Identification of genetic network dynamics with unate structure

Motivation: Modern experimental techniques for time-course measurement of gene expression enable the identification of dynamical models of genetic regulatory networks. In general, identification involves fitting appropriate network structures and parameters to the data. For a given set of genes, exploring all possible network structures is clearly prohibitive. Modelling and identification methods for the a priori selection of network structures compatible with biological knowledge and experimental data are necessary to make the identification problem tractable. Results: We propose a differential equation modelling framework where the regulatory interactions among genes are expressed in terms of unate functions, a class of gene activation rules commonly encountered in Boolean network modelling. We establish analytical properties of the models in the class and exploit them to devise a two-step procedure for gene network reconstruction from product concentration and synthesis rate time series. The first step isolates a family of model structures compatible with the data from a set of most relevant biological hypotheses. The second step explores this family and returns a pool of best fitting models along with estimates of their parameters. The method is tested on a simulated network and compared to state-of-the-art network inference methods on the benchmark synthetic network IRMA. Contact