Estimation of Ordinary Differential Equation Models for Gene Regulatory Networks Through Data Cloning.

Ordinary differential equations (ODEs) are widely used for elucidating dynamic processes in various fields. One of the applications of ODEs is to describe dynamics of gene regulatory networks (GRNs), which is a critical step in understanding disease mechanisms. However, estimation of ODE models for GRNs is challenging because of inflexibility of the model and noisy data with complex error structures such as heteroscedasticity, correlations between genes, and time dependency. In addition, either a likelihood or Bayesian approach is commonly used for estimation of ODE models, but both approaches have benefits and drawbacks in their own right. Data cloning is a maximum likelihood (ML) estimation method through the Bayesian framework. Since it works in the Bayesian framework, it is free from local optimum problems that are common drawbacks of ML methods. Also, its inference is invariant for the selection of prior distributions, which is a major issue in Bayesian methods. This study proposes an estimation method of ODE models for GRNs through data cloning. The proposed method is demonstrated through simulation and it is applied to real gene expression time-course data.