ORBi: Schliemann Monica - Robustness-based model validation of an apoptosis signalling network model

Reference : Robustness-based model validation of an apoptosis signalling network model


	Document type :	Scientific congresses and symposiums : Paper published in a book
	Discipline(s) :	Engineering, computing & technology : Multidisciplinary, general & others
	To cite this reference:	http://hdl.handle.net/2268/128812

Title :	Robustness-based model validation of an apoptosis signalling network model
Language :	English
Author, co-author :	Schliemann, Monica [Université de Liège - ULg > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation : Méth. computat. pour la bio.syst. >]
	Findeisen, Rolf []
	Bullinger, Eric [Université de Liège - ULg > Dép. d'électric., électron. et informat. (Inst.Montefiore) > Systèmes et modélisation : Méth. computat. pour la bio.syst. >]
Publication date :	2012
Main document title :	Proceedings of the 16th IFAC Symposium on System Identification, Brussels, Belgium, 11–13 July 2012
Pages :	930–935
On invitation :	No
Audience :	International
Event name :	16th IFAC Symposium on System Identification
Event date :	from 11-07-2012 to 13-07-2012
Event place (city) :	Brussels
Event country :	Belgium
Keywords :	[en] polynomial models ; robustness ; perturbation analysis ; biochemical systems
Abstract :	[en] Models of intracellular biochemical reaction networks are difficult to parameterise due to the low number of quantitative time series experimental values. Therefore, model validation or invalidation plays an important role, as it allows to check qualitatively whether a model structure is suited or not to reproduce qualitatively the experimental findings. This paper analyses the robustness of an experimentally validated polynomial differential equation model of TNF-induced pro-and anti-apoptotic signalling. The bistability of the median model is shown robust to large single parameter variations. Only two parameters (XIAP and Procaspase-3 production rates) are shown to be fragile, in particular when changed simultaneously. Therefore, the model seems valid from the point of view of robustness analysis of the bistability. Many biological experiments quantify average concentrations or the percentage of viable cells, while other methods such as microscopy-based experiments observe single cells. The integration of single cell and cell population behaviour of TNF-induced pro- and anti-apoptotic signalling has been achieved via a cell ensemble model, whose robustness is also analysed here. We show that within the cell population there are cells with not only quantitative differences, but also qualitative ones. In particular, all cells are not bistable. The degree of robustness applicable for the median cell is expanded to combine mono- and bistable models. This measure, applied solely to the two-dimensional subspace of fragile parameters, is shown to correlate well with the time of death. While robustness of bistability can serve for model validation of the median cell model, it cannot for the model of the cell population.
Research units :	Giga-Systems Biology and Chemical Biology
Target :	Researchers ; Students
Permalink :	http://hdl.handle.net/2268/128812
DOI :	10.3182/20120711-3-BE-2027.00352

File(s) associated to this reference

Fulltext file(s):

	File	Commentary	Version	Size	Access
Restricted access	Schliemann_2012_SYSID.pdf		Publisher postprint	1.25 MB	Request copy

All documents in ORBi are protected by a user license.

Dspace v1.5