Fig. 7: NB metastasis to the BM is featured by a functional and dynamic gene set having potential clinical interest.

a Dot plot showing the level of expression of NB gene signatures built from the avian model (avian-PT, avian-BM) and from patient data (patient-PT and patient-BM) in NB cells located in primary tumors or in the bone marrow in each context (avian model and patients) (two-sided Wilcoxon rank sum test; p-value < 0.05, log fold change > 0.1, min.pct > 0.1). b Decision tree to extract a list of candidate genes functionally involved in BM invasion by NB cells. c Upset plot of the 164 genes enriched during BM invasion in the embryonic model of NB dissemination (and expressed in patient samples) in the 7 patient BM compared to paired PT. Yellow bars indicate pools of genes which expression profile is shared by at least 5 out of the 7 patients. Bar plot of the fraction of genes from signature conserved in each patient is shown on the right. d Heatmap of the expression of BM invasion signature refined from patient samples data (65 genes) in paired PT/BM patient samples and in NB cells at each step of dissemination. e Distribution of effect scores of the 65 BM-genes calculated using Chronos algorithms on CRISPR/Cas9 data from DepMap portal on 18 NB cell lines obtained from metastatic sites. Graphs are shown for the 25 genes associated with significant NB dependency for cell growth as detailed in the methods section. Data are normalized using annotated sets of common-essential and non-essential genes. No effect on cell growth has a score of 0, and a negative score is indicative of gene dependency for cell growth. f Heatmap of gene expression ratios (BM over PT) of the 25 genes extracted in (e). Values of BM/PT ratio for each gene and for each patient are indicated on the heatmap. g Scheme summarizing the types of dynamic transcriptomic adaptations occurring in NB cells across disease progression in an entire growing organism. Source data are provided as a source data file.