Reconstruction of gene regulatory networks for Caenorhabditis elegans using tree-shaped gene expression data.

Abstract

Constructing gene regulatory networks is a widely adopted approach for investigating gene regulation, offering diverse applications in biology and medicine. A great deal of research focuses on using time series data or single-cell RNA-sequencing data to infer gene regulatory networks. However, such gene expression data lack either cellular or temporal information. Fortunately, the advent of time-lapse confocal laser microscopy enables biologists to obtain tree-shaped gene expression data of Caenorhabditis elegans, achieving both cellular and temporal resolution. Although such tree-shaped data provide abundant knowledge, they pose challenges like non-pairwise time series, laying the inaccuracy of downstream analysis. To address this issue, a comprehensive framework for data integration and a novel Bayesian approach based on Boolean network with time delay are proposed. The pre-screening process and Markov Chain Monte Carlo algorithm are applied to obtain the parameter estimates. Simulation studies show that our method outperforms existing Boolean network inference algorithms. Leveraging the proposed approach, gene regulatory networks for five subtrees are reconstructed based on the real tree-shaped datatsets of Caenorhabditis elegans, where some gene regulatory relationships confirmed in previous genetic studies are recovered. Also, heterogeneity of regulatory relationships in different cell lineage subtrees is detected. Furthermore, the exploration of potential gene regulatory relationships that bear importance in human diseases is undertaken. All source code is available at the GitHub repository https://github.com/edawu11/BBTD.git.