Analyzing pharmacological intervention points: A method to calculate external stimuli to switch between steady states in regulatory networks
Please always quote using this URN: urn:nbn:de:bvb:20-opus-220385
- Once biological systems are modeled by regulatory networks, the next step is to include external stimuli, which model the experimental possibilities to affect the activity level of certain network’s nodes, in a mathematical framework. Then, this framework can be interpreted as a mathematical optimal control framework such that optimization algorithms can be used to determine external stimuli which cause a desired switch from an initial state of the network to another final state. These external stimuli are the intervention points for theOnce biological systems are modeled by regulatory networks, the next step is to include external stimuli, which model the experimental possibilities to affect the activity level of certain network’s nodes, in a mathematical framework. Then, this framework can be interpreted as a mathematical optimal control framework such that optimization algorithms can be used to determine external stimuli which cause a desired switch from an initial state of the network to another final state. These external stimuli are the intervention points for the corresponding biological experiment to obtain the desired outcome of the considered experiment. In this work, the model of regulatory networks is extended to controlled regulatory networks. For this purpose, external stimuli are considered which can affect the activity of the network’s nodes by activation or inhibition. A method is presented how to calculate a selection of external stimuli which causes a switch between two different steady states of a regulatory network. A software solution based on Jimena and Mathworks Matlab is provided. Furthermore, numerical examples are presented to demonstrate application and scope of the software on networks of 4 nodes, 11 nodes and 36 nodes. Moreover, we analyze the aggregation of platelets and the behavior of a basic T-helper cell protein-protein interaction network and its maturation towards Th0, Th1, Th2, Th17 and Treg cells in accordance with experimental data.…
Author: | Tim Breitenbach, Chunguang Liang, Niklas Beyersdorf, Thomas Dandekar |
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URN: | urn:nbn:de:bvb:20-opus-220385 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Institut für Virologie und Immunbiologie |
Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften | |
Language: | English |
Parent Title (English): | PLoS Computational Biology |
Year of Completion: | 2019 |
Volume: | 15 |
Article Number: | e1007075 |
Source: | PLoS Computational Biology (2019) 15:e1007075. https://doi.org/10.1371/journal.pcbi.1007075 |
DOI: | https://doi.org/10.1371/journal.pcbi.1007075 |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
Release Date: | 2024/09/19 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |