Efficient parameter estimation for ODE models of cellular processes using semi-quantitative data.

MOTIVATION: Quantitative dynamical models facilitate the understanding of biological processes and the prediction of their dynamics. The parameters of these models are commonly estimated from experimental data. Yet, experimental data generated from different techniques do not provide direct information about the state of the system but a nonlinear (monotonic) transformation of it. For such semi-quantitative data, when this transformation is unknown, it is not apparent how the model simulations and the experimental data can be compared. RESULTS: We propose a versatile spline-based approach for the integration of a broad spectrum of semi-quantitative data into parameter estimation. We derive analytical formulas for the gradients of the hierarchical objective function and show that this substantially increases the estimation efficiency. Subsequently, we demonstrate that the method allows for the reliable discovery of unknown measurement transformations. Furthermore, we show that this approach can significantly improve the parameter inference based on semi-quantitative data in comparison to available methods. AVAILABILITY AND IMPLEMENTATION: Modelers can easily apply our method by using our implementation in the open-source Python Parameter EStimation TOolbox (pyPESTO) available at https://github.com/ICB-DCM/pyPESTO.

pyPESTO: a modular and scalable tool for parameter estimation for dynamic models.

SUMMARY: Mechanistic models are important tools to describe and understand biological processes. However, they typically rely on unknown parameters, the estimation of which can be challenging for large and complex systems. pyPESTO is a modular framework for systematic parameter estimation, with scalable algorithms for optimization and uncertainty quantification. While tailored to ordinary differential equation problems, pyPESTO is broadly applicable to black-box parameter estimation problems. Besides own implementations, it provides a unified interface to various popular simulation and inference methods. AVAILABILITY AND IMPLEMENTATION: pyPESTO is implemented in Python, open-source under a 3-Clause BSD license. Code and documentation are available on GitHub (https://github.com/icb-dcm/pypesto).