Objective
Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells.
Methods
We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML.
Results
Our analysis revealed several challenges to representing WC models using the current standards.
Conclusion
We, therefore, propose several new WC modeling standards, software, and databases.
Significance
We anticipate that these new standards and software will enable more comprehensive models.
The considerable difficulty encountered in reproducing the results of published dynamical models limits validation, exploration and reuse of this increasingly large biomedical research resource. To address this problem, we have developed Tellurium Notebook, a software system for model authoring, simulation, and teaching that facilitates building reproducible dynamical models and reusing models by 1) providing a notebook environment which allows models, Python code, and narrative to be intermixed, 2) supporting the COMBINE archive format during model development for capturing model information in an exchangeable format and 3) enabling users to easily simulate and edit public COMBINE-compliant models from public repositories to facilitate studying model dynamics, variants and test cases. Tellurium Notebook, a Python–based Jupyter–like environment, is designed to seamlessly inter-operate with these community standards by automating conversion between COMBINE standards formulations and corresponding in–line, human–readable representations. Thus, Tellurium brings to systems biology the strategy used by other literate notebook systems such as Mathematica. These capabilities allow users to edit every aspect of the standards–compliant models and simulations, run the simulations in–line, and re–export to standard formats. We provide several use cases illustrating the advantages of our approach and how it allows development and reuse of models without requiring technical knowledge of standards. Adoption of Tellurium should accelerate model development, reproducibility and reuse.
Objective
Reproducibility is the cornerstone of the scientific method. However,
currently, many systems biology models cannot easily be reproduced. This
paper presents methods that address this problem.
Methods
We analyzed the recent Mycoplasma genitalium
whole-cell (WC) model to determine the requirements for reproducible
modeling.
Results
We determined that reproducible modeling requires both repeatable
model building and repeatable simulation.
Conclusion
New standards and simulation software tools are needed to enhance and
verify the reproducibility of modeling. New standards are needed to
explicitly document every data source and assumption, and new deterministic
parallel simulation tools are needed to quickly simulate large, complex
models.
Significance
We anticipate that these new standards and software will enable
researchers to reproducibly build and simulate more complex models,
including WC models.
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