Example Four: Gene Networks


This example demonstrates how to generate gene networks from time-series expression profiles (microarray data).

The Dynamic Signaling Maps module generates gene networks from time-series expression profiles. This tool is most useful when studying a limited number of genes that are known — or suspected — to modulate each other's expression levels. Currently, the maximum number of genes that you can analyze with this module in the internet-based version is twenty and the number of timepoints must be greater than the number of genes.

This example uses a data subset from a classic yeast cell-cycle experiment by Spellman et al. Data file is uploaded to the DSM server where it is analyzed. A control panel is then displayed as shown in the screen shot below:

The DSM system parsed the microarray data, computed potential activations and inhibitions, and stored them internally as numerical values. Blue bars are the distribution graph of negative values (inhibitions) while red bars are the distribution graph of positive values (activations). Green sliders allow you to set thresholds (cutoff values) for the next step where the network will be computed. Values greater than thresholds will account for gene interactions; any other values will be ignored. The larger the absolute value displayed on the abscissa the more likely it is that you are looking at an interaction present in the experimental system being analyzed. The commercial version of Dynamic Signaling Maps has a feature that allows the user to display, in addition to the distribution graph, the gene-to-gene interaction coefficient table (also known as transfer matrix lambda; see a screen shot).

You can drag the sliders to set reasonable threshold values and then click the Move green sliders... bar above the panels to generate the network. A new window is displayed:

The generated network is shown in DSM Language format. Click Copy to copy it to the Clipboard (only works in Internet Explorer) or click File DSML to insert it into your first empty DSML file on the DSM server; you can generate an editable graphical map for your network off the DSM console after you open and translate that file (and, of course, you can also Analyze your network, see Example Two). Click the Preview Network button to preview the network as a two-dimensional diagram, see screen shot below or a Flash object (Flash MX or higher viewer required):

Setting thresholds to different values allows you to control network complexity. Reset clears the uploaded data.

The Overlay Expression add-on displays a 3D animation of the expression data overlaid onto the signaling pathway diagram, see screen shot below, or a Web3D model (VRML 97 plug-in supporting animation required), or a video clip (304KB, MPEG format).

 

In the VRML applet window, you can use the pointer to control the view angle and position; point to any vertical bar to view its corresponding gene name. The number in the lower-left corner is the animation frame number and indicates the time-point for the data being displayed.


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