PSAMM: A Portable System for the Analysis of Metabolic Models

The genome-scale models of metabolic networks have been broadly applied in phenotype prediction, evolutionary reconstruction, community functional analysis, and metabolic engineering. Despite the development of tools that support individual steps along the modeling procedure, it is still difficult to associate mathematical simulation results with the annotation and biological interpretation of metabolic models. In order to solve this problem, here we developed a Portable System for the Analysis of Metabolic Models (PSAMM), a new open-source software package that supports the integration of heterogeneous metadata in model annotations and provides a user-friendly interface for the analysis of metabolic models. PSAMM is independent of paid software environments like MATLAB, and all its dependencies are freely available for academic users. Compared to existing tools, PSAMM significantly reduced the running time of constraint-based analysis and enabled flexible settings of simulation parameters using simple one-line commands. The integration of heterogeneous, model-specific annotation information in PSAMM is achieved with a novel format of YAML-based model representation, which has several advantages, such as providing a modular organization of model components and simulation settings, enabling model version tracking, and permitting the integration of multiple simulation problems. PSAMM also includes a number of quality checking procedures to examine stoichiometric balance and to identify blocked reactions. Applying PSAMM to 57 models collected from current literature, we demonstrated how the software can be used for managing and simulating metabolic models. We identified a number of common inconsistencies in existing models and constructed an updated model repository to document the resolution of these inconsistencies.Author Summary: The broad application of genome-scale metabolic modeling has made it a useful technique for tackling fundamental questions in biological research and engineering. Today over 100 models have been constructed for organisms that carry out a diverse array of metabolic activities spanning all three kingdoms of life. These models, however, have been curated independently following different conventions. The maintenance of model consistency has been challenging due to the lack of consensus in model representation and the absence of integrated modeling software for associating mathematical simulations with the annotation and biological interpretation of metabolic models. To solve this problem, we developed a new software package, PSAMM, and a new model format that incorporates heterogeneous, model-specific annotation information into modular representations of model definitions and simulation settings. PSAMM provides significant advances in standardizing the workflow of model annotation and consistency checking. Compared to existing tools, PSAMM supports more flexible configurations and is more efficient in running constraint-based simulations. All functions of PSAMM are freely available for academic users and can be downloaded from a public Git repository (https://zhanglab.github.io/psamm/) under the GNU General Public License.