A Consensus Gene Regulatory Network for Neurodegenerative Diseases Using Single-Cell RNA-Seq Data.

Gene regulatory network (GRN) inference from gene expression data is a highly complex and challenging task in systems biology. Despite the challenges, GRNs have emerged, and for complex diseases such as neurodegenerative diseases, they have the potential to provide vital information and identify key regulators. However, every GRN method produced predicts results based on its assumptions, providing limited biological insights. For that reason, the current work focused on the development of an ensemble method from individual GRN methods to address this issue. Four state-of-the-art GRN algorithms were selected to form a consensus GRN from their common gene interactions. Each algorithm uses a different construction method, and for a more robust behavior, both static and dynamic methods were selected as well. The algorithms were applied to a scRNA-seq dataset from the CK-p25 mus musculus model during neurodegeneration. The top subnetworks were constructed from the consensus network, and potential key regulators were identified. The results also demonstrated the overlap between the algorithms for the current dataset and the necessity for an ensemble approach. This work aims to demonstrate the creation of an ensemble network and provide insights into whether a combination of different GRN methods can produce valuable results.