Fig. 3
From: Mitochondrial origins of fractional control in regulated cell death
Decomposing sources of cell-to-cell variability. a Schema for a simple cellular response, y ∈ {0, 1}, to the activation of pathway components w1, w2, x, z, and q representing the natural logarithm of abundances of each biological constituent subject to a dose of stimulus s. b Single-cell data were simulated to demonstrate the feasibility of CCV decomposition by sampling virtual cells (see Supplementary Note 3.3.4 for details). c The dose response of N = 10,000 simulated cells and n = 100 replicate experiments in which kx = 0.25, \(k_{w_1} = 0.5\), kz = 1, kq = 1.5, and \(k_{w_2} = 2\). Error bars represent ± one standard deviation about the mean. The probability density of the components given the cell state being live or dead from a single replicate experiment reveals how the logarithm of abundances of each biological entity correlates with cell state (left column). We further examine the dependence of cell survival on TRAIL by examining the probability of the cell state, y = 1, given the dose, the DEPICTIVE inferred parameters associated with a single replicate simulation, and the abundance of each biological component (right column). Quantitative assessment of the true (black) and the average DEPICTIVE inferred (gray) parameters kx, kz, kq ± one standard deviation (d) and the corresponding variance explained by each component (e). f The scaling of the IC50(i) with i = x, z, or q ± one standard deviation
