Gene Biomarker Prediction in Glioma by Integrating scRNA-seq Data and the Gene Regulatory Network

Abstract

Background: Although great efforts have been made to study the occurrence and development of glioma, the molecular mechanisms of glioma are still unclear. Single-cell sequencing technology provides a new perspective for researchers to explore the pathogens of tumors to further help make treatment and prognosis decisions for patients with tumors.Methods: In this study, we proposed an algorithm framework to explore the molecular mechanisms of glioma by integrating single-cell gene expression profiles and gene regulatory relations. First, since there were great differences among malignant cells from different glioma samples, we analyzed the expression status of malignant cells for each sample, and then tumor consensus genes were identified by constructing and analyzing cell-specific networks. Second, to comprehensively analyze the characteristics of glioma, we integrated transcriptional regulatory relationships and consensus genes to construct a tumor-specific regulatory network. Third, we performed a hybrid clustering analysis to identify glioma cell types. Finally, candidate tumor marker genes were identified based on cell types and known glioma-related genes.Results: We got six identified cell types using the method we proposed and for these cell types, we performed functional and biological pathway enrichment analyses. The candidate tumor marker genes were analyzed through survival analysis and verified using literature from PubMed.Conclusions: The results showed that these candidate tumor marker genes were closely related to glioma and could provide clues for the diagnosis and prognosis of patients with glioma. In addition, we found that four of the candidate tumor marker genes (NDUFS5, NDUFA1, NDUFA13, and NDUFB8) belong to the NADH ubiquinone oxidoreductase subunit gene family, so we inferred that this gene family may be strongly related to glioma.