Wednesday, July 22, 2009

Automatic analysis and construction of feed-forward regulatory networks

Given the assumption that transcriptional regulation is sigmoid shaped, i.e. the steady state diagram of the inducer vs. the target protein has a sigmoid shape (or inverted in the case of a repressor), it might be possible to automatically determine the steady state diagram of a regulatory network with no feedback controls. It might also be possible to generate a feed forward network for a given steady state diagram.

Lets take a simple case, where a transcription factor "a" indirectly upregulates and downregulates the target gene "X", as shown below. Then there are two regulation curves associated with "a". If we assume that a repressor will dominate over an activator, then we can determine what the the final steady state diagram of "X" will be as a function of "a" by looking at the dissociation constants (the center of the sigmoid curves).

The same method can be used to construct networks that have more complex steady state behaviors. For example, suppose "a" and "b" regulate "X" such that the activity of "X" is described by the yellow regions (1,2,3) in the diagram below. Then, it is possible to identify the network that will satisfy each piece and then put the pieces together. The shape of the sigmoid is determined by the dissociation constants.