Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

5.10 Glioblastoma Pathway Construction Methods
by Colman et al [105] was taken. The normalised expression values xij, where i
represents the gene and j the sample, were first standardised to be comparable
between genes by subtracting the mean across samples and dividing by the
standard deviation, thus creating a matrix of z-scores:
zij = xij − ¯xi
SD(xi)
(5.8)
Using a set U of nU genes up-regulated in GNS lines and a set D of nD genes
down-regulated in these cells, we then computed a GNS signature score sj for
each sample j by subtracting the mean expression of the down-regulated genes
from the mean expression of the up-regulated genes:
sj =
i∈U
zij
nu
−
zij
nD
i∈D
(5.9)
IDH1 mutation calls for TCGA samples were obtained from Firehose data run
version 2012-07-07 [143] and data files from the study by Verhaak et al updated
2011-11-28 [408].
5.10 Glioblastoma Pathway Construction
The pathway map was created in Cytoscape 3.0 [451]. Cytoscape is an open-
source platform for complex network analysis and visualisation of network
data, such as molecular interaction networks or biological pathways, that can
be integrated with annotations, gene expression profiles and any other type
of useful data. Cytoscape is available for download at www.cityscape.org. In
a Cytoscape network nodes represent objects, i.e. proteins, and connecting
edges represent relationships between objects, i.e. a protein’s physical inter-
action with another protein. Once this basic network is laid out, attributes
can be assigned to nodes and edges to help the visualisation of categories of
objects and types of relationships, respectively (Fig 5.7). Cytoscape networks
can become extremely complex as layers of attributes are applied to nodes and
edges in the form of different colours, shapes, thicknesses and other graphical
features that end up representing an ever-increasing amount of biological infor-
mation pertaining to that network. Finally, cytoscape-generated networks can
be analysed with the use of "plugins", pieces of independent software devel-
oped for specific applications on Cytoscape such as graph analysis, clustering,
ontology analysis, etc. All plugins can be found at aps.cytoscape.org.
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