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Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

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5.10 Glioblastoma Pathway Construction Methods<br />

Figure 5.7: Schematisation <strong>of</strong> a typical Cytoscape network look, with nodes and<br />

edges representing proteins and the type <strong>of</strong> interaction between them, respectively.<br />

The colour and shape <strong>of</strong> the nodes can be attributed to different characteristics <strong>of</strong> the<br />

proteins, such as their family, enzymatic activity, post-translational modifications,<br />

etc. The colour and shape <strong>of</strong> the edges can be attributed to the type <strong>of</strong> interactions<br />

between proteins, such as activating, inhibiting, coenzymatic, etc. In this example<br />

protein A and B interact to form a complex that activates protein D, also repressed<br />

by protein C, that once active can go ahead and activate protein E.<br />

A series <strong>of</strong> pre-defined "layouts" available in Cytoscape, i.e. algorithms that<br />

automatically lay a network out by generating arrangements <strong>of</strong> nodes and<br />

edges that either make it look a specific way, such as the circular, grid and<br />

hierarchical layouts, or use the attribute information as a guide, such as the<br />

attribute circle, degree sorted circle, force-directed, group attributes layouts.<br />

For our purposes we used the edge-weighed force-directed layout, also known<br />

as "biolayout" that, once generated, was manually re-adapted to obtain a best<br />

fit for image generation. In order to graph the network, the edge-weighed<br />

force-directed layout, or biolayout, uses an algorithm that minimises the en-<br />

ergy <strong>of</strong> the model by starting with an initial layout, where the positions <strong>of</strong> the<br />

nodes are randomly assigned. Then, in every iteration, the algorithm tries to<br />

improve the layout according to the energy model using the first derivation <strong>of</strong><br />

the energy function to compute a direction and a distance for the movement<br />

<strong>of</strong> each node. Since the graphs generated are large, the minimising algorithms<br />

do not carry a high complexity per iteration value. The algorithm <strong>of</strong> Barnes<br />

and Hut [42] is used in Cytoscape’s biolayout for this purpose.<br />

The glioblastoma pathway was constructed manually by integrating the infor-<br />

mation on nodes (genes) and edges (types <strong>of</strong> interactions between genes) from<br />

a variety <strong>of</strong> glioblastoma pathways found in the literature with the purpose <strong>of</strong><br />

115

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