Validation of Whole Genome Methylation Profiling Classifier for Central Nervous System Tumors

Figure 1Clustering of 2801 reference central nervous system (CNS) tumor samples using t-Distributed Stochastic Neighbor Embedding (t-SNE) dimensionality reduction. Only the top 32,000 most variable probes across samples were utilized for t-SNE analysis. Methylation class labels point to the corresponding group centroid coordinates. Methylation classes are color-coded according to sample histology. Control tissues are represented in gray; hematopoietic tumors in dark purple; nerve tumors in beige; mesenchymal tumors in pink; sellar tumors in cyan; melanocytic tumors in dark blue; ependymomas in red; glioneuronal tumors in orange; isocitrate dehydrogenase (IDH)-mutated gliomas in yellow; choroid plexus tumors in brown; pineal region tumors in mint green; glioblastomas in green; and other gliomas in violet. Abbreviations represent the following methylation groups: A_IDH, astrocytoma; A_IDH_HG, high grade astrocytoma; ANA_PA, anaplastic pilocytic astrocytoma; ATRT_MYC, MYC; ATRT_SHH, SHH; ATRT_TYR, TYR; CHGL, methylation class chordoid glioma of the third ventricle; CHORDM, methylation class chordoma; CN, methylation class central neurocytoma; CNS_NB_FOXR2, methylation class CNS neuroblastoma with FOXR2 activation; CONTR_ADENOPIT, methylation class control tissue, pituitary gland anterior lobe; CONTR_CEBM, methylation class control tissue, cerebellar hemisphere; CONTR_HEMI, methylation class control tissue, hemispheric cortex; CONTR_HYPTHAL, methylation class control tissue, hypothalamus; CONTR_INFLAM, methylation class control tissue, inflammatory tumor microenvironment; CONTR_PINEAL, methylation class control tissue, pineal gland; CONTR_PONS, methylation class control tissue, pons; CONTR_REACT, methylation class control tissue, reactive tumor microenvironment; CONTR_WM, methylation class control tissue, white matter; CPH_ADM, methylation class craniopharyngioma, adamantinomatous; CPH_PAP, methylation class craniopharyngioma, papillary; DLGNT, methylation class diffuse leptomeningeal glioneuronal tumor; DMG_K27, methylation class diffuse midline glioma H3 K27M mutant; EFT_CIC, methylation class CNS Ewing sarcoma family tumor with CIC alteration; ENB_A, methylation class esthesioneuroblastoma, subclass A; ENB_B, methylation class esthesioneuroblastoma, subclass B; EPN_MPE, methylation class ependymoma, myxopapillary; EPN_PF_A, methylation class ependymoma, posterior fossa group A; EPN_PF_B, methylation class ependymoma, posterior fossa group B; EPN_RELA, methylation class ependymoma, RELA fusion; EPN_SPINE, methylation class ependymoma, spinal; EPN_YAP, methylation class ependymoma, YAP fusion; ETMR, methylation class embryonal tumor with multilayered rosettes; EWS, methylation class Ewing sarcoma; GBM_G34, methylation class glioblastoma, IDH wildtype, H3.3 G34 mutant; GBM_MES, mesenchymal; GBM_MID, midline; GBM_MYCN, MYCN; GBM_RTK_I, RTK I; GBM_RTK_II, RTK II; GBM_RTK_III, RTK III; HGNET_BCOR, methylation class CNS high grade neuroepithelial tumor with BCOR alteration; HGNET_MN1, methylation class CNS high grade neuroepithelial tumor with MN1 alteration; HMB, methylation class hemangioblastoma; IHG, methylation class infantile hemispheric glioma; LGG_DIG_DIA, methylation class low grade glioma, desmoplastic infantile astrocytoma/ganglioglioma; LGG_DNT, methylation class low grade glioma, dysembryoplastic neuroepithelial tumor; LGG_GG, methylation class low grade glioma, ganglioglioma; LGG_MYB, methylation class low grade glioma, MYB/MYBL1; LGG_PA_GG_ST, methylation class low grade glioma, subclass hemispheric pilocytic astrocytoma and ganglioglioma; LGG_PA_MID, midline pilocytic astrocytoma; LGG_PA_PF, posterior fossa pilocytic astrocytoma; LGG_RGNT, methylation class low grade glioma, rosette forming glioneuronal tumor; LGG_SEGA, methylation class low grade glioma, subependymal giant cell astrocytoma; LIPN, methylation class cerebellar liponeurocytoma; LYMPHO, methylation class lymphoma; MB_G3, group 3; MB_G4, group 4; MB_SHH_CHL_AD, SHH A (children and adult); MB_SHH_INF, SHH B (infant); MB_WNT, WNT; MELAN, methylation class melanoma; MELCYT, methylation class melanocytoma; MNG, methylation class meningioma; O_IDH, 1p/19q codeleted oligodendroglioma; PGG_nC, methylation class paraganglioma, spinal non-CIMP; PIN_T_PB_A, methylation class pineoblastoma group A/intracranial retinoblastoma; PIN_T_PB_B, methylation class pineoblastoma group B; PIN_T_PPT, methylation class pineal parenchymal tumor; PITAD_ACTH, methylation class pituitary adenoma, ACTH; PITAD_FSH_LH, methylation class pituitary adenoma, FSH/LH; PITAD_PRL, methylation class pituitary adenoma, prolactin; PITAD_STH_DNS_A, methylation class pituitary adenoma, STH densely granulated, group A; PITAD_STH_DNS_B, methylation class pituitary adenoma, STH densely granulated, group B; PITAD_STH_SPA, methylation class pituitary adenoma, STH sparsely granulated; PITAD_TSH, methylation class pituitary adenoma, TSH; PITUI, methylation class pituicytoma/granular cell tumor/spindle cell oncocytoma; PLASMA, methylation class plasmacytoma; PLEX_AD, adult; PLEX_PED_A, paediatric A; PLEX_PED_B, paediatric B; PTPR_A, methylation class papillary tumor of the pineal region group A; PTPR_B, methylation class papillary tumor of the pineal region group B; PXA, methylation class (anaplastic) pleomorphic xanthoastrocytoma; RETB, methylation class retinoblastoma; SCHW, methylation class schwannoma; SCHW_MEL, methylation class melanotic schwannoma; SFT_HMPC, methylation class solitary fibrous tumor/hemangiopericytoma; SUBEPN_PF, methylation class subependymoma, posterior fossa; SUBEPN_SPINE, methylation class subependymoma, spinal; SUBEPN_ST, methylation class subependymoma, supratentorial.

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