Thursday, August 23, 2007

A modern classic text   posted by p-ter @ 8/23/2007 08:16:00 PM

I recently finished Uri Alon's An Introduction to Systems Biology: Design Principles of Biological Circuits, which I concluded about halfway through was one of the greatest textbooks I've ever read. No joke. It's simply excellent. If you're a biologist with any interest in gene regulation, read this book. If you're a physicist or engineer with any interest in biology, read this book. If your eyes don't glaze over when you read my more technical posts, read this book. Here are a few reasons:

1. The organization of the book itself, and the narration within, is spectacular. Alon takes a classic reductionist look at biological networks-- the whole can be understood by considering the parts. Though the parts, in this case, are not individual genes themselves, but the recurring types of regulatory interactions-- "motifs"-- that are seen in different types of network, biological or otherwise. As he points out multiple times, it didn't have to be this way-- in principle, evolution could have stumbled on incredibly complex network architectures, but that isn't the case. A simple mathematical analysis of two or three node circuits reveals subtle behaviors that are seen over and over again-- it's truly sublime.

2. This is not a laundry list of experiments, tools, and results. Each example is fully explored, both using mathematical models and, where available, experimental results. This leads to a nice fully picture of a mathematical model and its application. And note the math itself is completely accessible to anyone with some exposure to calculus and differential equations.

3. Alon doesn't stop at describing biological networks and their architecture, though he could have stopped there and had an excellent text (the retrospectively obvious points he makes about the different time scales of reaction times in different networks, and the impact that has on network organization, was worth the price of the book alone). He goes on to ask the evolutionary questions: why are certain genes regulated by activators, and others by repressors? In what situations is a certain type of network motif favored, and in which situations is it disfavored or neutral? He closes the book with a quote from Michael Savagaeu that very much resonated with me:
Differences in biochemical details might be the result of historical accidents that are functionally neutral, or they might be governed by additional rules that have yet to be determined. One can always assume that certain differences are the result of historical accident, but such an explanation has no predictive power and tends to stifle the search for alternative hypotheses. It generally tends to be more productive if one starts with the working hypothesis that there are rules. One may end up attributing differences to historical accident, but in my opinion it is a mistake to start there.
Again, read this book.