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Properties of PPINs: transitivity

Figure 19 Topological clusters reflecting biological function. Clusters are highlighted within dashed-line squares: I – Proteasomal machinery; II – translation-related protein cluster, containing several ribosomal proteins; III – energy production-related cluster, containing several mitochondrial ATPases. Image reproduced with permission of the authors of Hsia et al. Int J Mol Sci. 2015: 16. (7).

Another crucial characteristic of PPINs is their modularity. The transitivity or clustering coefficient of a network is a measure of the tendency of the nodes to cluster together. High transitivity means that the network contains communities or groups of nodes that are densely connected internally. Following an analogy from the social sciences, “the friends of my friends are my friends”. In biological networks, finding these communities is very important, because they can reflect functional modules and protein complexes (Figure 19).

A module is an exchangeable functional unit. They are self-contained components of a system with well-defined interfaces with other components. The defining feature of a module is that its intrinsic functional properties do not change when it is placed in a different context.  Modules help reduce the complexity of biological networks by giving us a set of reducible, functional units that can be studied as an integrated entity. Topological study of PPINs can help detect and define these modules.

Protein complexes can be considered a type of module in which proteins are interacting with each other in a stable manner, maintaining a more or less fixed configuration in time and space. They represent multi-protein machineries with specific functions. A broader type of functional module does not require the proteins to be stably bound to each other as long as its intrinsic functional properties do not change when placed in another context.

The study of modules is also useful when defining intermodular interactions and proteins. These are the edges/nodes that link different communities within a network. They can act as switches or high-level modulators that, for example, mediate cross-talk between different complexes or pathways.

We will talk more in detail about the search for modules in PPINs in a further section. Now let’s talk about the main strategies that can be used to analyse PPINs.