Decoupled modeling of gene regulatory networks using Michaelis-Menten kinetics

A set of genes and their regulatory interactions are represented in a gene regulatory network (GRN). Since GRNs play a major role in maintaining the cellular activities, inferring these networks is significant for understanding biological processes. Among the models available for GRN reconstruction, our recently developed nonlinear model [1] using Michaelis-Menten kinetics is considered to be more biologically relevant. However, the model remains coupled in the current form making the process computationally expensive, especially for large GRNs. In this paper, we enhance the existing model leading to a decoupled form which not only speeds up the computation, but also makes the model more realistic by representing the strength of each regulatory arc by a distinct Michaelis-Menten constant. The parameter estimation is carried out using differential evolution algorithm. The model is validated by inferring two synthetic networks. Results show that while the accuracy of reconstruction is similar to the coupled model, they are achieved at a faster speed. © Springer International Publishing Switzerland 2015