Cardiovascular networks: systems-based approaches to cardiovascular disease.
Cardiovascular networks: systems-based approaches to cardiovascular disease.
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DOI：
10.1161/circulationaha.108.847699
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发表时间：
2010-01-05
期刊：
影响因子：
37.8
通讯作者：
Weiss JN
中科院分区：
文献类型：
--
作者：
Lusis AJ;Weiss JN
代谢成各种模块，如图 2A 所示）。 9-11 因此，稀疏链接节点的本地组形成了通过其相应的中心节点链接到其他模块的模块。系统生物学的挑战是为从基因到生物体的每个级别构建详细的生物网络，然后通过整合正交数据集将各个级别连接起来。网络具有几个关键特征，这些特征使它们非常适合响应选择压力而进化的系统，例如通过随机突变和自然选择进行操作的生物系统。对于自组织系统，适应性和鲁棒性等属性与效率一样重要，网络中路径的冗余直观地比纯线性路径更适合适应性和鲁棒性。尽管冗余似乎会损害效率，但网络通过其“小世界”效应克服了这一限制。 12 作为一个例子，考虑一下大肠杆菌使用糖酵解将葡萄糖代谢为丙酮酸以产生 ATP，它突然发现自己暴露于不同的底物，例如丙氨酸（图 2A）。如果大肠杆菌代谢具有线性结构，其中丙氨酸与葡萄糖相去甚远，那么将一系列中间代谢物相互转化以合成葡萄糖以产生 ATP 可能会耗费大量能量（因此生存成本也很高）。然而，在高度互连的网络中，存在将丙氨酸转化为中枢代谢物的酶途径，后者又转化为糖酵解模块中的中枢代谢物（丙酮酸），然后代谢产生 ATP。因此，由于小世界网络中高度互连的中心节点的“短路”效应，大肠杆菌的能量成本被最小化。这类似于机场网络，在机场网络中，飞机在两个小镇之间沿地理上最短路线进行多次停留，可能比从小镇飞往大型枢纽城市（例如芝加哥）然后返回最终目的地所需的时间要长得多，尽管总飞行距离为
of metabolism into various modules as shown in Figure 2A). 9–11 Thus, local groups of sparsely linked nodes form modules that are linked to other modules through their corresponding hub nodes. The challenge of systems biology is to construct detailed biological networks for each level, from the gene to the organism, and then to connect the levels by integrating orthogonal data sets.Networks exhibit several key features that make them well suited for systems evolving in response to selective pressures such as biological systems operating through random mutation and natural selection. For self-organizing systems, properties such as adaptability and robustness are just as important as efficiency, and the redundancy of pathways in a network intuitively lends itself to adaptability and robustness more so than a purely linear pathway. Although redundancy might seem to compromise efficiency, networks overcome this limitation through their “small-world” effects. 12 As an illustration, consider an Escherichia coli using glycolysis to metabolize glucose to pyruvate to generate ATP, which suddenly finds itself exposed to a different substrate such as alanine (Figure 2A). If the E coli metabolism had a linear architecture in which alanine was far removed from glucose, then it could be energetically costly (and hence costly to survival) to interconvert a whole array of intermediate metabolites to synthesize glucose to produce ATP. In a highly interconnected network, however, enzymatic pathways exist to convert the alanine to a hub metabolite, which in turn is converted to the hub metabolite (pyruvate) in the glycolysis module, which is then metabolized to generate ATP. Thus, the energetic cost to the E coli is minimized as a result of the “short-circuiting” effect of the highly interconnected hub nodes in a small-world network. This is analogous to airport networks in which airplanes making many stops to fly the geographically shortest route between 2 small towns may take much longer than flying from the small town to a large hub city (eg, Chicago) and then backtracking to the final destination, even though the total distance traversed is