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Elementary Flux Mode Plug-In

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The Elementary Flux Mode Plug-In equips Omix with the ability to compute elementary flux modes of metabolic networks. An elementary flux mode (EFM) is a minimal set of fluxes (reactions) connecting a network input with an output. The EFM plug-in computes all possible flux modes meaning all minimal set between all inputs and all outputs. The result can be reduced by picking relevant fluxes. Individual modes can be visualized in the network diagram. The information provided by the EFM analysis helps to understand cellular objectives for the overall metabolic network.

Internally, the Elementary Flux Mode Plug-In uses efmtool by ETH Zurich for the EFM computation.

Using the Plug-In

You can start computation of a network's flux modes by pressing the menu entry "Extras -> Compute Elementary Flux Modes":

EFM entry in the 'Extras' menu
EFM entry in the 'Extras' menu

1.2. Configuring the Computation

Configuring EFM computation
Configuring EFM computation


Now, a configuration dialog appears, where you can specify the settings for the EFM computation. Here, you can define the numeric arithmetic and normalization. Furthermore, you can specify, whether the computational procedure shall be outsourced in a separate process and how much parrallel thread shall be used to a maximum.

Advanced configuration
Advanced configuration


If you are familiar with efmtool you can also configure advanced options. Here, you can specify the adjacency enumerator algorithm, compression mode as well as generator algorithm. The "Help" button allows you to display contextual information about the individual options. We strictly recommend to use the default settings for EFM computation which can in any case be restored by pressing the "Reset" button. For more information about the different configuration options refer to the documentation of efmtool.

By pressing the "Continue" button, the computation of flux modes is performed on the given network stoichiometry. Depending on the network size, this process can take very long. The progress of the computation can not be displayed because efmtool does not provide information about the computational progress. However, in any case, you can abort the computation by pressing the "Cancel" button.

Progress dialog while computing EFMs
Progress dialog while computing EFMs

1.3. Results

After successful computation, the EFM results are displayed in a tabular sidebar which usually appears immediately at the bottom of the main window. If this sidebar is initially invisible due to certain reason, you can activate it by selecting menu entry "View" -> "Sidebars" -> "EFM Results".

EFM result sidebar
EFM result sidebar

The "EFM Results" sidebar shows a table in which every row represents an elementary mode of the network. The individual columns represent the fluxes (reactions) of the network. If a value in a row is not equals zerro, the corresponding flux belongs to the flux mode represented by the row. The EFM result can be exported to CSV by selecting the "Save As..." button.

1.3.1. Reduction

It is possible to further reduce the amount of flux modes displayed in the table. Therefore, the table header contains a checkbox in each column:
  • By default, this checkbox shows ah either/or state meaning that the flux can be both, zerro or not zerro.
  • Check the box to exclude all elementar modes where the corresponding flux is zerro.
  • Uncheck the box, to exclude all elementary modes where the flux is not zerro.

either/or: EFM6.png checked: EFM7.png unchecked: EFM8.png

1.3.2. Visualization

By selecting an infividual row, the corresponding elementary mode is visualized in the network diagram. Therefore, all reactions belonging to the mode (and their connections) are highlighted as depicted:


1.3.3. Custom Visualization

You can extend the way, elementary flux modes are visualized, by own OVL code. Therefore, extend the definition of the Reaction type by a method called "visualizeEFMValue(var,var)" realizing the visualization and optionally a reset method called "resetEFM()":

extend Reaction{
    function visualizeEFMValue(var absoluteValue, var relativeValue){
		//...
    }

    function resetEFM(){
		//...
    }
}


The first parameter of function "visualizeEFMValue(var,var)" is the absolute value of the flux in the result set, the second parameter is the relative value in ranges between -1 and 1.
All changes to the visual appearance of the diagram that are done in "visualizeEFMValue(var,var)" should be reset to the default values in "resetEFM()".

Instead of using JavaScript syntax, you can also use Java syntax:

void visualizeEFMValue(double absoluteValue, double relativeValue){
	//...
}


More information about how to use OVL for data visualization can be found in the Omix User Manual.
A worked example for visualizing flux modes is given here: EFM-Visualization.ovl