Tool for regulatory motif detection in signaling network
RMOD?
RMOD is a computational tool for identifying regulatory motifs and their regulatory properties in signaling network. Utilizing network compression and graph pattern matching based on regulatory motif information, this tool enables users to detect minimal regulatory motifs either within the whole network or along a user-defined path. The minimal regulatory motifs are expanded by recovering original paths from compressed edge and then, individual regulatory motifs are identified. Thus, RMOD provides an integrated view of the regulatory motifs and the mechanism underlying their regulatory activities within the network. Furthermore, the graphical user interface of RMOD facilitates the designing and visualizing of novel regulatory motifs and networks.
Notice
2012/09/01 RMOD is released.

Workspace
Network ID
View
Remove
Download
Analysis
Upload network file
Current network
Nodes
Node ID
Label
Update
Remove
Edges
Edge ID
Source
Target
Effect
Update
Remove
Analysis Options
Input network
Query motifs
Analysis scope
to
Result Summary
Motif Name
Count
Motif Structure
Motif Members
Num
Size
Effect
Length
Path
Known Regulatory Motifs
Name
Structure
View
New Regulatory Motifs
Regulatory motif name
Current regulatory motif
Saved Regulatory Motifs
Number
Name
View
Remove
Query motifs
Content


 1. What is RMOD?
Regulatory motifs are patterns of activation and inhibition that appears repeatedly in various signaling networks with specific regulatory properties (Wolf D.M. et al., 2003). RMOD is a computational tool for identifying regulatory motifs and their regulatory properties in signaling network. Utilizing network compression and graph pattern matching based on regulatory motif information, this tool enables users to detect minimal regulatory motifs either within the whole network or along a user-defined path. The minimal regulatory motifs are expanded by recovering original paths from compressed edge and then, individual regulatory motifs are identified. Thus, RMOD provides an integrated view of the regulatory motifs and the mechanism underlying their regulatory activities within the network. Furthermore, the graphical user interface of RMOD facilitates the designing and visualizing of novel regulatory motifs and networks.

 2. Network data format
For loading network data from a file, RMOD supports a simple text file format (each line contains regulator, relation, and target). Hence, a line in the input file looks like this: [ID-regulator-vertex] [+,-] [ID-target-vertex]. The sample input file is illustrated in following figure.
							L	+	mPer
							mPer	+	Per
							Per	+	PC
							mCry	+	Cry
							Cry	+	PC
							mBmal1	+	Bmal1
							Bmal1	+	CB
							mRv	+	Rv
							Rv	-	mBmal1
							mRora	+	Rora
							Rora	+	mBmal1
							PC	-	CB
							CB	+	mRv
							CB	+	mRora
							CB	+	mCry
							CB	+	mPer
							CB	-	mBmal1
					
 3. Managing networks
RMOD provides network management functionality via network editor interface.
3.1. Workspace
RMOD offers workspace for managing several networks. For each of network, user can view, delete, download network or transfer network into motif analysis tool

3.2. Creating network
RMOD offers network editor functionality for network manipulation and network creation from scratch, such as adding and moving vertices and edges. After selecting view button of uploaded network in workspace, user can edit selected network by inserting, deleting and updating node and edge in network viewer and data table.

 4. Designing query regulatory motifs
In order to detect regulatory motifs in network, it is necessary to prepare query regulatory motifs in advance and tranfer query regulatory motifs to motif explorer interface. In motif design interface, user can make query minimal regulatory motifs, save them and transfer regulatory motifs to motif explorer interface.
4.1. Selecting known regulatory motifs
RMOD offers three representative classes of regulatory motifs such as bistabe-switch [1], oscillation [2] and adaptation [3] motif. These are two and three node enzyme network topologies which are parametrically robust in exhibiting dynamic behaviors. These known regulatory motifs are shown in known regulatory motif table. Clicking "select all known regulatory motif" button temporarily saves them as query regulatory motifs.


[1] Shah N.A. et al. (2011) Robust network topologies for generating switch-like cellular responses. PLoS Comput Biol. 7, e100208
[2] Novak B. et al. (2008) Design principles of biochemical oscillators. Nat Rev Mol Cell Biol. 9, 981-991
[3] Ma W. et al. (2009) Defining network topologies that can achieve biochemical adaptation. Cell, 138, 760-773
4.2. Making novel regulatory motifs
Since there still remains novel regulatory motifs to discover, RMOD provides regulatory motif design functionality for creating novel regulatory motif queries. Simply, user can make novel query motifs by drawing signed directed graphs

4.3. Transfering query regulatory motifs
For saved regulatory motifs, user can transfer regulatory motifs into motif explorer interface by clicking transfer button. In addtion, user can manage current saved regulatory motifs by clicking view and remove button.

 5. Search for regulatory motifs
If network data is uploaded and regulatory motifs are selected, user can detect regulatory motifs in network by clicking find button after designating search scope.
5.1. Search option
RMOD allows regulatory motif search in network or along the path. Especially, RMOD provides a mechanism to query a network by allowing the user to select a source node and a target node and then finding the shortest paths that connect these two elements in a network. Along the pathway, RMOD detects all the regulatory motifs including nodes of the pathway. The path is marked as green edge

5.2. Search results
RMOD displays the result of regulatory motif search in Result Summary table.

Clicking each regulatory motif in Result Summary table shows regulatory motif structure in motif structure viewer and members in Motif Member table.

Motif Member table show size of regulatory motif, sign and length of path composing regulatory motif. Clicking each member in Motif Member table highlights the regulatory motif in network viewer.

 6. Viewing network
6.1. Network layout
RMOD provides four different layout algorithms: force-directed, circle, radial, and tree layout. These layout algorithms are based on functionalities in cytoscape web. Basically, all network viewers initially exhibit loaded network based on force-directed layout algorithm. User can apply one of these layout algorithms to loaded network by clicking mouse right button and selecting one of them.

6.2. Network color
RMOD represents edge colors based on the effect of edge.
 if the effect of edge is activation, then the color of edge is blue.
 if the effect of edge is inhibition, then the color of edge is red.

RMOD represents node colors based on the number of indegree and outdegree of the node.
 if the indegree of the node is zero, then the color of the node is pink.
 if the outdegree of the node is zero, then the color of the node is gray.
 if both indegree and outdegree are nonzero, then the color of the node is blue.

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