Robustness in gene circuits: clustering of functional responses

In contrast to engineering applications, in which the structure of control laws are designed to satisfy prescribed function requirements, in biology it is often necessary to infer gene-circuit function from incomplete data on gene-circuit structure. By using the feed-forward loop as a model system, this paper introduces a technique for classifying gene-circuit function given gene-circuit structure. In simulations performed on a comprehensive set of models that span a broad range of parameter space, some designs are robust, producing one unique type of functional response regardless of parameter selection. Other designs may exhibit a variety of functional responses, depending upon parameter values. We conclude that, although some feed-forward loop models have designs that lend themselves to unique function inference, others have designs for which the function type may be uncertain.