Predictive (downstream; "after") analysis allows researchers to answer questions such as: "What is the effect on the signaling pathway of the activation/increase in the amount of, or inhibition/decrease in the amount of, a particular factor?"

Postdictive (upstream; "before") analysis allows researchers to answer questions such as: "What signaling pathway events can result in the activation/increase in the amount of, or inhibition/decrease in the amount of, a particular factor?"

Let us first recall the last pathway in Example One (see it in PDF format):

In the left pane of the Analysis dialog there is a list of "triggers" (molecules, complexes, and other factors) parsed from the signaling pathway above. Select one item on this list to run a pathway analysis; your selection is the factor that you know has undergone a particular state change (activation, inhibition) and you wish to determine either its downstream effect or its potential upstream cause. To that purpose you can perform an "after" or "before" signaling pathway analysis, respectively, while the state of the "trigger" you select can be "activated/increased" or "inhibited/decreased":

For instance, to answer the question "What is the downstream effect of CD40-ligand binding to CD40 in the cytoplasmic membrane?" you would select (CD40L[CYTOMB],CD40[CYTOMB]) and the After and activated options. After you click the Analyze button the right panel changes to show the state of downstream elements in the signaling pathway when the amount of active CD40 + CD40-L complex increases in the cytoplasmic membrane:

This analysis shows that potential effects of CD40 + CD40-L complex activation in the cytoplasmic membrane include, but are not limited to, the activation of NF-kB in the cytoplasmic membrane and the activation of CD20 and CD23 in the cell nucleus.

Alternatively, to answer the question "What are the potential causes of IRF4 inhibition/decrease in the cell nucleus?" you would select IRF4[NUCL] and the Before and inhibited options. After you click the Analyze button the right panel changes to show the state of upstream elements in the signaling pathway when nuclear IRF4 activity is decreased:

This "what-if" analysis shows that potential causes of IRF4 decrease/inactivation in the cell nucleus include, but are not limited to, a decrease in cytosolic LPS, the inhibition of STAT6 phosphorylation in the cytoplasmic membrane, and the activation of PRDI-BF1 in the cell nucleus.

The Undetermined category contains items whose state cannot be determined based on the current data in the signaling pathway. Reasons for this type of situation are discussed in the online Help System. The commercial version of Dynamic Signaling Maps has an enhanced analyis algorithm, which minimizes the number of items in this category.

To display an analysis report in printer-friendly format you can click the Report button.