Large scale modeling of genetic networks using gene knockout data

Gene regulatory network (GRN) represents a set of genes and their regulatory interactions. The inference of the regulatory interactions between genes is usually carried out as an optimization problem using an appropriate mathematical model and the time-series gene expression data. Among the various models proposed for GRN inference, our recently proposed Michaelis-Menten kinetics based ODE model provides a good trade-off between the computational complexity and biological relevance. This model, like other known GRN models, also uses an evolutionary algorithm for parameter estimation. Since the search space for large networks is huge, leading to a low accuracy of inference, it is important to reduce the search region for improved performance of the optimization algorithm. In this paper, we propose a classification method using gene knockout data to eliminate a large infeasible region from the optimization search area. We also propose a method for partial inference of regulations when all the regulators of a given regulated gene are unregulated genes. The proposed method is evaluated by reconstructing in silico networks of large sizes.