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Modelling Epigenetic Information Maintenance: A Kappa Tutorial

机译:建模表观遗传信息维护:kappa教程

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The purpose of this tutorial is to explain and illustrate an approach to the quantitative modelling of molecular interaction networks which departs from the usual notion of (bio-) chemical reaction. This tutorial is self-contained and supposes no familiarity with molecular biology. We shall use a modelling language called Kappa [1], but much of what we will present equally applies to the larger family of rule-based modelling frameworks -and in particular to the BNG language [2] which is very close to Kappa. For a technical exposition of Kappa as a stochastic graph rewriting system, the reader can consult Ref. [3]. To demonstrate the interest of a rule-based approach we will investigate a concrete biological question, that of the maintenance of epigenetic information. Our plan is to: 1. articulate in purely biological terms an epigenetic repair mechanism (§1); 2. capture this mechanism into a simple rule-based model (§2); 3. equip this rule set with numerical information (rule rates, copy numbers of various intervening agents) to obtain a quantitative model (§3.1-3.2); 4. exploit the said model by investigating various questions (§3.3-3.4). Although the model we present here is congruent with the current evidence, and generates interesting results, it offers a -perhaps overly- simplified view of the relevant biological mechanisms. Its primary use is to introduce gradually the Kappa concepts and (some of its) methods in a concrete modelling situation, as we make progress in our plan.
机译:本教程的目的是解释和说明分子相互作用网络的定量建模的方法,这些网络脱离通常概念(生物)化学反应的常规概念。本教程是自我含量的,并且假设没有熟悉分子生物学。我们将使用一个名为Kappa [1]的建模语言,但我们呈现的大部分既往适用于较大的基于规则的建模框架,尤其适用于BNG语言[2],这非常接近Kappa。对于Kappa作为随机图形重写系统的技术展示,读者可以咨询REF。 [3]。为了展示基于规则的方法的兴趣,我们将调查具体的生物问题,即epigenetic信息的维持。我们的计划是:1。在纯粹生物术语中表现出一种表观遗传修复机制(§1); 2.将此机制捕获到基于简单的规则模型(§2); 3.用数值信息(规则速率,各种介入代理的规则数)来装备该规则集以获得定量模型(§3.1-3.2); 4.通过调查各种问题来利用所述模型(§3.3-3.4)。虽然我们在这里呈现的模型是与当前证据一致的,但产生有趣的结果,它提供了对相关生物机制的过度简化的看法。它的主要用途是在具体建模情况下逐步介绍Kappa概念和(其中一些)方法,因为我们在我们的计划中取得进展。

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