Fig. 4: ContactTracing identifies ER stress as a central mediator of CIN-induced immune suppression.

a, ContactTracing Circos plot highlighting all CIN- and STING-dependent interactions. Each segment represents a cell type, and cell types are further divided into ligands and receptors, which are ordered according to the first diffusion component (DC1) computed on differentially expressed genes (DEGs) in each cell type conditioned on ligand/receptor expression. Outer rings encode CIN-dependent interactions, which include target (receptor-expressing) cells distinguished by ≥10 CIN-dependent interaction effects (two-sided P value, FDR Q value < 0.25), as well as CIN-dependent ligands complementing those receptors (FDR Q value < 0.05 and abs(log₂(ligand expression FC) > 0.12)). The outer circle represents cell type. The next circle shows the DC1 score for ligand/receptor represented at that coordinate; for example, macrophage response states were organized from pro-inflammatory to anti-inflammatory polarization states. The next circle shows the correlation between the log-normalized expression of that ligand/receptor and its CIN-dependent differential abundance (log₂(FC) as computed by Milo in local neighbourhoods and mapped to single cells as the described in the Methods). The histogram in the next inner circle shows the number of significant CIN-dependent interaction effects (FDR Q value < 0.25). Ribbons in the middle link interacting [ligand, donor cell type] and [receptor, target cell type] pairs; ribbon thickness is proportional to the number of genes exhibiting a CIN- and STING-dependent interaction effect (whichever is greater) and colour represents CIN- and STING-dependent log₂(FC) of its complementary ligand measured in the donor cell type (whichever is greater). Links are only shown if they exhibit (1) CIN- and STING-dependent expression of ligand in donor cells (in the same direction with FDR Q value < 0.05 and abs(log₂(expression FC) > 0.12)) and (2) at least 10 CIN-dependent and 10 STING-dependent interaction effects in the target cell type. Ligands/receptors are labelled at ribbon ends; ligands are in black and receptors in grey. The data encoded in the ContactTracing Circos plot are provided in Supplementary Table 9 and may be explored interactively at http://contacttracing.laughneylab.com/circos. b, Differentially expressed pathways associated with CIN- and STING-dependent, tumour-derived ligands that effect the TME with nominal P < 0.05. The y axis is scaled by −log₁₀(P values) times the sign of the odds ratio and colour indicates the pathway odds ratio. c, Bar plot highlighting CIN- and STING-dependent tumour-derived ligands that affect the TME, as described in a. d, Schematic illustrating the impact of chronic STING activation on functions associated with ligand effects.