Figure 5

Ptch^+/- 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 25^th to 75^th percentile, with median values shown as solid lines. Whiskers represent 95^th 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.