Ivanic Joseph, Wallqvist Anders, Reifman Jaques
Biotechnology HPC Software Applications Institute, Telemedicine and Advanced Technology Research Center, U,S, Army Medical Research and Materiel Command, Ft, Detrick, MD 21702, USA.
BMC Syst Biol. 2008 Jan 31;2:11. doi: 10.1186/1752-0509-2-11.
Data from high-throughput experiments of protein-protein interactions are commonly used to probe the nature of biological organization and extract functional relationships between sets of proteins. What has not been appreciated is that the underlying mechanisms involved in assembling these networks may exhibit considerable probabilistic behaviour.
We find that the probability of an interaction between two proteins is generally proportional to the numerical product of their individual interacting partners, or degrees. The degree-weighted behaviour is manifested throughout the protein-protein interaction networks studied here, except for the high-degree, or hub, interaction areas. However, we find that the probabilities of interaction between the hubs are still high. Further evidence is provided by path length analyses, which show that these hubs are separated by very few links.
The results suggest that protein-protein interaction networks incorporate probabilistic elements that lead to scale-rich hierarchical architectures. These observations seem to be at odds with a biologically-guided organization. One interpretation of the findings is that we are witnessing the ability of proteins to indiscriminately bind rather than the protein-protein interactions that are actually utilized by the cell in biological processes. Therefore, the topological study of a degree-weighted network requires a more refined methodology to extract biological information about pathways, modules, or other inferred relationships among proteins.
蛋白质 - 蛋白质相互作用的高通量实验数据通常用于探究生物组织的本质，并提取蛋白质组之间的功能关系。尚未得到重视的是，组装这些网络所涉及的潜在机制可能表现出相当大的概率性行为。
我们发现，两种蛋白质之间相互作用的概率通常与其各自相互作用伙伴的数量乘积（即度）成正比。除了高度相互作用区域（即枢纽区域）外，度加权行为在此处研究的整个蛋白质 - 蛋白质相互作用网络中均有体现。然而，我们发现枢纽之间的相互作用概率仍然很高。路径长度分析提供了进一步的证据，表明这些枢纽之间仅由很少的连接分隔。
结果表明，蛋白质 - 蛋白质相互作用网络包含导致丰富尺度层次结构的概率元素。这些观察结果似乎与生物引导的组织方式不一致。对这些发现的一种解释是，我们所看到的是蛋白质无差别结合的能力，而非细胞在生物过程中实际利用的蛋白质 - 蛋白质相互作用。因此，对度加权网络的拓扑研究需要更精细的方法来提取有关蛋白质之间途径、模块或其他推断关系的生物学信息。
