Fig. 10: Confirmation of proteome subtypes and differential feature conservation in an independent biological FFPE dataset. | Nature Communications

Fig. 10: Confirmation of proteome subtypes and differential feature conservation in an independent biological FFPE dataset.

From: Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level

Fig. 10

A Clinical sample information with proteome subtype assignments using ACF based classification94 (B) PCA, based on proteins found in ≥70% samples, illustrating the separation of proteome MB subtypes (source data file has been provided). C Protein abundances of established biomarkers WNT and SHH biomarker FLNA (nWNT = 3, nSHH = 9, nOthers = 18, two-tailed, unpaired t-test, ppWNTvsothers = NS, ppSHHvsothers < 0.001), WNT biomarker CTNNB1 (nWNT = 3, nOthers = 27, two-tailed, unpaired t-test, ppWNTvsothers = NS.) and SHH biomarker GAB1 (nSHH = 9, nOthers = 21, two-tailed, unpaired t test, ppSHHvsothers < 0.001, data are represented as mean values ± SD). D Significant higher abundance of TNC (npWNT = 3, nOthers = 27, two-tailed, unpaired t-test, ppWNTvsothers < 0.0001) and PALMD (npG3myc = 3, npOthers = 27, two-tailed, unpaired t test, ppG3mycvsothers < 0.01) in pWNT and the pG3myc subtype, respectively. Data are represented as mean values ± SD. E Correlation plot displaying mean Pearson correlation per subtype between the integrated cohort and the biological validation cohort. F Hierarchical clustering of biological validation cohort samples with samples from the main cohort (Pearson correlation and ward.D2 linkage). G Heatmaps showing mean protein abundance for the top hit gene sets enriched in the transcriptional (top) and synaptic profile (bottom). H Bar plot displaying proteome subtype-specific Pearson correlation calculated for matched samples between proteins and CpG sites (r > 0.7, n = 29, total number of samples having both DNA methylome and proteome data, 5880 proteins and 549,089 CpG sites). The number of proteins correlating with CpG site of their own gene are shown in color.I Left: Heatmaps for Mean protein abundancies, gene expression values and methylation at CpG sites for all components of the tailless complex polypeptide 1 ring complex/Chaperonin containing tailless complex polypeptide 1 (TriC/CCT) per proteome subtype in matched cases (n = 29, npWNT = 3, npSHHt = 8, npSHHs = 2, npG3 = 3, npG3myc = 3, npG4 = 11) samples having both DNA methylome and proteome data). Middle: Quantification (two-tailed, unpaired t test, data are presented as mean values ± SD) Right: p values when comparing subtypes (ppWNTvspSHHt <0.0001, ppWNTvspSHHs = NS, ppWNTvspG3 < 0.0001, ppWNTvspG3myc < 0.0001, ppWNTvspG4 < 0.001, ppSHHtvspSHHs < 0.001, ppSHHttvspG3 < 0.001, ppSHHtvspG3myc < 0.0001, ppSHHtvspG4 < 0.01, ppSHHsvspG3 < 0.001, ppSHHsvspG3myc < 0.0001, ppSHHsvspG4 < 0.05, ppG3vsG4 < 0.01, ppG3vspG3myc < 0.0001, ppG4vspG3myc < 0.0001). n represents biologically independent human samples. NS = not significant.

Back to article page