August 22, 2008

A relatively recent read of Yu and Gerstein’s 2006 PNAS paper has got me thinking about analogies and metaphors in biological networks. As Yu points out, protein-protein interaction networks have frequently been compared to social communication networks … sharing characteristics such as small-world and scale-free properties. Yu presents a plausible analogy between transcriptional regulatory networks and organizational control structures (in other words, a form of bureaucracy). The difference, as Yu states is, “more oriented towards control than communication.”

I’ve been reading and thinking quite a bit lately about biological networks with respect to genetic interactions such as synthetic lethal (& synthetic sick), rescue, and dosage compensation. Oversimplifying, in all these cases the network is able to adjust to perturbation … sometimes in, as of yet, unpredictable fashion. The buzz words here are redundancy and robustness. A decent analogy already exist in this arena. Primarily associated with metabolic networks, the pipe analogy represents the pathways through the network as pipes which flow metabolites to reach some final destination. So a perturbation is effectively a disruption to a pipe. For robustness you depend on some other pipe in the system to pick up the load.

But lately I’ve been thinking of a different analogy. In this analogy the network is like a sports team. Pick your favorite sport as an example and follow along, but for now I’ll use (indoor) volleyball. Members of the team specialize in playing their particular position: a setter, a blocker, a libero (defense specialist), and hitters (attackers). You put six players on the court at any time, but have a bench full of alternative players. Traditionally your bench players are also somewhat specialized in their preferred roles but aren’t as good as your starters. Some of these alternate players are utilized for particular circumstances which arise frequently during the course of a game. Any and all players may be asked, in the course of a game, to perform duties outside their specialty, but rarely is a game decided by these plays.

So I hope you see the analogy. The players are components of the network and the function of the network is to win. Every component has a specialized function but is also likely capable of doing other functions (pleiotropy). Bench players are a form of redundancy but also specialization. You pick the components because they do particular jobs well and combinations of components because together they get the job done (winning). The ball, as it were, is now the information or stimulus which sets the whole gang into motion.

Let me stretch the analogy a bit further …. mutations (changes) come in two forms: players who improve (new workout or nutritional habits — rare) and those that get hurt (their game is “off”). But lets say, for the moment, that our star setter gets hurt so badly that she can’t even play (a deletion). Without the setter, the team can’t hold it together (she’s essential) and lose. Or, perhaps, the rest of the team may be able to compensate for her loss and still win (she was not essential) using different complements of players or slightly different strategies. These wins may be less convincing (reduced fitness), the team may present particular inadequacies which make it susceptible to specific attacks (environmental effects), or it may be very sensitive to the damage or loss of other players (synthetic lethals). Sometimes, rarely, the team discovers that it is actually better without the injured player (increased fitness).

Good sports teams are definitely organic in their abilities and play, but perhaps this analogy is too much of a stretch. Maybe it’s not that good of an analogy to begin with, and perhaps it isn’t “useful”. But it is at least timely, because of the current Olympics games.

Yu H. and Gerstein M. (2006). Genomic analysis of the hierarchical structure of regulatory networks. PNAS 103(40), 14724-14731. DOI: 10.1073/pnas.0508637103


2 Responses to “Analogy”

  1. I like the analogy in particular because it separates the well the phenotype that is under selection pressure (to win) from the detailed implementation (the team). It would be good introduction material in a talk 🙂

  2. Peter Says:

    Great example of analogy! I really like it!
    Recently I started posting interestnig analogies I found on the web on I thought it could be a good idea to create a place where people can share useful analogies. Check it out!

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