Fig. 3

Validation analysis of inferred PPGL subtype-specific MRs. a Validation analysis for SDH-loss MRs. Mean inferred regulon log₂(fold-change) for discovery SDH-loss transcriptomic signature is shown on the x-axis. The same quantification performed for a SDH-loss transcriptomic signature derived from an independent PPGL cohort is shown on the y-axis. Regulon size (number of genes) is indicated by the relative size of the data points. b Validation analysis for VHL-loss MRs. Analysis method is the same as in panel (a). c Hierarchical clustering of discovery cohort PPGL specimen MR transcription factor activity profiles inferred by the VIPER algorithm. Color bars indicate specimen characteristics and MR type, as shown. d Hierarchical clustering of validation cohort specimen MR transcription factor activity profiles. Color bars indicate specimen characteristics, as shown. e EPAS1 activity for RET, NF1, SDHB, SDHC, SDHD, and VHL specimens in the validation cohort. f EPAS1 activity for discovery cohort normal adrenal medulla specimens and SDHB-null PPGL tumors annotated as “metastatic” or “non-malignant”. g EPAS1 activity of discovery cohort normal adrenal medulla specimens and SDHD-null PPGL tumors of the head and neck and those arising from abdomen and thorax