Instruction for CADLIVE Simulator

Contents
1. Login ..........................................................................................................................................1
2. User registration.........................................................................................................................2
3. DB maintenance ........................................................................................................................3
4. File interface ..............................................................................................................................55. Simulator....................................................................................................................................7
5.1 Start screen ..........................................................................................................................7
5.2 Upload of data for regulator-reaction equations ...................................................................7
5.3 Selection of conversion methods..........................................................................................8
5.4 Editing mathematical model .................................................................................................95.5 Selecting analysis types .....................................................................................................105.6 Input for control data .......................................................................................................... 11
5.7 Input of parameters ............................................................................................................12
5.8 Result indication .................................................................................................................14
5.9 Database registration .........................................................................................................15
5.10 Data download .................................................................................................................15
5.11 Selecting a mathematical model.......................................................................................16
5.12 Selecting job (Mathematical model) .................................................................................17
5.13 Direct edition of mathematical equations..........................................................................18
6. Graph visualization ..................................................................................................................19
6.1 Setting graph data ..............................................................................................................19
6.2 Set for graph display ..........................................................................................................20
6.3 Graph display .....................................................................................................................21
6.4 Details of graph ..................................................................................................................21

1. Login
Following

theinstallationoftheCADLIVE

Simulator,open

http://kurata01.bse.kyutech.ac.jp/TEST/Life/index.html on a PC browser to display the screen
shown in Fig. 1-1. Input the user name, subsequently his/her password to start up simulation.

If there is anything wrong with calculation and you want to kill your job, access thesite of http://kurata01.bse.kyutech.ac.jp/TEST/Life/kill, and push the kill simulator
button.

Fig. 1-1 Startup screen1

2. User registration
Click the [User Admin] button under the left side of the screen to display the screen shown in Fig.
2-1. This operation is restricted to the persons who are registered as administrators. Registration
is carried out by inputting the user name, his/her password, and admin/user.

Fig. 2-1Screen for registering users
The persons who have the admin account are able to delete any accounts and their data, butones with the user account are not able to access the other accounts.

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3. DB maintenance
Click the [Database Maintenance] button, the screen transits as shown in Fig. 3-1

Fig. 3-1 Database maintenance
Clicking the [Delete] button displays the lists of registered data (Users: their own data, Admin:
the data of all the accounts), as shown in Fig.3-2. Users are able to delete the data by clicking
the corresponding checkbox and by clicking the [Delete] button. Users save their data at theirconvenient time during the process of simulation.

Fig. 3-2 Mathematical model data
Clicking the [Modify] button displays the list of the registered data as shown in Fig. 3-3, which
is similar to that as shown in Fig.3-2.

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Fig. 3-3 Selection for mathematical model data
Clicking the data title that users want to modify displays the new screen shown in Fig. 3-4,
where they edit their models. Clicking the [Save to DB] button registers the modified data on thedatabase. Notice that users have to learn the instruction of the simulator to edit their data
manually.

Fig. 3-4 Editing mathematical model data

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4. File interface
Clicking the [File Interface] button changes the upper region of the screen as shown in Fig. 4-1,
where users change their data between the database and their PC.

Fig. 4-1File interface
Clicking the [Upload] button displays the screen (Fig. 4-2), where users are able to register
their data.

Fig. 4-2 Upload data from a local PC5

On the other hand, clicking the [Download] button displays the list of the registered data, whereusers see the content by clicking the data title and download it to their PC.

Fig. 4-3 Select data to download

65. Simulator
5.1 Start screen
Clicking the "Simulator" button changes the upper region of the screen as shown in Fig.5-1.

Fig. 5-1Startup for simulator
5.2 Upload of data for regulator-reaction equations
On the startup screen (Fig. 5-1), clicking the [Regulator-reaction equations] button displays thescreen (Fig. 5-2), where users select the data file for regulator-reaction equations from their PC.
Users are required to click the buttons within the white screen, not to carelessly click the buttonsof the browser.

Fig. 5-2 Select of regulator-reaction equation data file7

5.3 Selection of conversion methods
Selecting an appropriate data file displays the screen (Fig. 5-3), where users choose theconversion methods with respect to gene-protein layer and metabolic layer, respectively.
The conversion method can be selected out of the following methods:
Gene-Protein layer:- CMA- TPP_STEADYSTATE_1- TPP_STEADYSTATE_2- TPP_RAPID
Metabolic layer:- GMA- MM- SAME_AS_GENE-PROTEIN

Fig. 5-3 Selection of conversion methods
Following the selection of the conversion methods, clicking the [Confirm] button displays theconfirmation screen that is similar to Fig. 5-3.

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5.4 Editing mathematical model
Clicking the [Submit] button on the confirmation screen (Fig. 5-3) parses the regulator-reaction
equations, converting them into the mathematical model according to the selected conversion
method. The resultant mathematical model is displayed on the screen (Fig. 5-4).

Fig. 5-4 Mathematical models
This screen mainly has seven parts: the header, the definition of constant players, the definitionof variables, the definition of the employed parameter labels, the definition of kinetic parameters,
the definition of intermediate mathematical expressions, the definition of algebraic equations, andthe definition of differential equations.
Clicking the [Regulator-reaction eqs.] button displays another window for showing
regulator-reaction equations. Clicking the [Parameter info.] button shows the parameter
information. The [Download] button enables users to download various data files to their local PC.
Clicking the [Confirm] button displays the confirmation screen. If there is no problem, click the[Submit] button. The detailed instruction is referred in the documents regarding checkdae.

95.5 Selecting analysis types
Clicking the [Submit] button on the confirmation screen displays the screen (Fig. 5-5), whereusers select the analytical type for a mathematical model.

Fig. 5-5 Selection of analytical types
As "Analsys type", users can choose either “Dynamic” or “Steady-state”. “ Dynamic” simulates
the time evolution of the concentrations by calculating differential and algebraic equations, and“Steady-state” calculates the concentrations at steady state by solving algebraic equations. The
checkbox of "Parameter survey" determines if the simulator surveys the parameter space.
Checking the checkbox of "Parallel calculation" carries out parallel calculation that employs theMessage Passing Interface (MPI). Notice that the checkbox of "Parallel calculation" cannot be
selected prior to checking the parameter survey.
The checkbox of "Use S-system", which employs S-system differential equations, appears only
under the condition that the steady-state concentrations have been solved.

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5.6 Input for control data
Clicking the [Submit] button on the selection screen for analytical types displays the screen for
input of the control data (Fig. 5-6). Following data input, clicking the [Confirm] button shows theconfirmation screen. The detailed explanation is described elsewhere.

Fig. 5-6 Set control data for simulation

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5.7 Input of parameters
Clicking the [Submit] button on the confirmation screen for setting control data for simulation
displays the new screen (Fig. 5-7-1), where users input the values for the kinetic parameters andinitial values. The detailed explanation is described elsewhere.

Fig. 5-7-1 Setting parameters and initial values
The [Initial val.] button, which does not appear on the screen until the “Save for input” button iscarried out by the previous simulation, displays the final values of the time course data that havebeen simulated. Those values are copied and pasted as the initial values on the file for setting
parameter and initial values. The initial values is required for solving the steady state
concentrations of the algebraic equations
Clicking the [Upload & merge File] displays the screen (Fig. 5-7-2). After clicking the[Confirmation] button, clicking the [Submit] button transit to the confirmation screen.

12Fig. 5-7-2 Uploading data from a local PC
The parameter file that has been made according to the rules of the simulator is input in the boxof "FileName". Clicking the [Upload] button displays the previous screen (Fig. 5-7-1), where theparameters are automatically input from the uploaded file. Checking the box of "Upload blankonly" does not update the existing parameters and initial values. Checking the box of "Upload all"replaces all the data by those of the uploaded parameter file.

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5.8 Result indication
Clicking the [Submit] button on the confirmation screen starts simulation and displays the results(Fig. 5-8).

Fig. 5-8 Results
When the simulation is successfully completed, the results are shown on the screen, whichcontains the log including the calculation time. The final runs of time evolution and steady-state
analysis are saved as the results, respectively. When simulation fails, the log is shown first,
subsequently displaying the input file.
The button of [Save for input] stores the concentrations at the final time or the steady state
concentrations, which can be used for the subsequent analysis of the time-evolution dynamics
and the steady state analysis, respectively. Notice the [Initial val.] button (Fig. 5-7-1).
Clicking the [Graph] button, which appears when the time-evolution of "dynamic" is simulated
successfully, opens the window that indicates the results.

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5.9 Database registration
The screen for indicating the results (Fig. 5-8) has the [Registration] button. Clicking the[Registration] button shows the final confirmation screen that has also the button of [Registration].
Clicking it displays the screen for "Insert New Data from the Simulator" (Fig. 5-9). Following
inputting the title and comments, clicking the [Save to DB] button saves a series of simulation
data as a mathematical model in the database.

Fig. 5-9 Registration of data in database
5.10 Data download
The screen for results (Fig. 5-8) also has the [Download] button. Clicking it displays the download
screen (Fig. 5-10)

Fig. 5-10 Download
The data files that have been built are listed. The clicked files are downloaded to a local PC.

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5.11 Selecting a mathematical model
Clicking the [Math model data] button on the "Start" screen (Fig. 5-1) displays the screen for"Select Data to Simulate" (Fig. 5-11-1).

Fig. 5-11-1 Selection of a mathematical model
Clicking the title displays the content of the data, as shown in Fig. 5-11-2.

Fig. 5-11-2 Confirmation of a mathematical model

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5.12 Selecting job (Mathematical model)
Clicking the [Go Simulator] button on the "Confirmation Data for Simulation" displays the newscreen (Fig. 5-12)

Fig. 5-12 Selection of a job
Fig. 5-12 shows three choices, when a mathematical model has been registered after thesimulation was completed. If simulation has not been completed, this screen indicates only theabove two choices.
Go to [Edit User Functions].

:jump DAE editing screen (Fig. 5-4)

Go to [Select Analysis Type].

:jump Calculation method selection screen (Fig.5-5).

Go to [Results].

:jump the result screen (Fig.5-8).

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5.13 Direct edition of mathematical equations
On the "Start" screen (Fig. 5-1), clicking the [Direct input] button displays the screen (Fig. 5-13).
Following the input of a title and comment, clicking the [Submit] button displays the screen forindicating mathematical equations (Fig. 5-1), where the identification lines exist, but no data iscontained. Users can make mathematical equations according to the rules of the simulator, which
is described elsewhere (Commentary for PARSEDAE).

Fig. 5-13 Direct input of a mathematical model18

6. Graph visualization
6.1 Setting graph data
Clicking the [Graph] button displays the window of "Set Graph Data".

Fig. 6-1 Setting graph data
Fig. 6-1 shows the results of the parameter surveys, where the pulldown menu is used forselecting a case of the simulation. Selecting a case from this pulldown menu, clicking the [Select]button turns the blue characters to the values for the selected case.
The right hand side of the screen defines the definition of data that will be plotted on a graph,and can indicate five series of labels and expressions. As default, y1 – y5 and y[1] – y[5] are set
as labels and expressions, respectively. Empty labels and expressions are not allowed. The
variables y[i], calculation symbols +, -, X, /, parentheses (,), and time T are allowed to be used fordescribing the mathematical expression. After setting them, click the [Submit] button.

196.2 Set for graph display
Clicking the [Submit] button on the screen for setting graph data (Fig. 6-1) displays the screen(Fig. 6-2), where the scaling factor and the regions of the X-axis and Y-axis are automaticallycalculated based on the expression and the minimum/maximum values to visualize the fivetime-evolution well. The left hand side of the lower screen shows the maximum and minimum
values, and the changing ratio provided by:(Maximum - Minimum) / Max (|Maximum|, |Minimum|) X 100.
Users are able to change the labels, the scaling factors, and the color of the lines.

Fig. 6-2 Setting graph data
Checking the checkbox of “not draw” omits its time evolution from the graph. Clicking somecheckboxes of “not draw” disables the [Draw graph] button, instead enables the [Rre-calc] button
to work. The button [Re-calc] recalculates the scaling factors and the regions for the X/Y-axises.
The table on the lower screen is set for the X/Y-axises. X indicates time, and Y theconcentrations of variables.
In the above example, the label of the X-axis is Time [x 100 sec], where the numerical label isfrom 0 to 1.0 at the interval of 0.1. If users want to change the label: the numerical label is from 0to 100 at the interval of 10, they set the scaling factor, the maximum and the tick increment as 1,100, and 10, respectively. The X label becomes Time [sec]. The unit factor is the scaling factor
for unit. For example, the [msec] label is changed to the [sec] label by multiplying 0.001 as thescaling factor.

206.3 Graph display
Clicking the [Draw graph] button on the screen for setting a graph (Fig. 6-3) displays the resultsof time-evolution data.

Fig. 6-3 Graph display
The [no legend] button omits the legends. The [Set details] button is able to change the color ofthe graph and other graph expressions.
6.4 Details of graph
Clicking the [Set details] button displays the window (Fig.6-4). Users can change the style of thegraph by inputting the value in the boxes. The values of the graph size and the location of thelegends are determined by using pixel units. The location of the legend is determined by thecoordinate of the left and upper legend

Fig. 6-4 Detailed setting for a graph21