MASSpy: Building, simulating, and visualizing dynamic biological models in Python using mass action kinetics

Mathematical models of metabolic networks utilize simulation to study system-level mechanisms and functions. Various approaches have been used to model the steady state behavior of metabolic networks using genome-scale reconstructions, but formulating dynamic models from such reconstructions continues to be a key challenge. Here, we present the Mass Action Stoichiometric Simulation Python (MASSpy) package, an open-source computational framework for dynamic modeling of metabolism. MASSpy utilizes mass action kinetics and detailed chemical mechanisms to build dynamic models of complex biological processes. MASSpy adds dynamic modeling tools to the COnstraint-Based Reconstruction and Analysis Python (COBRApy) package to provide an unified framework for constraint-based and kinetic modeling of metabolic networks. MASSpy supports high-performance dynamic simulation through its implementation of libRoadRunner; the Systems Biology Markup Language (SBML) simulation engine. Three case studies demonstrate how to use MASSpy: 1) to simulate dynamics of detailed mechanisms of enzyme regulation; 2) to generate an ensemble of kinetic models using Monte Carlo sampling to approximate missing numerical values of parameters and to quantify uncertainty, and 3) to overcome issues that arise when integrating experimental data with the computation of functional states of detailed biological mechanisms. MASSpy represents a powerful tool to address challenge that arise in dynamic modeling of metabolic networks, both at a small and large scale. Author Summary Genome-scale reconstructions of metabolism appeared shortly after the first genome sequences became available. Constraint-based models are widely used to compute steady state properties of such reconstructions, but the attainment of dynamic models has remained elusive. We thus developed the MASSpy software package, a framework that enables the construction, simulation, and visualization of dynamic metabolic models. MASSpy is based on the mass action kinetics for each elementary step in an enzymatic reaction mechanism. MASSpy seamlessly unites existing software packages within its framework to provide the user with various modeling tools in one package. MASSpy integrates community standards to facilitate the exchange of models, giving modelers the freedom to use the software for different aspects of their own modeling workflows. Furthermore, MASSpy contains methods for generating and simulating ensembles of models, and for explicitly accounting for biological uncertainty. MASSpy has already demonstrated success in a classroom setting. We anticipate that the suite of modeling tools incorporated into MASSpy will enhance the ability of the modeling community to construct and interrogate complex dynamic models of metabolism.