Davila-Velderrain J, Martinez-Garcia J C, Alvarez-Buylla E R
Laboratorio de Genética Molecular, Desarrollo y Evolución de Plantas, Instituto de Ecología, Universidad Nacional Autónoma de México, Ciudad Universitaria, Av. Universidad 3000, México D.F., 04510, Mexico.
Methods Mol Biol. 2015;1284:455-79. doi: 10.1007/978-1-4939-2444-8_23.
Network modeling is now a widespread practice in systems biology, as well as in integrative genomics, and it constitutes a rich and diverse scientific research field. A conceptually clear understanding of the reasoning behind the main existing modeling approaches, and their associated technical terminologies, is required to avoid confusions and accelerate the transition towards an undeniable necessary more quantitative, multidisciplinary approach to biology. Herein, we focus on two main network-based modeling approaches that are commonly used depending on the information available and the intended goals: inference-based methods and system dynamics approaches. As far as data-based network inference methods are concerned, they enable the discovery of potential functional influences among molecular components. On the other hand, experimentally grounded network dynamical models have been shown to be perfectly suited for the mechanistic study of developmental processes. How do these two perspectives relate to each other? In this chapter, we describe and compare both approaches and then apply them to a given specific developmental module. Along with the step-by-step practical implementation of each approach, we also focus on discussing their respective goals, utility, assumptions, and associated limitations. We use the gene regulatory network (GRN) involved in Arabidopsis thaliana Root Stem Cell Niche patterning as our illustrative example. We show that descriptive models based on functional genomics data can provide important background information consistent with experimentally supported functional relationships integrated in mechanistic GRN models. The rationale of analysis and modeling can be applied to any other well-characterized functional developmental module in multicellular organisms, like plants and animals.
网络建模如今在系统生物学以及整合基因组学中已成为一种广泛应用的方法,它构成了一个丰富多样的科学研究领域。为了避免混淆并加速向生物学中一种不可否认的、必要的、更具定量性和多学科性的方法转变,需要对主要现有建模方法背后的推理及其相关技术术语有概念清晰的理解。在此,我们重点关注两种主要的基于网络的建模方法,它们通常根据可用信息和预期目标来使用:基于推理的方法和系统动力学方法。就基于数据的网络推理方法而言,它们能够发现分子成分之间潜在的功能影响。另一方面,基于实验的网络动力学模型已被证明非常适合对发育过程进行机制性研究。这两种观点是如何相互关联的呢?在本章中,我们描述并比较这两种方法,然后将它们应用于一个特定的发育模块。在逐步实际实施每种方法的过程中,我们还着重讨论它们各自的目标、效用、假设以及相关局限性。我们以拟南芥根干细胞龛模式形成中涉及的基因调控网络(GRN)作为示例。我们表明,基于功能基因组学数据的描述性模型可以提供与整合在机制性GRN模型中的实验支持的功能关系相一致的重要背景信息。分析和建模的基本原理可应用于多细胞生物中任何其他特征明确的功能性发育模块,如植物和动物。