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

被引:28
作者
Bonzanni, Nicola [1 ,2 ]
Krepska, Elzbieta [2 ]
Feenstra, K. Anton [1 ]
Fokkink, Wan [2 ]
Kielmann, Thilo [2 ]
Bal, Henri [2 ]
Heringa, Jaap [1 ]
机构
[1] Vrije Univ Amsterdam, Ctr Integrat Bioinformat, NL-1081 HV Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Dept Comp Sci, NL-1081 HV Amsterdam, Netherlands
关键词
MEDIATED DOWN-REGULATION; CAENORHABDITIS-ELEGANS; PETRI-NET; CELL FATES; PATHWAYS; LIN-12/NOTCH; INDUCTION; RAS; ACTIVATION; SYSTEMS;
D O I
10.1093/bioinformatics/btp355
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:2049 / 2056
页数:8
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