Fig. 6: Intra-tumoral meta-programs underlying NED.

A Heatmap showing scores of 12861 epithelial cells (column, from 6 CRPC patients) for each of 60 programs (rows) derived from NMF analysis of individual samples. Cells and programs are hierarchically clustered, and 3 NE-related meta-programs (P1, P2, and P4) and a cell cycle-related meta-program (P3) are highlighted. B Enrichment scores of prostate lineages: basal, luminal, NE marker genes and AR, stemness, EMT, and cell cycle pathway genes in cells ordered as in (A), with the color-coding for the corresponding CRPC sample. C Pearson correlation between the expression of genes of P1, P2, and P4 and the NE score, as measured by the average expression of 14 known NE markers. Three previously published bulk RNA-seq datasets were used in this analysis, as described in the “Methods” section. Highlighted in red are some known NED genes (Source data are provided as Supplementary Data 1). D Heatmap depicting strong expression of 121 genes (Pearson R ≥ 0.3, as measured by Pearson correlation analysis shown in (C) in AR⁻NE⁺ group of Morrissey dataset. Total samples are divided into five groups as previously suggested in ref. ⁴⁰.