Martens, Harald, Veflingstad, Siren R., Plahte, Erik, Martens, M. (Magni), Bertrand, Dominique and Omholt, Stig W.. (2009) The genotype-phenotype relationship in multicellular pattern-generating models - the neglected role of pattern descriptors. BMC Systems Biology, Vol.3 (Articl). ISSN 1752-0509

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Abstract

Background: A deep understanding of what causes the phenotypic variation arising from biological patterning processes, cannot be claimed before we are able to recreate this variation by mathematical models capable of generating genotype-phenotype maps in a causally cohesive way. However, the concept of pattern in a multicellular context implies that what matters is not the state of every single cell, but certain emergent qualities of the total cell aggregate. Thus, in order to set up a genotype-phenotype map in such a spatiotemporal pattern setting one is actually forced to establish new pattern descriptors and derive their relations to parameters of the original model. A pattern descriptor is a variable that describes and quantifies a certain qualitative feature of the pattern, for example the degree to which certain macroscopic structures are present. There is today no general procedure for how to relate a set of patterns and their characteristic features to the functional relationships, parameter values and initial values of an original pattern-generating model. Here we present a new, generic approach for explorative analysis of complex patterning models which focuses on the essential pattern features and their relations to the model parameters. The approach is illustrated on an existing model for Delta-Notch lateral inhibition over a two-dimensional lattice. Results: By combining computer simulations according to a succession of statistical experimental designs, computer graphics, automatic image analysis, human sensory descriptive analysis and multivariate data modelling, we derive a pattern descriptor model of those macroscopic, emergent aspects of the patterns that we consider of interest. The pattern descriptor model relates the values of the new, dedicated pattern descriptors to the parameter values of the original model, for example by predicting the parameter values leading to particular patterns, and provides insights that would have been hard to obtain by traditional methods. Conclusion: The results suggest that our approach may qualify as a general procedure for how to discover and relate relevant features and characteristics of emergent patterns to the functional relationships, parameter values and initial values of an underlying pattern-generating mathematical model.

Item Type:	Journal Article
Subjects:	Q Science > QH Natural history > QH426 Genetics
Divisions:	Faculty of Science > Centre for Systems Biology
Library of Congress Subject Headings (LCSH):	Phenotype -- Research, Pattern formation (Biology) -- Research, Gene mapping -- Mathematical models, Lattice theory
Journal or Publication Title:	BMC Systems Biology
Publisher:	BioMed Central Ltd.
ISSN:	1752-0509
Date:	4 September 2009
Volume:	Vol.3
Number:	Articl
Identification Number:	10.1186/1752-0509-3-87
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	National Programme for Research in Functional Genomics in Norway (FUGE), Norges forskningsråd [Norwegian Research Council]
Grant number:	151924/S10 (FUGE)
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URI:	http://wrap.warwick.ac.uk/id/eprint/2169

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