A gene regulatory network (GRN) represents a collection of genes, connected via regulatory interactions. Reverse engineering GRNs is a challenging problem in systems biology. Various models have been proposed for modeling GRNs. However, many of these models lack the capability to explain the molecular mechanisms underlying the biological process. Michaelis-Menten kinetics can be used to model the biomolecular mechanisms and is a widely used non-linear approach to represent biochemical systems. However, the model in its current form is not suitable for reverse engineering biological systems. In this paper, based on Michaelis-Menten kinetics, we develop a new model to reverse engineer GRNs. The parameter estimation is formulated as an optimization problem which is solved by adapting trigonometric differential evolution (TDE), a variant of differential evolution (DE). The model is applied for reconstructing both in silico and in vivo networks. The results are promising and as the model is fully biologically relevant, it provides a new perspective for accurate GRN inference.
A gene regulatory network (GRN) represents a set of genes and its regulatory interactions. The inference of the regulatory interactions between genes is usually carried out using an appropriate mathematical model and the available gene expression profile. Among the various models proposed for GRN inference, our recently proposed Michaelis–Menten 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. Considering various issues associated with such population based stochastic optimization approaches (e.g. diversity, premature convergence due to local optima, accuracy, etc.), it becomes important to seed the initial population with good individuals which are closer to the optimal solution. In this paper, we exploit the inherent strength of principal component analysis (PCA) in a novel manner to initialize the population for GRN optimization. The benefit of the proposed method is validated by reconstructing in silico and in vivo networks of various sizes. For the same level of accuracy, the approach with PCA based initialization shows improved convergence speed.