Manual (beta version)
In-silico Cancer Network
(Cancer Network System)
Prof. Kwang-Hyun Cho’s Laboratory for
Systems Biology and Bio-Inspired
Engineering, KAIST
Copyright© Prof. Kwang-Hyun Cho’s SBIE, KAIST
Kim, Ger-Yong
Research Period: 2007.07.01~2009.10.01
- Contents 1. IsCN Program Description
2. Starting IsCN
3. How to use
3.1. Data Searching
3.2. Network Visualization
3.3. Boolean Simulation
Appendix A. Network Viewer _ Initial Visualization
Appendix B. Network Viewer _ Network Editing
Appendix C. Boolean Simulation _ Simulation Information Setting
Appendix D. Boolean Simulation _ Simulation Results Updating
3. How to use
IsCN is able to draw pathways on a computer screen by searching proteins and is able
to simulate them. It can be divided into 3 modules(Data searching, Visualization,
Simulation), and the functions each module provides is as follows
3.1. Data Searching
One can see a GUI as next figure when IsCN executes.
Basically, IsCN provides 3 kind of searching categories. By default, one can search by
protein name, and also to search by pathway or cancer name.
Searching all pathway list
Searching all protein list
If search field is empty, full information that is stored in DB will show up in the screen
Phrase searching is possible for all search types, so is not needed full name for
search. Searching for alias is also possible in case of protein searching.
For example, if one want to search “Beta-trcp”, by only searching “Trcp”,
beta-trcp will be shown in the screen and other aliases(i.e. btrcp) will also be shown in
the list.
Searching Beta-trcp
As shown in example. Protein searching will display every protein that includes
the phrase puts and Cancer searching displays a list of proteins that is related with
certain cancer name that typed. When one picks a protein and pressing 'OK' button,
IsCN connects to DB and displays every pathway(that selected protein is participated)
on the list. Protein selection is disabled when using Pathway searching, because it
will display related pathway list directly on the screen. (See "Searching all pathway list"
above)
Next, after selecting "beta-trcp" on combo-box list and press 'OK' button, pathway
list is shown.
Select pathway(s) (multi-selectable by Ctrl or Shift button), And press "DRAW" button.
3.2. Network Visualization
Visulization module shows pathway network selected from Data searching and able to
check and modify boolean initial value and logic information for simulation.
Visualized wnt pathway, hedgehog pathway Network
Network image will be auto-scaled to fit network into current GUI frame size. One can
configure network size by using Zoom to fit, Zoom in, out button(upper-right side)
Zoom buttons
Each pathway that is drawn at the same time, could be distinguished by
applying different color to each pathway. Moreover, overlapping nodes will choose
mixed color of each pathway, so can be easily detected.(As one can see below)
As one can see in the figure above, Nodes in "B cell receptor signaling
pathway" are displayed in green color, and those in "T cell receptor signaling pathway
are displayed in blue color. and overlapped nodes are displayed in a bluish green color.
Protein
Complex
Pathway
:
Each node that is drawn on the Network viewer window has different shape for its type,
and its description is as below
Interaction information and forms are also defined for each type
: Activation
: Inhibition
: Expression, Binding
: Indirect interaction
And one can also find an information for each node on the Network viewer (by clicking
mouse button(right) )
Check node Information and set boolean initial value in a pop-up window
As a default, boolean logic is OR operation of each node, and one can define it by
his(her) own information. (AppendixB)
IsCN provides various kinds of layouts(how to draw the networks). One can select it in
the menu. Network can be saved as an image file(PNG) or SBML format.
Applying layouts to pathways
Save network image(PNG),
network information(SBML)
SBML file will be named as its saving date and time, and its contents are as shown
below.
To explain SBML format, listOfCompartments has pathway list(those are drawn),
listOfSpecies has description for each node. And boolean initial value will also be saved.
Contens of saved SBML file
In the Visualization section, Network information will be shown in table form. One can
open each table(node, interaction), if he(she) want to check node or interaction
information.
Node Information Table
Interaction Information Table
One can sort Node Information, Interaction Information table by clicking it’s column
name And through File-New function on menu bar, One can search another pathway
without restarting program.
3-3. Boolean Simulation
As mentioned earlier, IsCN could simulate(Boolean) pathway network. Simulation will be
started by simulation – start in menu bar or using Chart(graph) button in toolbar, and new
window for simulation will be opened.
Start Simulation
When simulation button is clicked, Configure simulation window is opened automatically.
Text field in “Simulation Time Steps” sets the length of time slots to simulate.(One step
simulation also provided) and check buttons are nodes those will be displayed in
Boolean graph and State Transition Diagram.
Simulation Configuration window
Initialized Simulation GUI
Simulation will proceed when “A step(F3 as shortcut key)” or “00 steps((F4 as shortcut
key) is clicked. And if one wants to change length of multiple steps, then SetupConfiguration will show you the configuration window shown in previous page again.
And if one wants to initialize simulation values, there are two ways to set initial value
of nodes.
Setup-Initialize-By all Zeros and Setup-Initialize-By selected step.
First one will set all nodes initial value as zero. And second one is used when simulation
is loaded and one wants to set nodes value as specific time step in the “Table”.
Set nodes value as specific time step
“Table” tab shows simulated nodes value as 0 or 1. If you want to see some specific
nodes behavior. See “Graph” and “State Transition Map” also. In those 2 taps, only
nodes those are selected in configure window will be displayed. “Graph” will show
nodes’ Boolean value as chart, and “State Transition Map” will show how selected
nodes are changed from one state to another.
Simulation Result
As in visualization mode, Simulation result could be saved. Each Boolean value will be
saved as *.txt file and State transition diagram will be saved as *.png form.
Menu to save simulation result
Appendix A. Network Viewer _ Network Editing
IsCN V1.0 does not implement “Network Editing”. So it is disabled in Mouse-right click.
It will be implemented in V2.0 to provide a function that can be used to study the effect
of node-deletion(knock-down).
Appendix B. Boolean Simulation _ Simulation Information Setting
In IsCN V1.0, Boolean logic in node Information can be modified by the user using
correct information By correcting operational priority among nodes or incorrect relation
information, User can simulate more precisely. But while correcting operator (And/OR),
there will be a chance of node name changing. If it happens, simulation model might not
be able to recognize it and give an error. To prevent such problems, in next version,
node names will be fixed and unmodifiable