A modular systems biological modelling framework studies cyclic nucleotide signaling in platelets
Breitenbach T, Englert N, Osmanoglu O, Rukoyatkina N, Wangorsch G, Heinze K, Friebe A, Butt E, Feil R, Dittrich M, Gambaryan S, Dandekar T (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 550
Article Number: 111222
DOI: 10.1016/j.jtbi.2022.111222
Abstract
Background: The cyclic nucleotides cAMP and cGMP inhibit platelet activation. Different platelet signaling modules work together. We develop here a modelling framework to integrate different signaling modules and apply it to platelets. Results: We introduce a novel standardized bilinear coupling mechanism allowing sub model debugging and standardization of coupling with optimal data driven modelling by methods from optimization. Besides cAMP signaling our model considers specific cGMP effects including external stimuli by drugs. Moreover, the output of the cGMP module serves as input for a modular model of VASP phosphorylation and for the activity of cAMP and cGMP pathways in platelets. Experimental data driven modeling allows us to design models with quantitative output. We use the condensed information about involved regulation and system responses for modeling drug effects and obtaining optimal experimental settings. Stepwise further validation of our model is given by direct experimental data. Conclusions: We present a general framework for model integration using modules and their stimulus responses. We demonstrate it by a multi-modular model for platelet signaling focusing on cGMP and VASP phosphorylation. Moreover, this allows to estimate drug action on any of the inhibitory cyclic nucleotide pathways (cGMP, cAMP) and is supported by experimental data.
Involved external institutions
Julius-Maximilians-Universität Würzburg
Germany (DE)
Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS)
Russian Federation (RU)
Eberhard Karls Universität Tübingen
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Germany (DE)
Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS)
Russian Federation (RU)
Eberhard Karls Universität Tübingen
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
How to cite
APA:
Breitenbach, T., Englert, N., Osmanoglu, O., Rukoyatkina, N., Wangorsch, G., Heinze, K.,... Dandekar, T. (2022). A modular systems biological modelling framework studies cyclic nucleotide signaling in platelets. Journal of Theoretical Biology, 550. https://dx.doi.org/10.1016/j.jtbi.2022.111222
MLA:
Breitenbach, Tim, et al. "A modular systems biological modelling framework studies cyclic nucleotide signaling in platelets." Journal of Theoretical Biology 550 (2022).
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