Faculty of Management, Wrocław University of Science and Technology, Wrocław, Poland.
Department of Life Sciences and Chemistry, Jacobs University, 28759, Bremen, Germany.
Sci Rep. 2022 Nov 19;12(1):19906. doi: 10.1038/s41598-022-23775-9.
In a highly simplified view, a disease can be seen as the phenotype emerging from the interplay of genetic predisposition and fluctuating environmental stimuli. We formalize this situation in a minimal model, where a network (representing cellular regulation) serves as an interface between an input layer (representing environment) and an output layer (representing functional phenotype). Genetic predisposition for a disease is represented as a loss of function of some network nodes. Reduced, but non-zero, output indicates disease. The simplicity of this genetic disease model and its deep relationship to percolation theory allows us to understand the interplay between disease, network topology and the location and clusters of affected network nodes. We find that our model generates two different characteristics of diseases, which can be interpreted as chronic and acute diseases. In its stylized form, our model provides a new view on the relationship between genetic mutations and the type and severity of a disease.
从高度简化的角度来看，可以将疾病视为遗传易感性和不断变化的环境刺激相互作用下出现的表型。我们在一个最小模型中形式化了这种情况，其中网络（代表细胞调节）作为输入层（代表环境）和输出层（代表功能表型）之间的接口。疾病的遗传易感性表现为一些网络节点的功能丧失。输出减少但非零，表示患病。这种遗传疾病模型的简单性及其与渗流理论的深刻关系使我们能够理解疾病、网络拓扑以及受影响网络节点的位置和簇之间的相互作用。我们发现，我们的模型产生了两种不同的疾病特征，可以解释为慢性和急性疾病。在其风格化的形式中，我们的模型提供了一种新的视角，来看待基因突变与疾病的类型和严重程度之间的关系。
