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GAMES: A dynamic model development workflow for rigorous characterization of synthetic genetic systems

View ORCID ProfileKate E. Dray, View ORCID ProfileJoseph J. Muldoon, View ORCID ProfileNiall M. Mangan, View ORCID ProfileNeda Bagheri, View ORCID ProfileJoshua N. Leonard
doi: https://doi.org/10.1101/2021.10.20.465216
Kate E. Dray
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
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Joseph J. Muldoon
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
2Interdisciplinary Biological Sciences Program, Northwestern University, Evanston, IL 60208, USA
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Niall M. Mangan
3Engineering Sciences and Applied Mathematics Program, Northwestern University, Evanston, IL 60208, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA
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Neda Bagheri
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
2Interdisciplinary Biological Sciences Program, Northwestern University, Evanston, IL 60208, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA
5Departments of Biology and Chemical Engineering, University of Washington, Seattle, WA 98195, USA
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  • For correspondence: j-leonard@northwestern.edu nbagheri@uw.edu
Joshua N. Leonard
1Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL 60208, USA
2Interdisciplinary Biological Sciences Program, Northwestern University, Evanston, IL 60208, USA
4Center for Synthetic Biology, Northwestern University, Evanston, IL 60208, USA
6Chemistry of Life Processes Institute, and Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Evanston, IL 60208, USA
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  • For correspondence: j-leonard@northwestern.edu nbagheri@uw.edu
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Abstract

Mathematical modeling is invaluable for advancing understanding and design of synthetic biological systems. However, the model development process is complicated and often unintuitive, requiring iteration on various computational tasks and comparisons with experimental data. Ad hoc model development can pose a barrier to reproduction and critical analysis of the development process itself, reducing potential impact and inhibiting further model development and collaboration. To help practitioners manage these challenges, we introduce GAMES: a workflow for Generation and Analysis of Models for Exploring Synthetic systems that includes both automated and human-in-the-loop processes. We systematically consider the process of developing dynamic models, including model formulation, parameter estimation, parameter identifiability, experimental design, model reduction, model refinement, and model selection. We demonstrate the workflow with a case study on a chemically responsive transcription factor. The generalizable workflow presented in this tutorial can enable biologists to more readily build and analyze models for various applications.

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Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Manuscript text revised to improve clarity in multiple locations, Figure 4 minor revision, new Supplementary Figure 4 included to provide more detail on potential failure modes, Supplementary Information updated.

  • https://github.com/leonardlab/GAMES

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted December 11, 2021.
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GAMES: A dynamic model development workflow for rigorous characterization of synthetic genetic systems
Kate E. Dray, Joseph J. Muldoon, Niall M. Mangan, Neda Bagheri, Joshua N. Leonard
bioRxiv 2021.10.20.465216; doi: https://doi.org/10.1101/2021.10.20.465216
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GAMES: A dynamic model development workflow for rigorous characterization of synthetic genetic systems
Kate E. Dray, Joseph J. Muldoon, Niall M. Mangan, Neda Bagheri, Joshua N. Leonard
bioRxiv 2021.10.20.465216; doi: https://doi.org/10.1101/2021.10.20.465216

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