Complexity and modularity of intracellular networks: a systematic approach for modelling and simulation

IET Systems Biology
Michael BlinovIon I Moraru

Abstract

Assembly of quantitative models of large complex networks brings about several challenges. One of them is the combinatorial complexity, where relatively few signalling molecules can combine to form thousands or millions of distinct chemical species. A receptor that has several separate phosphorylation sites can exist in hundreds of different states, many of which must be accounted for individually when simulating the time course of signalling. When assembly of protein complexes is being included, the number of distinct molecular species can easily increase by a few orders of magnitude. Validation, visualisation and understanding the network can become intractable. Another challenge appears when the modeller needs to recast or grow a model. Keeping track of changes and adding new elements present a significant difficulty. An approach to solve these challenges within the virtual cell (VCell) is described. Using (i) automatic extraction from pathway databases of model components (http://vcell.org/biopax) and (ii) rules of interactions that serve as reaction network generators (http://vcell.org/bionetgen), a way is provided for semi-automatic generation of quantitative mathematical models that also facilitates the reuse of model el...Continue Reading

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Citations

Aug 24, 2010·Theory in Biosciences = Theorie in Den Biowissenschaften·Oliver Ruebenacker, Michael Blinov
Jun 10, 2009·Tissue Engineering. Part B, Reviews·Amanda W LundGeorge E Plopper
Jul 16, 2010·Journal of Biomedical Semantics·Allyson L ListerAnil Wipat
Oct 20, 2009·Journal of Biology·Bruce J MayerLeslie M Loew
Oct 30, 2010·IET Systems Biology·Oliver RuebenackerMichael Blinov
Aug 16, 2014·BMC Systems Biology·Brenden K PetersenC Anthony Hunt
Nov 22, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tim F E PaffenE W Meijer

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