Transcriptional Characterization of Glioma Neural Stem Cells Diva ...

7.5 Glioblastoma Pathway Analysis Results
Figure 7.7 shows the integrated pathway in its default colours, without any
overlaid expression data that would colour the gene nodes. Sections pertaining
to different pathways are coloured in blue if the pathways are glioblastoma-
specific or cancer-specific and orange if they reflect the cross-talk between the
three well-known pathways commonly affected in glioblastoma. The colour,
line and endpoints of the edges represent the type of interactions between the
nodes: activation (solid, green, arrow point), transcriptional activation (solid,
green, diamond point), tentative activation (dashed, green, arrow point), inhi-
bition (solid, red, T point), transcriptional inhibition (solid, red, delta point),
includes (solid, black, circle point), becomes (solid, black, top half arrow point),
simple interaction (solid, grey, no endpoint), leading to (dashed, grey, arrow),
lets in (dashed, grey, no endpoint). The shape of the node represents the type:
gene (round), complex (hexagon), family (hexagon), molecule (fee), process
(round rectangle). Finally, the beige colour distinguishes genes (grey if not
overlaid with colour-coded expression data) from non genes (beige). All the
interactions described by the pathway can be found in Appendix D.1.
In order to ensure that every single interaction described in the pathway had
been experimentally validated I checked every one of them in the interactions
databases described in detail in the Methods section, such as BioGrid [62] and
Intact [205]. Thus, this glioblastoma pathway is a representation of physically
interacting proteins at work in the specific disease context. When the interac-
tion needs to occur with chromatin to describe the regulation properly, such as
in the case of a transcription factor, either a node named "DNA" is described
as one of the two interactors, or a special edge named "activates transcription
of" or "inhibits transcription of" - that can be identified by the diamond or
delta endpoint, respectively - connects the two interactors. The entire pathway
can be recreated from the list of interactions and interactors described in Ap-
pendix D.1, but an editable version - with extension CYS - can be downloaded
from www.ebi.ac.uk/~diva/GBM-pathway.cys, where the latest and previous
versions of the pathway are available. The CYS extension allows the pathway
to be viewed and/or edited with any network editing software, such as Cy-
toscape [451]. The availability of the pathway for download and use by other
researchers, as well as its constant curation, attempts to address one of the
four main shortcomings of already existing GBM pathways: the unavailability
of formats other than images. Hopefully this resource will now be used by all
the researchers who want to overlay expression data on a new comprehensive
integrated GBM pathway to observe changes in the wider disease context.
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