ČEŠKA, Milan, David ŠAFRÁNEK, Sven DRAŽAN and Luboš BRIM. Robustness Analysis of Stochastic Biochemical Systems. Plos One. SAN FRANCISCO: PUBLIC LIBRARY SCIENCE, 2014, vol. 9, No 4, p. 1-23. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0094553.
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Basic information
Original name Robustness Analysis of Stochastic Biochemical Systems
Authors ČEŠKA, Milan (203 Czech Republic, belonging to the institution), David ŠAFRÁNEK (203 Czech Republic, belonging to the institution), Sven DRAŽAN (203 Czech Republic, belonging to the institution) and Luboš BRIM (203 Czech Republic, guarantor, belonging to the institution).
Edition Plos One, SAN FRANCISCO, PUBLIC LIBRARY SCIENCE, 2014, 1932-6203.
Other information
Original language English
Type of outcome Article in a journal
Field of Study 10201 Computer sciences, information science, bioinformatics
Country of publisher United States of America
Confidentiality degree is not subject to a state or trade secret
WWW URL
Impact factor Impact factor: 3.234
RIV identification code RIV/00216224:14330/14:00075751
Organization unit Faculty of Informatics
Doi http://dx.doi.org/10.1371/journal.pone.0094553
UT WoS 000335227400014
Keywords in English stochastic models; robustness analysis; probabilistic model checking
Tags International impact, Reviewed
Changed by Changed by: prof. RNDr. Luboš Brim, CSc., učo 197. Changed: 16/4/2019 09:30.
Abstract
We propose a new framework for rigorous robustness analysis of stochastic biochemical systems that is based on probabilistic model checking techniques. We adapt the general definition of robustness introduced by Kitano to the class of stochastic systems modelled as continuous time Markov Chains in order to extensively analyse and compare robustness of biological models with uncertain parameters. The framework utilises novel computational methods that enable to effectively evaluate the robustness of models with respect to quantitative temporal properties and parameters such as reaction rate constants and initial conditions. We have applied the framework to gene regulation as an example of a central biological mechanism where intrinsic and extrinsic stochasticity plays crucial role due to low numbers of DNA and RNA molecules. Using our methods we have obtained a comprehensive and precise analysis of stochastic dynamics under parameter uncertainty. Furthermore, we apply our framework to compare several variants of two-component signalling networks from the perspective of robustness with respect to intrinsic noise caused by low populations of signalling components. We have successfully extended previous studies performed on deterministic models (ODE) and showed that stochasticity may significantly affect obtained predictions. Our case studies demonstrate that the framework can provide deeper insight into the role of key parameters in maintaining the system functionality and thus it significantly contributes to formal methods in computational systems biology.
Links
EE2.3.20.0256, research and development projectName: Vytvoření výzkumného týmu a mezinárodního konzorcia pro počítačový model buňky sinice
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