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).

Efficient computation of adjoint sensitivities at steady-state in ODE models of biochemical reaction networks.

Dynamical models in the form of systems of ordinary differential equations have become a standard tool in systems biology. Many parameters of such models are usually unknown and have to be inferred from experimental data. Gradient-based optimization has proven to be effective for parameter estimation. However, computing gradients becomes increasingly costly for larger models, which are required for capturing the complex interactions of multiple biochemical pathways. Adjoint sensitivity analysis has been pivotal for working with such large models, but methods tailored for steady-state data are currently not available. We propose a new adjoint method for computing gradients, which is applicable if the experimental data include steady-state measurements. The method is based on a reformulation of the backward integration problem to a system of linear algebraic equations. The evaluation of the proposed method using real-world problems shows a speedup of total simulation time by a factor of up to 4.4. Our results demonstrate that the proposed approach can achieve a substantial improvement in computation time, in particular for large-scale models, where computational efficiency is critical.

PEtab-Interoperable specification of parameter estimation problems in systems biology.

Reproducibility and reusability of the results of data-based modeling studies are essential. Yet, there has been-so far-no broadly supported format for the specification of parameter estimation problems in systems biology. Here, we introduce PEtab, a format which facilitates the specification of parameter estimation problems using Systems Biology Markup Language (SBML) models and a set of tab-separated value files describing the observation model and experimental data as well as parameters to be estimated. We already implemented PEtab support into eight well-established model simulation and parameter estimation toolboxes with hundreds of users in total. We provide a Python library for validation and modification of a PEtab problem and currently 20 example parameter estimation problems based on recent studies.