Help File for eXPatGen

Getting Started and the Main Page
- Navigating to eXPatGen
- Starting the Simulation
Initial Input Form
- Overview
- Environmental Matrix
- Induction Matrix
- Repression Matrix
- Repression Behavior Parameters
- Induction Behavior Parameters
Saveable Input Form
- Overview and How to Use This Form
Final Input Form
- Overview
The Simulator
- Running the Simulator
- Getting a Copy of the Input File
- Saving the Simulation
eXPatGen Output Generation Form
- Overview
- Which Data to Output
- Data Manipulation
- Log Transformation
- Delimiter Between Data Points
- Converion of mRNA Values to Fluorescence Values

Getting Started and the Main Page

Navigating to eXPatGen

To use expatgen type the following link into the location bar of your browser and type enter:
http://www.che.udel.edu/eXPatGen/

Starting the Simulation

Before you start the simulation, you must decide how many gene groups and environmental conditions you want to simulate. A gene group is a set of genes that are induced or repressed by the same set of gene groups as each other. Each environment allows you to change whether a gene is initially turned on or off at the beginning of the simulation. You can also change the gene groups that induce and repress each other for each environment. Click the button when you have decided how many gene groups and environments you need and entered the values into the appropriate text boxes.

The Initial Input Form

Overview

The initial input form is where you will input the gene network into the simulator. The form allows you to specify which genes are initially on in each environment, which gene groups induce others, and which gene groups repress other gene groups. It allows you to tell the simulator how the genes are repressed, and how each inidividual gene group on average responds to an induction factor.

Environmental Matrix

The environmental matrix controls which gene groups are initially expressed for the different environments in the simulator. The gene groups are listed horizontally in the top row. The environments are listed vertically in the far left column. To tell the simulator that a gene is expressed, find the cell that corresponds to the row of the environment and the column of the gene group. Then replace the contents of that cell with the value '1' (without the quotes). If you change your mind change the contents of the cell to 0. For example, to initially turn on gene group 1 in environment 1 and gene group 3 in environment 2 the following matrix would be set:

Environmental Matrix

Each cell represents whether a gene group is initially expressed in the environment. Enter a 1 to signify that it is initially expressed or a 0 to signify it is initially not expressed.

Gene Group 1 2 3 4 5
Env. Condition 1

Env. Condition 2

Induction Matrix

In the induction matrix, the simulator is told which gene groups cause other gene groups to be turned on. The gene groups are listed across the top row. The environments are listed in the far left column. A gene group can be induced by a different gene group for each environment. To signify that gene group 3 is induced by gene group 2 in environment 1, a 2 is entered in the appropriate cell, as seen below:

Induction Matrix

Each box represents a gene group for a specific environment. Enter the number of the gene group that induces that group into the box. A 0 indicates that it is not induced.

Gene Group 1 2 3 4 5
Env. Condition 1
Env. Condition 2

Repression Matrix

In the repression matrix, the simulator is told which gene groups repress other gene groups. The gene groups are listed across the top row. The environments are listed in the far left column. A gene group can be repressed by one other gene group for each environment. To signify that gene group 2 is repressed by gene group 4 in environment 2, a 4 is entered in gene group 2's environment 2 cell as seen below:

Repression Matrix

Each box represents a gene group for a specific environment. Enter the number of the gene group that induces that group into the box. A 0 indicates that it is not induced.

Gene Group 1 2 3 4 5
Env. Condition 1
Env. Condition 2

Repression Behavior Parameters

This box allows a user to determine the rate at which genes are repressed. There are two models available: sigmoidal and saturation kinetics. This selection will affect all of the groups in the simulation. To select the model, click the drop down box and then click the model you would like to use. For each of these models, there are two parameters you can adjust: the time offset at 50% reduction and the speed of response.
- The time offset at 50% reduction determines how long it takes for 50% of the mRNA to be degraded. A larger offset means that more mRNA will be present after repression starts than a small offset.
- The speed of response determines the angle of curvature of the mRNA concentrations. A large angle of curvature will show very little repression until the time offset at 50% reduction is reached, and then show very rapid reduction of mRNA levels just before and after this time. A small speed of response will show a much more gradual reduction in mRNA concentrations. To better visualize the effect of the time offset and the speed of response the following applet is available.

Induction Behavior Parameters for Each Gene Group

This section is used to create a normal distribution of genes for each group based off a mean and standard deviation for each feature. For each group, first select whether you want model the induction of the gene group as sigmoidal or saturation kinetics. Do this by selecting your choice in the drop down menu next to the words "Choose Model". Then, enter the number of genes you would like to generate for this group in the box next to the words "Number of Genes". Next enter the mean and standard deviation of four different parameters into the appropriate boxes. eXPatGen will produce a normal distribution around each of these parameters. The "Relative Gain" boxes control how much more the final equilibrium concentration of mRNA will be above the nonactive gene. The "Time @ 50% Gain" boxes determine how long it will take for 50% of the mRNA to be produced after the gene is induced. The "Speed of Response" determines whether this concentration of mRNA increases gradually (a small speed of response) or rapidly (a large speed of response). The "Baseline Value" boxes indicate the equilibrium concentration of mRNA when the gene is inactive or repressed.

When you are finished entering the values for each group, click the button to continue.

Saveable Input Form

Overview and How to Use This Form

This form is intended to be used as a save point. You can use it to resume an eXPatGen simulation at a later time. However, only the values entered on the previous page will be saved. You can make changes on this page and submit them to run the simulator with the new values. However, if you save using this file the new changes you make on this page will not be saved. To save your work:
- Firefox - Go to the file menu and select the option "Save Page As..."
- Internet Explorer 6 - Go to the file menu and select the option "Save As..."
- Internet Explorer 7 -
To resume your work, double-click the file you saved. Once open, make changes to the file if neccessary and proceed to the bottom of the form and click the button to continue to the final input form.

Final Input Form

Overview

On this page you can adjust the individual gene parameters. You can also save the page using the instructions in the above section. However, changes made to this page will not be saved. They must be saved on the next page. You may edit the Envioronmental, Induction, or Repression Matrices, or the repression parameters. When you are finished adjusting the inidividual gene parameters, press the button at the bottom of the form.

The Simulator

Running the Simulation

The simulation starts at time=0, with the microarray showing the genes initially turned on as red, green, or yellow. To get the next view of the microarray, press the button. Pressing this button causes eXPatGen to advance the specified number of minutes. You can adjust the time interval between the views of the microarray by editing the value in the box next to the button.

Getting a Copy of the Input File

Click the link Input File. Once the new page opens, follow the instructions in the saving an input file section. You can use this input file to restart the simulation.

Saving the Simulation

Once you have traversed over a suitable time period, you can export the data in a variety of formats. Click the eXPatGen Output Generation Form link to begin.

eXPatGen Output Generation Form

Overview

Use this form to output the simulation data in the desired format by selecting the appropriate options below. Click the "Generate Output File" button to produce the text file.

Which Data to Output

Select the appropriate radial button to inidicate which environment you would like to produce data for.
- Ratio of Condition 2 (red) to Condition 1 (green) - divide the mRNA concentration of the second environment by the mRNA concentration of the first environment.
- Simulated Condition #1 Only (green) - output the mRNA concentrations of only the first environment.
- Simulated Condition #2 Only (red) - output the mRNA concentrations of only the second environment.

Data Manipulation

- Transpose the Data - Select yes to have the genes listed across the top row and the times on the far left column. No switches them.
- Convert By Absolute Value - If yes, takes the absolute value at the end.

Log Transformation

Select which type of log you would like to take on the mRNA concentrations, if any.

Delimiter Between Data Point

Select how cells are separated in the output file: with a comma, tab, or space.

Conversion of mRNA Values to Fluorescence Values

Allows you to output the mRNA concentrations as fluoresence values. If you choose to, you can define how the fluoresence values are calculated for the red and green dots. Enter the mean and standard deviation into the appropriate text boxes, and enter the size of the spot area you would like.

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