FIG. 3: A. The averaged log-likelihood landscape of (a, b) for γ = 10 of the uniform propagator Pn|n0 shows prominent distortions in the contours caused by frequent non-computable transitions. The MLE (cyan) exhibits an obvious bias with respect to the true model parameters (a∗, b∗) (black). B. Inspection of a single time-course (shown on top), evaluated at (a∗, b∗) and at the MLE (bottom), reveals more non-computable transitions (indicated with white boxes below) for the MLE than for the true parameters; however, for those points that can be computed, the MLE probability is higher than for the true parameters, leading to a higher averaged probability and thus to a biased estimate of the parameters (a, b). C. Transition probability in regime I, with (a, b) = (20, 2.5). The transition marked with arrows in (B), from 55 to 57 molecules, results in a negative transition probability. D. The transition matrix for the uniform propagator in regime I from n(t) to n(t+∆t) proteins reveals a large region of non-computable transitions, shown in gray. E. The computability score C(a, b) shows that the MLE is biased towards the region with the lowest computability, for which most transitions are omitted from the averaged log-likelihood score L̄(a, b). F. By contrast, the transition matrix is fully computable in regime II, with (a, b) = (0.5, 100), corresponding to the region of bursty protein synthesis, i.e., to translational bursting.
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