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Bioinformatics Advance Access originally published online on June 10, 2009
Bioinformatics 2009 25(16):2049-2056; doi:10.1093/bioinformatics/btp355
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Executing multicellular differentiation: quantitative predictive modelling of C.elegans vulval development

Nicola Bonzanni 1,2, Elzbieta Krepska 2, K. Anton Feenstra 1,*, Wan Fokkink 2, Thilo Kielmann 2, Henri Bal 2 and Jaap Heringa 1

1Centre for Integrative Bioinformatics and 2Department of Computer Science, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands

*To whom correspondence should be addressed.


  Abstract

Motivation: Understanding the processes involved in multi-cellular pattern formation is a central problem of developmental biology, hopefully leading to many new insights, e.g. in the treatment of various diseases. Defining suitable computational techniques for development modelling, able to perform in silico simulation experiments, is an open and challenging problem.

Results: Previously, we proposed a coarse-grained, quantitative approach based on the basic Petri net formalism, to mimic the behaviour of the biological processes during multicellular differentiation. Here, we apply our modelling approach to the well-studied process of Caenorhabditis elegans vulval development. We show that our model correctly reproduces a large set of in vivo experiments with statistical accuracy. It also generates gene expression time series in accordance with recent biological evidence. Finally, we modelled the role of microRNA mir-61 during vulval development and predict its contribution in stabilizing cell pattern formation.

Contact: feenstra{at}few.vu.nl

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Olga Troyanskaya

Received on October 22, 2008; revised on May 25, 2009; accepted on June 4, 2009

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