论文标题

基因调节网络的渗透

Percolation on the gene regulatory network

论文作者

Torrisi, Giuseppe, Kühn, Reimer, Annibale, Alessia

论文摘要

我们考虑了基因调节的简化模型,其中基因表达受转录因子(TF)的调节,后者是单蛋白或蛋白质复合物。蛋白质反过来又是从表达的基因合成的,从而产生了调节的反馈回路。这导致了一个定向的二分网络,如果基因编码促进TF的蛋白质,则存在从基因到TF的链接,并且如果TF调节基因的表达,则存在从TF到基因的链接。基因和TF均被建模为二进制变量,分别表明基因是否表达,并且TF合成。我们考虑了要合成TF的情况,必须表达其所有贡献基因。这导致了TFS动力学的``'和'门逻辑。通过将渗透理论调整为定向的两分图,根据逻辑动力学演变,我们能够确定在网络参数空间中,在稳定的细胞类型中,在噪声下,双方网络可以支持双方稳定基因表达模式,在嘈杂的条件下,根据稳定的稳定条件。 特别是,该分析揭示了双稳定性区域的可能性,在该区域中,广泛的渗透簇是或对扰动没有弹性的可能性。这与标准渗滤理论中观察到的过渡大不相同。最后,我们考虑涉及模仿基因敲除实验的单节点去除的扰动。结果揭示了基因基因敲除级联对基础网络动力学实现的逻辑的强烈依赖性,特别是强调了雪崩大小与基因 - 基因相互作用网络不易相关。

We consider a simplified model for gene regulation, where gene expression is regulated by transcription factors (TFs), which are single proteins or protein complexes. Proteins are in turn synthesised from expressed genes, creating a feedback loop of regulation. This leads to a directed bipartite network in which a link from a gene to a TF exists if the gene codes for a protein contributing to the TF, and a link from a TF to a gene exists if the TF regulates the expression of the gene. Both genes and TFs are modelled as binary variables, which indicate, respectively, whether a gene is expressed or not, and a TF is synthesised or not. We consider the scenario where for a TF to be synthesised, all of its contributing genes must be expressed. This results in an ``AND'' gate logic for the dynamics of TFs. By adapting percolation theory to directed bipartite graphs, evolving according to the AND logic dynamics, we are able to determine the necessary conditions, in the network parameter space, under which bipartite networks can support a multiplicity of stable gene expression patterns, under noisy conditions, as required in stable cell types. In particular, the analysis reveals the possibility of a bi-stability region, where the extensive percolating cluster is or is not resilient to perturbations. This is remarkably different from the transition observed in standard percolation theory. Finally, we consider perturbations involving single node removal that mimic gene knockout experiments. Results reveal the strong dependence of the gene knockout cascade on the logic implemented in the underlying network dynamics, highlighting in particular that avalanche sizes cannot be easily related to gene-gene interaction networks.

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