NIMCE: A Gene Regulatory Network Inference Approach Based on Multi Time Delays Causal Entropy

Gene regulatory networks (GRNs)are involved in various biological processes, such as cell cycle, differentiation and apoptosis. The existing large amount of expression data, especially the time-series expression data, provide a chance to infer GRNs by computational methods. These data can reveal the dynamics of gene expression and imply the regulatory relationships among genes. However, identify the indirect regulatory links is still a big challenge as most studies treat time points as independent observations, while ignoring the influences of time delays. In this study, we propose a GRN inference method based on information-theory measure, called NIMCE. NIMCE incorporates the transfer entropy to measure the regulatory links between each pair of genes, then applies the causation entropy to filter indirect relationships. In addition, NIMCE applies multi time delays to identify indirect regulatory relationships from candidate genes. Experiments on simulated and colorectal cancer data show NIMCE outperforms than other competing methods. All data and codes used in this study are publicly available at https://github.com/CSUBioGroup/NIMCE.