MR profiles of mouse NEPC are conserved with human NEPC. (A) Strategy. MR analyses: Differential gene expression profiles were converted to protein activity profiles which were then used to identify MRs of NEPC. Analyses were done using species-specific (i.e., mouse or human) regulatory networks as in Vasciaveo et al. (2023). OncoMatch: Individual mouse MR signatures were compared with individual human MR signatures. (B) Heatmap of protein activity-based cluster analysis of non-NEPC and NEPC mouse SB prostate tumors. Projected are the top 15 MRs that distinguish each cluster. Also shown are the activity levels of known MRs of advanced prostate cancer and NEPC. Shown at the top are the phenotype and genotype, quantitative real-time gene expression levels for synaptophysin (Syp) and chromogranin A (ChgA), and enrichment of the Beltran NEPC signature reported in Beltran et al. (2016). (C) OncoMatch heatmap representing conservation of MRs between individual SB tumors (rows, n = 35 samples from 32 independent tumors) and individual patient tumors (columns, n = 49) from the Beltran cohort. Patient features (i.e., assessment of neuroendocrine features and tissue site) are shown on the top horizontal bars, while GEMM features (i.e., phenotype and genotype) are shown on the left side vertical bars. Yellow bars at the top of the heatmaps show the number of GEMMs that match each patient, while the yellow bars on the right side show the number of patients that match each GEMM. The gene set enrichment analysis on the left show representative SB tumor and human patient pairs showing an example of an MR-unmatched (low-fidelity, top) and an MR-matched (high-fidelity, bottom) pair. See also Fig. S2, Table S3, and Table S4.