On the Concepts of Modularity and Retroactivity in Systems Biology
Modularity and retroactivity are two highly recurrent concepts in the recent research in systems biology. There could be many interpretations for these two concepts. As Sauro says in his recent paper in Nature Molecular Systems Biology a bioinformatician with an eye on graph theory will view modules as loosely linked islands of densely connected nodes, on the other hand a geneticist might see modules as groups of coexpressed genes. In engineering, instead, a module is defined as a functional unit that is capable of maintaining its intrinsic properties irrespective of what it is connected to.
In order to describe retroactivity, wew can imagine that a cell contains a network that behaves as an oscillator and the oscillator in turns used to signal another process. Such an example might include the P35/Mdm2 oscillator that signals DNA repair (Tyson, 2006). Now we can consider the process by which the oscillator transmits its signal; it must and can only transmit this signal through a physical connection. Therefore, the downstream process must bind to proteins generated within the oscillator in order to ‘perceive’ the signal. However, in the process of binding proteins from the oscillator, there is the potential to disrupt the functioning of the oscillator since part of the oscillator is effectively being sequestered. The effect a downstream process has on an upstream process is called retroactivity and is at the heart of defining what is and what isn’t a module.
Moreover we can say that the less the retroactivity (a smaller R), the more the confidence we have in making the assertion that the upstream and downstream. Operationally, retroactivity measures the relative difference between the dynamics of two systems, one intact and another disconnected at the designated node. The modular structure of the entire network can be determined from the pattern of retroactivity. Moreover, modules defined in this manner have a very useful operational meaning; they can in principle be excised from the network and reinserted elsewhere with the prediction that they will operate as expected.
One might ask how important is this kind of modularity to biology? From an evolutionary perspective there is a growing awareness that modularity may facilitate evolutionary change by encouraging the ability to rewire modules while maintaining modular function (McAdams et al, 2004; Kirschner and Gerhart, 2005). This concept has been termed facilitated variation.
From: (Sauro, MSB 2008)