Integrative Analysis of DNA Methylation and Gene Expression Data Identifies Potential Biomarkers and Functional Epigenetic Modules for SARS-CoV-2

To integrate gene expression and DNA methylation data and find the potential role of DNA methylation in the invasion and replication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We first conducted differential expression and methylation analysis between the coronavirus disease of 2019 (COVID-19) and healthy controls. FEM was employed to identify functional epigenetic modules, from which a diagnostic model for COVID-19 was built. SKA1 and WSB1 modules were identified, with SKA1 module enriched in COVID-19 replication and transcription, and WSB1 module related to ubiquitin-protein activity. The differentially expressed or differentially methylated genes in these two modules could be used to distinguish COVID-19 from healthy controls, with AUC reaching 1 and 0.98 for SKA1 and WSB1 modules, respectively. Two epigenetically activated genes (CENPM and KNL1) from the SKA1 module were upregulated in HPV- or HBV-positive tumor samples and were found to be significantly associated with the survival of tumor patients. In conclusion, the identified FEM modules and potential signatures play an essential role in the replication and transcription of coronavirus.