A review on gene regulatory network reconstruction algorithms based on single cell RNA sequencing

Abstract

BackgroundUnderstanding gene regulatory networks (GRNs) is essential for unraveling the molecular mechanisms governing cellular behavior. With the advent of high-throughput transcriptome measurement technology, researchers have aimed to reverse engineer the biological systems, extracting gene regulatory rules from their outputs, which represented by gene expression data. Bulk RNA sequencing, a widely used method for measuring gene expression, has been employed for GRN reconstruction. However, it falls short in capturing dynamic changes in gene expression at the level of individual cells since it averages gene expression across mixed cell populations.ObjectiveIn this review, we provide an overview of 15 GRN reconstruction tools and discuss their respective strengths and limitations, particularly in the context of single cell RNA sequencing (scRNA-seq).MethodsRecent advancements in scRNA-seq break new ground of GRN reconstruction. They offer snapshots of the individual cell transcriptomes and capturing dynamic changes. We emphasize how these technological breakthroughs have enhanced GRN reconstruction.ConclusionGRN reconstructors can be classified based on their requirement for cellular trajectory, which represents a dynamical cellular process including differentiation, aging, or disease progression. Benchmarking studies support the superiority of GRN reconstructors that do not require trajectory analysis in identifying regulator-target relationships. However, methods equipped with trajectory analysis demonstrate better performance in identifying key regulatory factors. In conclusion, researchers should select a suitable GRN reconstructor based on their specific research objectives.