Executing multicellular differentiation: quantitative predictive modelling of C. elegans vulval development
Executing multicellular differentiation: quantitative predictive modelling of C. elegans vulval development
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DOI：
10.1093/bioinformatics/btp355
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发表时间：
2009-08-15
期刊：
影响因子：
5.8
通讯作者：
Heringa, Jaap
中科院分区：
文献类型：
--
作者：
Bonzanni, Nicola;Krepska, Elzbieta;Heringa, Jaap
动机：了解多细胞模式形成的过程是发育生物学的一个中心问题，有望带来许多新的见解，如：G.治疗各种疾病。定义合适的计算技术的发展建模，能够在硅片模拟experiments，是一个开放的和具有挑战性的problem.Results：以前，我们提出了一个粗粒度的，定量的方法的基础上的基本Petri网形式主义，模仿行为的生物过程中多细胞分化。在这里，我们将我们的建模方法应用到秀丽隐杆线虫外阴发育的研究过程中。我们表明，我们的模型正确地再现了大量的体内实验的统计精度。它还根据最近的生物学证据生成基因表达时间序列。最后，我们模拟了microRNA mir-61在外阴发育过程中的作用，并预测了其在稳定细胞模式形成中的作用。
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.