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[DESCRIPTION]
<p>Network science is a cross-disciplinary domain that focuses on the representation, analysis and modeling of complex systems as networks or graphs. In computational biology, Cytoscape is a very popular open source software platform for network modeling and visualization. As an example, Cytoscape can be used to identify disease modules which are defined as connected subnetworks showing mechanistic evidence for a specific phenotype.</p>
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<div>In the context of a new subnetwork identification, it is of interest to have access to <span style="display: inline !important; float: none; background-color: transparent; color: #000000;">measures </span>of connectivity that help to assess the probability that this subnetwork could arise by chance.</div>
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<div>The  <a href="https://github.com/belleau/subnetsim" target="_blank" rel="noopener noreferrer">R subnetsim package</a> uses bootstrapping to test the hypothesis that a specific subnetwork is more connected than randomly generated subnetworks with the same number of nodes.</div>
<div>Three measures of connectivity are validated by the R <strong>subnetsim</strong> package:</div>
<div>  - the number of nodes in the subnetwork including all the first-degree neighbor nodes</div>
<div>  - the number of links in the subnetwork including all the links of the first-degree neighbor nodes<br />  - the number of links in the subnetwork</div>
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<div>The  <a href="https://github.com/belleau/subnetsim" target="_blank" rel="noopener noreferrer">R subnetsim package</a> also offers the possibility to easily graph the results of the simulations.</div>
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<div>This protocol <span style="display: inline !important; float: none; background-color: transparent; color: #40474c;">provides the detailed method of a simulation analysis done on a specific subnetwork. To do so, the global subnetwork, from which the subnetwork is extracted, is needed in SIF format file.</span></div>

[GUIDELINES]
<div><strong>SIF Format Input</strong></div>
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<div>The Simple interaction file (SIF) format is one of multiple formats that Cytoscape can read. For the moment, it is the only format used by the R subnetsim package. SIF file can manually be generated as long as the basic rules as follows. Cytoscape provides information about <a href="http://www.cytoscape.org/manual/Cytoscape2_6Manual.html#SIF Format" target="_blank" rel="noopener noreferrer">SIF Format</a>.</div>
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<div><strong>R software environment</strong></div>
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<div><span style="display: inline !important; float: none; background-color: transparent; color: #444444;"><a href="https://www.r-project.org/" target="_blank" rel="noopener noreferrer">R software environment</a></span> must be installed on the computer that will be used to run the simulation analysis.</div>

[STEPS]
SECTION: Install R subnetsim package version 0.2.1
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SECTION: Load R subnetsim package
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SECTION: Load the global network and the tested subnetwork
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SECTION: Generate the simulated subnetworks
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SECTION: Extract the information from the simulated subnetworks
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SECTION: Plot the results
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