PathwayOracle is a software system that provides tools for analyzing cellular signaling networks. In this tutorial, you will learn how to launch PathwayOracle and use its main features.
If you installed PathwayOracle from source, after following the installation instructions, run the python script 'run.py'. If you downloaded the bundled application, double-click on the application. PathwayOracle will launch.
Upon starting up, PathwayOracle will prompt you for a signaling network. In this tutorial, we use a subsection of the EGFR network: sram.ewe. Download this file and open it through the PathwayOracle dialog box. After clicking Open you will be presented with a network diagram. This is the main window of PathwayOracle.
PathwayOracle allows the user to query for paths in the network that connect two specific proteins. In the menu, select Paths -> Compute Paths. A dialog box will appear prompting you for a source and destination. Use the names of proteins in the currently loaded network.
To find the path between IRS and mTOR/rictor, enter IRS as the source and mTOR/rictor as the destination. Click the Compute button. After computing the paths, a path interrogation window will appear.
From this window, you can select individual paths, groups of paths, proportional paths, and inverse paths. Any paths selected in the currently active path interrogation window will be highlighted in the main window.
PathwayOracle provides an implementation of a novel non-parametric method that simulates the response of the network to a given experimental condition. The simulation can be run in one of two ways, both of which can be found under the Dynamic Analysis menu item.
The New Tokenized Simulation simply simulates a single experimental condition. In this case, the simulation dialog takes as input the number of runs to conduct, the number of time blocks for which the simulation will run, and what molecules are fixed (or known to be) high or low in the experimental condition. The New Differential Simulation simulates two different experimental conditions and quantifies the difference in the response of the network. In this case, the dialog requires that the high/low molecules be specified for both experimental conditions.
After running the simulation, you will be returned to the original network view and a new window will popup with an empty graph. To the right of the graph is a checkbox list for each molecule in the network. By selecting a molecule, you add it to the graph. The graph displays the number of tokens assigned to a given molecule for each time block evaluated during the simulation.
You can return to this view at any time by using the Marking Manager in the Window menu. The Marking Manager will appear.
In the upper part of the manager, you will see the name of the simulation you ran. Clicking on it will display the properties of the marking series (the output of the simulation). To view the actual predicted responses of the molecules to the experimental condition, click the Inspect button. In the inspector view, you can add plots of different proteins by checking the boxes by their name. By adding multiple plots you can visualize the predictions of the simulator.