MBs are SHH subgroup tumours and Igf2 is a key network associated gene.
a-b. Projection of four sub-group specific metagenes
derived from 108 human primary MB expression profiles (Training Set)
onto MB mouse model expression profiles (Test Set) using Non-negative
Matrix Factorisation (NMF). a. Heatmaps showing expression
of metagenes across human tumours (training; left panel) and expression
of metagenes across murine tumours (test; right panel).
b. Pseudo-plot of NMF projections coloured according to
confident MB sub-group classification of murine tumours using metagene
expression values. This unsupervised analysis shows that the majority of
Ptch mouse model samples recapitulate the expression
profiles of primary SHH MB. c. Box and whisker plots
showing relative Igf2 expression assayed by Real Time PCR
(for details, see Methods): Left Panel - tumours with inserts in 1 or
more network CIS gene versus tumours with no inserts; Right Panel -
Igf2 expression in tumours with 1 or more insertions
in Nfia versus all other tumours with inserts in at least
1 network CIS gene. Boxes represent the 25th to
75th percentile, with median values shown as solid
lines. Whiskers represent 95th percentile, and outliers are
shown individually. d-e. GSEA plots for human tumours
ranked by metagene score (left panels) and mouse tumours ranked by fold
change of expression in tumours with network hits compared to
predisposition control MBs not exposed to mutagenesis (right panels).
ES-Enrichment Score, RM-Ranked list Metric.
d. Lein_Neuron_Markers. Human NES=2.15 p<0.001, Mouse
NES=-2.24 p<0.001. e. KEGG_Ribosome. Human NES=-3.00
p<0.001, Mouse NES=2.59 p<0.001.