Inference of gene regulatory networks with multi-objective cellular genetic algorithm

Abstract

Reverse engineering of biochemical networks remains an important open challenge in computational systems biology. The goal of model inference is to, based on time-series gene expression data, obtain the sparse topological structure and parameters that quantitatively understand and reproduce the dynamics of biological systems. In this paper, we propose a multi-objective approach for the inference of S-System structures for Gene Regulatory Networks (GRNs) based on Pareto dominance and Pareto optimality theoretical concepts instead of the conventional single-objective evaluation of Mean Squared Error (MSE). Our motivation is that, using a multi-objective formulation for the GRN, it is possible to optimize the sparse topology of a given GRN as well as the kinetic order and rate constant parameters in a decoupled S-System, yet avoiding the use of additional penalty weights. A flexible and robust Multi-Objective Cellular Evolutionary Algorithm is adapted to perform the tasks of parameter learning and network topology inference for the proposed approach. The resulting software, called MONET, is evaluated on real-based academic and synthetic time-series of gene expression taken from the DREAM3 challenge and the IRMA in vivo datasets. The ability to reproduce biological behavior and robustness to noise is assessed and compared. The results obtained are competitive and indicate that the proposed approach offers advantages over previously used methods. In addition, MONET is able to provide experts with a set of trade-off solutions involving GRNs with different typologies and MSEs.

Keywords: Cellular genetic algorithms; DREAM challenge; Gene regulatory networks; Multi-objective optimization.