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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. [ABSTRACT FROM PUBLISHER]