Abstract
Most transcriptomic studies of SARS-CoV-2 infection have focused on differentially expressed genes, which do not necessarily reveal the genes mediating the transcriptomic changes. In contrast, exploiting curated biological network, our PathExt tool identifies central genes from the differentially active paths mediating global transcriptomic response. Here we apply PathExt to multiple cell line infection models of SARS-CoV-2 and other viruses, as well as to COVID-19 patient-derived PBMCs. The central genes mediating SARS-CoV-2 response in cell lines were uniquely enriched for ATP metabolic process, G1/S transition, leukocyte activation and migration. In contrast, PBMC response reveals dysregulated cell-cycle processes. In PBMC, the most frequently central genes are associated with COVID-19 severity. Importantly, relative to differential genes, PathExt-identified genes show greater concordance with several benchmark anti-COVID-19 target gene sets. We propose six novel anti-SARS-CoV-2 targets ADCY2, ADSL, OCRL, TIAM1, PBK, and BUB1, and potential drugs targeting these genes, such as Bemcentinib, Phthalocyanine, and Conivaptan.
Keywords: DEGs (Differentially Expressed Genes); PBMCs (Peripheral Blood Mononuclear Cells); SARS-C0V-2; cell lines; network analysis; transcriptome.
【저자키워드】 network analysis, Transcriptome., DEGs (Differentially Expressed Genes), PBMCs (Peripheral Blood Mononuclear Cells), SARS-C0V-2, cell lines, 【초록키워드】 COVID-19, viruses, Transcriptome, SARS-CoV-2, SARS-COV-2 infection, severity, Infection, COVID-19 severity, anti-SARS-CoV-2, Peripheral blood, Migration, Concordance, Peripheral blood mononuclear cells, biological network, network analysis, PBMC, target, ATP, Differentially expressed genes, PBMCs, cell lines, target gene, bemcentinib, leukocyte, changes, conivaptan, leukocyte activation, phthalocyanine, DEGs, cell line, G1/S transition, MOST, Genes, transcriptomic, peripheral, Cell, ADCY2, ADSL, BUB1, central genes, e genes, OCRL, TIAM1, greater, identify, reveal, dysregulated, drugs targeting, central gene, curated, metabolic process, PBK, with COVID-19, 【제목키워드】 COVID-19, SARS-CoV-2, drug, target, novel, LINE, Potential, Against,