Fig. 4: OSDR infers a pulse-generating excitable circuit of T and B cells in the breast cancer microenvironment.

a, Ki67 marker as a function of neighbourhood composition. Each point corresponds to one T cell (73,961 cells) from the IMC dataset of Danenberg et al.². b, Same as a but for B cells (27,642 cells). c, OSDR inferred phase portrait indicates an excitable system. The blue highlighted trajectory displays a large pulse of adaptive immune cells. d, Spatial simulation of a 2 mm × 2 mm tissue based on inferred population dynamics shows that a high enough number of T cells triggers a pulse of T cells followed by B cells. The y axis displays the number of cells, normalized to the area of a 80-µm neighbourhood. e, Each pulse is followed by a refractory period, as evidenced in simulations in which additional T cells are introduced at different times (vertical arrows). A new pulse is generated only when T cells are introduced after B cells from the previous pulse have declined. f, 3D phase portrait with CD4 T cells, CD8 T cells and B cells shows an immune flare when the CD4 T cell density crosses threshold. The 2D projections are in grey. g, Distributions of CD4 T cells, CD8 T cells and B cells in the 100 most-proliferative and least-proliferative states of each cell type. The most-proliferative states are characterized by a high density of CD4 T cells and a low density of B cells.