Stochasticity is necessary for multiple attractors in a class of differentiation networks
Deterministic models remain the most common option for modeling gene regulatory networks even when the underlying assumptions of high copy numbers and fast promoter kinetics are unsatisfied. Here, we analyze a widely studied differentiation network motif known as the PU.1-GATA-1 circuit and we show...
| Main Authors: | , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Institute of Electrical and Electronics Engineers (IEEE)
2019
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| Online Access: | https://hdl.handle.net/1721.1/121528 |
| _version_ | 1826200161770012672 |
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| author | Kumar, Nithin Senthur Al-Radhawi, Muhammad Ali Sontag, Eduardo D. Del Vecchio, Domitilla |
| author2 | Massachusetts Institute of Technology. Department of Mechanical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Mechanical Engineering Kumar, Nithin Senthur Al-Radhawi, Muhammad Ali Sontag, Eduardo D. Del Vecchio, Domitilla |
| author_sort | Kumar, Nithin Senthur |
| collection | MIT |
| description | Deterministic models remain the most common option for modeling gene regulatory networks even when
the underlying assumptions of high copy numbers and fast promoter kinetics are unsatisfied. Here, we analyze a widely studied differentiation network motif known as the PU.1-GATA-1 circuit and we show that an ODE model of the biomolecular reactions consistent with known biology is incapable of exhibiting multistability, a defining behaviour for such a network. Thus, we consider the chemical master equation model of the same biomolecular reactions and using results recently developed by the authors, we analytically construct the stationary distribution. We show that this distribution is indeed capable of admitting a multitude of modes. We illustrate the results with a numerical example. |
| first_indexed | 2024-09-23T11:32:07Z |
| format | Article |
| id | mit-1721.1/121528 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:32:07Z |
| publishDate | 2019 |
| publisher | Institute of Electrical and Electronics Engineers (IEEE) |
| record_format | dspace |
| spelling | mit-1721.1/1215282022-09-27T20:11:09Z Stochasticity is necessary for multiple attractors in a class of differentiation networks Kumar, Nithin Senthur Al-Radhawi, Muhammad Ali Sontag, Eduardo D. Del Vecchio, Domitilla Massachusetts Institute of Technology. Department of Mechanical Engineering Ali Al-Radhawi, Muhammad Deterministic models remain the most common option for modeling gene regulatory networks even when the underlying assumptions of high copy numbers and fast promoter kinetics are unsatisfied. Here, we analyze a widely studied differentiation network motif known as the PU.1-GATA-1 circuit and we show that an ODE model of the biomolecular reactions consistent with known biology is incapable of exhibiting multistability, a defining behaviour for such a network. Thus, we consider the chemical master equation model of the same biomolecular reactions and using results recently developed by the authors, we analytically construct the stationary distribution. We show that this distribution is indeed capable of admitting a multitude of modes. We illustrate the results with a numerical example. United States. Air Force. Office of Scientific Research (Grant FA9550-14-1-0060) 2019-07-09T12:10:52Z 2019-07-09T12:10:52Z 2018-06 Article http://purl.org/eprint/type/ConferencePaper 1095-323X https://hdl.handle.net/1721.1/121528 Kumar, Nithin S., M. Ali Al-Radhawi, Eduardo D. Sontag and Domitilla Del Vecchio. "Stochasticity is necessary for multiple attractors in a class of differentiation networks." In Proceeding 2018 IEEE Conference Decision and Control, pages 1886-1892. en_US https://ieeexplore.ieee.org/xpl/mostRecentIssue.jsp?punumber=8410068 Proceeding 2018 IEEE Conference Decision and Control Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Institute of Electrical and Electronics Engineers (IEEE) Ali Al-Radhawi, Muhammad |
| spellingShingle | Kumar, Nithin Senthur Al-Radhawi, Muhammad Ali Sontag, Eduardo D. Del Vecchio, Domitilla Stochasticity is necessary for multiple attractors in a class of differentiation networks |
| title | Stochasticity is necessary for multiple attractors in a class of differentiation networks |
| title_full | Stochasticity is necessary for multiple attractors in a class of differentiation networks |
| title_fullStr | Stochasticity is necessary for multiple attractors in a class of differentiation networks |
| title_full_unstemmed | Stochasticity is necessary for multiple attractors in a class of differentiation networks |
| title_short | Stochasticity is necessary for multiple attractors in a class of differentiation networks |
| title_sort | stochasticity is necessary for multiple attractors in a class of differentiation networks |
| url | https://hdl.handle.net/1721.1/121528 |
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