A robust method for designing multistable systems by embedding bistable subsystems

Wu, Siyuan, Zhou, Tianshou, and Tian, Tianhai (2022) A robust method for designing multistable systems by embedding bistable subsystems. npj Systems Biology and Applications, 8 (10).

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Although multistability is an important dynamic property of a wide range of complex systems, it is still a challenge to develop mathematical models for realising high order multistability using realistic regulatory mechanisms. To address this issue, we propose a robust method to develop multistable mathematical models by embedding bistable models together. Using the GATA1-GATA2-PU.1 module in hematopoiesis as the test system, we first develop a tristable model based on two bistable models without any high cooperative coefficients, and then modify the tristable model based on experimentally determined mechanisms. The modified model successfully realises four stable steady states and accurately reflects a recent experimental observation showing four transcriptional states. In addition, we develop a stochastic model, and stochastic simulations successfully realise the experimental observations in single cells. These results suggest that the proposed method is a general approach to develop mathematical models for realising multistability and heterogeneity in complex systems.

Item ID: 75427
Item Type: Article (Research - C1)
ISSN: 2056-7189
Copyright Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Date Deposited: 17 Jul 2022 23:04
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310299 Bioinformatics and computational biology not elsewhere classified @ 20%
49 MATHEMATICAL SCIENCES > 4901 Applied mathematics > 490102 Biological mathematics @ 80%
SEO Codes: 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280118 Expanding knowledge in the mathematical sciences @ 30%
28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280102 Expanding knowledge in the biological sciences @ 70%
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