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A MATLAB Toolbox for Modeling Genetic Circuits in Cell-Free Systems

Singhal, Vipul and Tuza, Zoltan A. and Sun, Zachary Z. and Murray, Richard M. (2020) A MATLAB Toolbox for Modeling Genetic Circuits in Cell-Free Systems. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20200806-153554109

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Abstract

We introduce a MATLAB based simulation toolbox, called txtlsim, for an E. coli based Transcription-Translation (TX- TL) system. This toolbox accounts for several cell-free related phenomena, such as resource loading, consumption, and degradation, and in doing so, models the dynamics of TX-TL reactions for the entire duration of batch-mode experiments. We use a Bayesian parameter inference approach to characterize the reaction rate parameters associated with the core transcription, translation and mRNA degradation mechanics of the toolbox, allowing it to reproduce constitutive mRNA and protien expression trajectories. We demonstrate the use of this characterized toolbox in a circuit behavior prediction case study for an incoherent feed-forward loop.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.08.05.237990DOIDiscussion Paper
https://github.com/vipulsinghal02/txtlsim_buildacellRelated ItemData/Code
ORCID:
AuthorORCID
Singhal, Vipul0000-0003-1670-1824
Tuza, Zoltan A.0000-0003-2896-1527
Sun, Zachary Z.0000-0002-9425-2924
Murray, Richard M.0000-0002-5785-7481
Additional Information: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 4.0 International license. Posted August 05, 2020. We thank Kyle Martin, Shaobin Guo and Clarmyra Hayes for laboratory assistance, and Vincent Noireaux and Michael Jewett for advice on extract preparation methods. We thank Anandh Swaminathan, William Poole, and Samuel Clamons for useful discussions about the computational methodology. This material is based upon work supported in part by the Defense Advanced Research Projects Agency (DARPA/MTO) Living Foundries program, contract number HR0011-12-C- 0065 (DARPA/CMO); the Air Force Office of Scientific Research, grant number FA9550-14-1-0060; and DARPA SBIR contract W911NF-16-P-0003 (Caltech subcontract from Synvitrobio, Inc.). VS was supported by the National Science Scholarship (NSS-PhD), Agency for Science, Technology, and Research (A*STAR), Singapore. ZAT was supported by the Fulbright Scholarship. ZZS was supported by a UCLA/Caltech Medical Scientist Training Program fellowship, and a National Defense Science and Engineering Graduate fellowship. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing officially policies, either expressly or implied, of the Defense Advanced Research Projects Agency or the U.S. Government. Competing Interest Statement: RMM and ZZS declare a conflict of interest: RMM, ZZS hold ownership in Tierra Biosciences (formerly Synvitrobio). The work presented here was funded off of a DARPA SBIR to Synvitrobio, Inc. (ZZS), contract No: W911NF-16-P-0003, and a Caltech Grubstake Grant (RMM, ZZS). Author's Contributions: RMM conceived of the txtlsim toolbox, and VS, ZAT and RMM wrote it. ZZS conceived of the experiments and collected the data, and VS conceived of and performed the parameter inference strategy. VS wrote the manuscript. All authors edited it.
Funders:
Funding AgencyGrant Number
Defense Advanced Research Projects Agency (DARPA)HR0011-12-C-0065
Air Force Office of Scientific Research (AFOSR)FA9550-14-1-0060
Defense Advanced Research Projects Agency (DARPA)W911NF-16-P-0003
Agency for Science, Technology and Research (A*STAR)UNSPECIFIED
Fulbright FoundationUNSPECIFIED
UCLA-Caltech Medical Scientist Training ProgramUNSPECIFIED
National Defense Science and Engineering Graduate (NDSEG) FellowshipUNSPECIFIED
Subject Keywords:Cell-Free Synthetic Biology, Genetic Circuits, Mathematical Modeling, Chemical Reaction Networks, Parameter Inference
Record Number:CaltechAUTHORS:20200806-153554109
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200806-153554109
Official Citation:A MATLAB Toolbox for Modeling Genetic Circuits in Cell-Free Systems. Vipul Singhal, Zoltan A. Tuza, Zachary Sun, Richard M Murray. bioRxiv 2020.08.05.237990; doi: https://doi.org/10.1101/2020.08.05.237990
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104782
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Aug 2020 22:57
Last Modified:06 Aug 2020 22:57

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