(A-2) BioModME for Building and Simulating Dynamic Computational Models of Complex Biological Networks

Introduction:: Introduction: The progress of biological research has mainly relied on experimental investigations but is becoming increasingly coupled to computational modeling. Biological systems and their associated regulation mechanisms and disease processes are intrinsically complex, often encompassing a vast number of interacting components that have become too exhaustive to assess experimentally. Computational modeling, the process of simulating complex systems in silico, has emerged as a powerful tool for generating testable hypotheses by predicting different possible outcomes of biological systems. However, the technical knowledge required to design and solve computational models is a barrier for most experimental and clinical investigators. We have developed BioModME, an R/Shiny web application that simplifies the model building and simulation process, which consists of all the tools a researcher needs to design and explore their biological system of interest.


Materials and Methods:: Materials and Methods: BioModME is designed using the open-source R programming language. The application uses the Shiny and bs4dash packages to build its web framework with commonly used bootstrap widgets. The application utilizes the base R libraries and JavaScript plugins for advanced graphic visualizations to create interactive and high customizable plots (ggplot2, Plotly, Dygraphs). Open-source Fortran code is utilized for the ordinary differential equations (ODEs) solver, allowing the constructed biological model to be solved in a precise and timely manner. Source code, tutorials, documentation, and a link to the software can be found at: https://mcw.marquette.edu/biomedical-engineering/computational-systems-biology-lab/biomodme.php.


Results, Conclusions, and Discussions:: Results, Discussion and Conclusion: BioModME is a model building suite that allows the user to create a reaction network to describe a biological system of interest. The application currently supports the creation of single or multi-region models using a variety of common chemical and physical laws. Users are also able to define and create custom reaction and rate laws (mass action, Michaelis-Menten) if they have the need. We have used the application to replicate a computational model of cell cycle in the mitosis phase consisting of over 50 reactions and 26 ODEs (Fig. 1). The ODEs are autogenerated and solved in the program backend, requiring no deviations from the user. The visualization suite provides the user with multiple options to present the model simulation, including pre-built color palettes, line/axis options, and plotting themes. All model tables, including parameters, equations, initial conditions, and ODEs are exportable in a variety of formats, including a well-structured latex report. Users may also download the underlying code for their model in a “ready to run” scripts in either MATLAB, R, or Python. The application allows for the import and export of SBML file format, a common model storage language used by modeling community, allowing the application to not only be used for building models but also to simulate and modify existing models. BioModME comes with full documentation, featuring derivations for every rate law used in the program, unit conversion for parameters and variables, stepwise tutorials, and full explanations on how to use each component of the application. Lastly, users can perform parameter estimation for unknown model parameters by uploading or creating experimental data to fit the model solution to. Overall, the application consists of all the tools a scientist would need to construct, solve, and explore computational models of biological systems.


Acknowledgements (Optional): :

References (Optional): :