Mathematical modeling of the full dose-response curve yielded a higher estimated EC50 (180-525 nm) compared to the classical interpretation (46-191 nm) by accounting for non-steady-state conditions.
Does mathematical modeling improve EC50 estimations from classical dose-response curves in chicken heart tissue?
Mathematical modeling allows for re-interpretation of dose-response datasets to provide more accurate EC50 estimates when steady-state measurements are not feasible.
UNLABELLED: The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. DATABASE: The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman.
Nyman et al. (Tue,) reported a other. Mathematical modeling approach vs. Classical interpretation was evaluated on EC50 estimation. Mathematical modeling of the full dose-response curve yielded a higher estimated EC50 (180-525 nm) compared to the classical interpretation (46-191 nm) by accounting for non-steady-state conditions.