GRNMOPT: Inference of gene regulatory networks based on a multi-objective optimization approach

Background and objective: The reconstruction of gene regulatory networks (GRNs) stands as a vital approach in deciphering complex biological processes. The application of nonlinear ordinary differential equations (ODEs) models has demonstrated considerable efficacy in predicting GRNs. Notably, the decay rate and time delay are pivotal in authentic gene regulation, yet their systematic determination in ODEs models remains underexplored. The development of a comprehensive optimization framework for the effective estimation of these key parameters is essential for accurate GRN inference. Method: This study introduces GRNMOPT, an innovative methodology for inferring GRNs from time-series and steady-state data. GRNMOPT employs a combined use of decay rate and time delay in constructing ODEs models to authentically represent gene regulatory processes. It incorporates a multi-objective optimization approach, optimizing decay rate and time delay concurrently to derive Pareto optimal sets for these factors, thereby maximizing accuracy metrics such as AUROC (Area Under the Receiver Operating Characteristic curve) and AUPR (Area Under the Precision-Recall curve). Additionally, the use of XGBoost for calculating feature importance aids in identifying potential regulatory gene links. Results: Comprehensive experimental evaluations on two simulated datasets from DREAM4 and three real gene expression datasets (Yeast, In vivo Reverse-engineering and Modeling Assessment [IRMA], and Escherichia coli [E. coli]) reveal that GRNMOPT performs commendably across varying network scales. Furthermore, cross- validation experiments substantiate the robustness of GRNMOPT. Conclusion: We propose a novel approach called GRNMOPT to infer GRNs based on a multi-objective optimization framework, which effectively improves inference accuracy and provides a powerful tool for GRNs inference.