Fig. 4. Ligand signalling between tumour and stroma ROIs.

a Overview of ligand to target signalling. Ligands are released from a sender region to activate receptors within a receptor region. These receptors then activate their respective signalling pathways, resulting in the activation of target genes. Therefore, if a ligand is actively signalling to a receiver region, it is expected that there will be a direct correlation between ligand expression in the sender region and target gene expression in the receiver region. The mean Pearson correlation between a ligand and its targets was used to determine a ligands activity between two regions. b Left, Top ligands based on ligand activity signalling from stroma to tumour and stroma to stroma ROIs. Right, circos plot showing ligand signalling from stroma ligands to stroma and tumour targets. The opacity of the arrows indicates the Pearson correlation between ligand and target. c Right, Top ligands signalling from tumour ROIs to stroma or tumour ROIs. Left, Ligand signalling from tumour ligands to tumour and stroma targets. d Gene set enrichment of ligand targets identified in tumour and stroma ROIs. Stroma targeting ligands were enriched for ECM and collagen catabolism associated targets, while tumour targeting ligands were enriched for targets involved in cell survival and inhibition of apoptosis. e Circos plot showing links between cell types present in ROIs and the ligands present in that region. Opacity of the arrows indicates the correlation between ligand and cell type. Only correlations above 0.2 are shown.