Co-expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19 Infection

Yuan, J.; Fan, d.; Xue, Z.; Qu, J.; Su, J.

doi:10.1101/2020.07.23.216770

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bioRxiv · 10.1101/2020.07.23.216770

Co-expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19 Infection

Yuan, J.·Fan, d.·Xue, Z.·Qu, J.·Su, J.

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Abstract

The Coronavirus disease 2019 (COVID-19) pandemic severely challenges public health and necessitates the need for increasing our understanding of COVID-19 pathogenesis, especially host factors facilitating virus infection and propagation. Here, the co-expression network was constructed by mapping the well-known ACE2, TMPRSS2 and host susceptibility genes implicated in COVID-19 GWAS onto a cornea, retinal pigment epithelium and lung. We found a significant co-expression module of these genes in the cornea, revealing that cornea is potential extra-respiratory entry portal of SARS-CoV-2. Strikingly, both co-expression and interaction networks show a significant enrichment in mitochondrial function, which are the hub of cellular oxidative homeostasis, inflammation and innate immune response. We identified a corneal mitochondrial susceptibility module (CMSM) of 14 mitochondrial genes by integrating ACE2 co-expression cluster and SARS-CoV-2 interactome. Gene ECSIT, as a cytosolic adaptor protein involved in inflammatory responses, exhibits the strongest correlation with ACE2 in CMSM, which has shown to be an important risk factor for SARS-CoV-2 infection and prognosis. Our co-expression and protein interaction network analysis uncover that the mitochondrial function related genes in cornea contribute to the dissection of COVID-19 susceptibility and potential therapeutic interventions.

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Yuan, J., Fan, d., Xue, Z., Qu, J., Su, J.. 2020-07-24. Co-expression of Mitochondrial Genes and ACE2 in Cornea Involved in COVID-19 Infection. https://doi.org/10.1101/2020.07.23.216770

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