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Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective.

ABSTRACT: The current pandemic of 2019 novel coronavirus disease (COVID-19) caused by a novel virus strain, 2019-nCoV/SARS-CoV-2 have posed a serious threat to global public health and economy. It is largely unknown how the human immune system responds to this infection. A better understanding of the immune response to SARS-CoV-2 will be important to develop therapeutics against COVID-19. Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and employed a network biology approach to generate human-virus interactome. Network topological analysis discovers 15 SARS-CoV-2 targets, which belongs to a subset of interferon (IFN) stimulated genes (ISGs). These ISGs (IFIT1, IFITM1, IRF7, ISG15, MX1, and OAS2) can be considered as potential candidates for drug targets in the treatments of COVID-19. We have identified significant interaction between ISGs and TLR3 agonists, like poly I: C, and imiquimod, and suggests that TLR3 agonists can be considered as a potential drug for drug repurposing in COVID-19. Our network centric analysis suggests that moderating the innate immune response is a valuable approach to target COVID-19.

SUBMITTER: Prasad K

PROVIDER: S-EPMC7319641 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective.

Prasad Kartikay K Khatoon Fatima F Rashid Summya S Ali Nemat N AlAsmari Abdullah F AF Ahmed Mohammad Z MZ Alqahtani Ali S AS Alqahtani Mohammed S MS Kumar Vijay V

International journal of biological macromolecules 20200626

The current pandemic of 2019 novel coronavirus disease (COVID-19) caused by a novel virus strain, 2019-nCoV/SARS-CoV-2 have posed a serious threat to global public health and economy. It is largely unknown how the human immune system responds to this infection. A better understanding of the immune response to SARS-CoV-2 will be important to develop therapeutics against COVID-19. Here, we have used transcriptomic profile of human alveolar adenocarcinoma cells (A549) infected with SARS-CoV-2 and e ...[more]

PMID: 32599245

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Project description:The aim of the present study was to identify hub genes and signaling pathways associated with bladder cancer (BC) utilizing centrality analysis and pathway enrichment analysis. The differentially expressed genes (DEGs) were screened from the ArrayExpress database between normal subjects and BC patients. Co-expression networks of BC were constructed using differentially co-expressed genes and links, and hub genes were investigated by degree centrality analysis of co-expression networks in BC. The enriched signaling pathways were investigated by Kyoto Encyclopedia of Genes and Genomes database analysis based on the DEGs. The hub gene expression in BC tissues was validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. A total of 329 DEGs were screened, including 147 upregulated and 182 downregulated genes. The co-expression network constructed between BC and normal controls consisted of 182 nodes and 434 edges, and the two genes in each gene pair were differentially co-expressed genes. Centrality analysis of co-expression networks suggested that the top 5 hub genes with high degree included lectin, galactoside-binding, soluble, 4 (LGALS4), protein tyrosine phosphatase, receptor type N2 (PTPRN2), transmembrane protease, serine 11E (TMPRSS11E), tripartite motif containing 31 (TRIM31) and potassium voltage-gated channel subfamily D member 3 (KCND3). Pathway analysis revealed that the 329 DEGs were significantly enriched in 5 terms (cell cycle, DNA replication, oocyte meiosis, p53 signaling pathway and peroxisome proliferator-activated receptor signaling pathway). According to RT-qPCR and western blot analysis, 4/5 hub genes were significantly expressed, including LGALS4, PTPRN2, TMPRSS11E, TRIM31; however, KCND3 was not significantly expressed. In the present study, 5 hub genes were successfully identified (LGALS4, PTPRN2, TMPRSS11E, TRIM31 and KCND3) and 5 biological pathways that may be underlying biomarkers for early diagnosis and treatment associated with bladder cancer were revealed.

Dataset Information

Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective.

Publications

Targeting hub genes and pathways of innate immune response in COVID-19: A network biology perspective.

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