatinib” is added as below.
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8) Add two more drugs by repeating this process. If you want to add more than one entity at a time, go to
“Option” -> “Expand by” on the menu bar at the top and choose the number of entities you want added
each time. The default value is one. The resulting network is shown below. Please note that the nodes
are rearranged to improve readability.
9) Users can obtain supporting information for any relation in the current graph by clicking on an edge. For
example, the figure below shows the information window after a user clicks on the link between fasudil
and ABL1. It shows the link to the PubMed article that reports the relationship between fasudil and ABL1,
and that the source of the information is the PhamGKB database. Clicking on the PubMed link will show
the supporting article in the user’s main web browser.
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10) Now, let us add five disease/symptom nodes by following the process explained above.
11) We want to add miRNAs that interact with ABL1. This time, select only ABL1 and execute “Expand by
selected entity type” -> “miRNA” until five miRNAs are added.
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12) Add five pathways that are related to both ABL1 and BCR. Highlight both ABL1 and BCR by using ‘SHIFT
+ Click.’ Then, right-click on either ABL1 or BCR to select “Expand by selected entity type” -> “Pathway.”
Notice that RAC1 and CDC42 have been added as a result of this step. When an entity is expanded from
a set consisting of more than one node, BEReX adds a shortest path from the expanded (target) node to
each of the source nodes in the original set. For example, “Viral myocarditis pathway” has a direct link to
ABL1 (i.e., a shortest path) but has no connection to BCR. BEReX adds the highest-ranked shortest path
between them, which is in this case, “Viral myocarditis pathway” – RAC1 – BCR, among potentially many
candidate shortest paths. The relevance is determined by the PageRank-based scoring algorithm
explained in the main paper and the supplementary methods.
13) We now expand the graph for Gene Ontology terms. Select both ABL1 and BCR, and execute “Expand
by selected entity type” -> “Gene Ontology (Molecular Function).”
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14) Choose “Option” -> “Expand by” -> 5. Highlight ABL1 by clicking on it. Right-click on ABL1 and execute
“Expand by selected entity type” -> “Transcription Factor.” This will add five transcription factors as shown
below.
15) We delete RAC1, CDC42, SOS1, and MAPK14 to obtain the same network as in Figure 1. Node deletion
is done by right-clicking on the node to be deleted and clicking on “Delete this node.”
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16) Now, we want to store the current network for later use. Go to “File” -> “Save”; enter the file name for
your graph; and then click on the save button. The saved network can be loaded later through the “File”
-> “Open” menu. Note that the current version is capable of storing only the topology, not the layout, of
the graph. We will address this issue in the next version.
17) BEReX also allows graphs to be imported from and exported to a popular standard format such as PSI-
MI(Proteomics Standards Initiative-Molecular Interaction) version 2.5, SIF(Simple Interaction Format),
and GML(Graph Modeling Language). Go to “File” -> “Import/Export” to import or export a graph.
18) Users can export the current network as an image, either in EPS or JPG format. Go to “File” -> “Save as
Image”; enter the name for your image file; and then click on the save button.
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19) Users can change the graph layout through the “Option” -
> “Graph Layout” menu. Currently, BEReX supports two layouts
including the FR layout (Fruchterman-Rheingold algorithm) and the
KK layout (Kamada-Kawai algorithm).
20) Query Suggestions: BEReX provides a flexible query interface. Users can search for an entity even
when they do not know the exact names of the entities, by using wildcards such as “*” or “?”. The figure
below shows the pop-up dialog box generated by BEReX for a user query “parkin*.” From the
suggestion list, users can select the one that matches their search.
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21) Database Updates: BEReX allows users to conveniently update their databases through the “Help” ->
“Check for Updates” menu. BEReX compares the versions of the users’ databases with the version of
the database in the server. If there is an updated database available, users are allowed to update their
databases by clicking on the “Start” button in the update dialog box shown in the figure below.