The transcriptomic profiling of COVID-19 compared to SARS, MERS, Ebola, and H1N1

COVID-19 pandemic is a global crisis that threatens our way of life. As of April 29, 2020, COVID-19 has claimed more than 200,000 lives, with a global mortality rate of ~7% and recovery rate of ~30%. Understanding the interaction of cellular targets to the SARS-CoV2 infection is crucial for therapeutic development. Therefore, the aim of this study was to perform a comparative analysis of transcriptomic signatures of infection of COVID-19 compared to different respiratory viruses (Ebola, H1N1, MERS-CoV, and SARS-CoV), to determine unique anti-COVID1-19 gene signature. We identified for the first time molecular pathways for Heparin-binding, RAGE, miRNA, and PLA2 inhibitors, to be associated with SARS-CoV2 infection. The NRCAM and SAA2 that are involved in severe inflammatory response, and FGF1 and FOXO1genes, which are associated with immune regulation, were found to be associated with a cellular gene response to COVID-19 infection. Moreover, several cytokines, most significantly the IL-8, IL-6, demonstrated key associations with COVID-19 infection. Interestingly, the only response gene that was shared between the five viral infections was SERPINB1. The PPI study sheds light on genes with high interaction activity that COVID-19 shares with other viral infections. The findings showed that the genetic pathways associated with Rheumatoid arthritis, AGE-RAGE signaling system, Malaria, Hepatitis B, and Influenza A were of high significance. We found that the virogenomic transcriptome of infection, gene modulation of host antiviral responses, and GO terms of both COVID-19 and Ebola are more similar compared to SARS, H1N1, and MERS. This work compares the virogenomic signatures of highly pathogenic viruses and provides valid targets for potential therapy against COVID-19.

Supplementary tables and figures

Figure 1 : Significant DEGs across the five transcriptomic profiles , corresponding genes, chromosome locations, gene expression  and significance scores. The DEGs related genes and chromosomal location (A). The DEGs information regarding host response to COVID-19 (B), Ebola (C), MERS-CoV (D) , H1N1 (E) and SARS-CoV (F) viral infections. The pvalues were scaled were scaled across gene profiles according to maximum and minimum values (ppvalue). The circles size and color is linked to DEGs significance and gene expression (LogFC) scores, respectively.

Figure 2 : Analysis of the gene enrichment of DEGs correlated with the host response to COVID-19. Categories of GO terms (A), significance scores (-10log-pvalue) (B), and number of associated DEGs (C). The COVID-19-associated DEGs  (D), status across the studied infectious diseases (E), and selected linked GO terms (F).

Figure 3: The Venn diagram of viral associated genes. The number of uniquely shared genes associated with the host response to COVID-19, Ebola, H1N1, MERS-CoV, and SARS-CoV viral infections.

Figure 4: The Venn diagram of viral associated GO terms. The number of uniquely shared GO terms of DEGs associated with the host response across COVID-19, Ebola, H1N1, MERS-CoV, and SARS-CoV viral infections.

Figure 5: The PPIs network of DEGs associated with COVID-19. The PPI of host expressed DEGs under COVID-19 infection. DEGs shared between COVID-19 and Ebola, H1N1, MERS-CoV, and SARS-CoV are color-coded according to kind of infection. The gene node size is relative to its interaction activity. DEGs are collected in different groups according to their level of interaction activity.

Figure 6: The PPIs network and gene enrichment analysis of highly interactive genes associated with COVID-19.

Figure S1 : The PPI network and gene enrichment analysis of the 173 genes that characterized the host response of COVID-19.

Figure S2: The PPI network and gene enrichment analysis of the 58 genes that are uniquely shared between COVID -19 and Ebola viral infections .

Figure S3 : The PPI network and gene enrichment analysis of the 51 genes that are uniquely shared between COVID-19 and MERS-CoV viral infections.

Figure S4 : The PPI network and gene enrichment analysis of the 31 genes that are uniquely shared between COVID-19, Ebola, and MERS-CoV  viral infections.

Figure S5 : The gene expression heatmap of genes COVID-19 shares with different viral infections.

Figure S6 : The PPI network and gene enrichment analysis of genes that are differentially expressed across studied viral infections and shared with COVID-19.

Table S1 : The data information used in this study.

Table S2: The information of DEGs associated the host response of COVID-19, Ebola, H1N1, MERS-CoV, and SARS-CoV viral infections.

Table S3: The Venn analysis results of DEGs and GO terms uniquely shared across of COVID-19, Ebola, H1N1, MERS-CoV, and SARS-CoV viral infections.

Table S4: Selected gene enrichment analysis of uniquely shared group of genes across the host response of COVID-19, Ebola, H1N1, MERS-CoV, and SARS-CoV viral infections.

Table S5: The gene expression information of DEGs that COVID-19 share with the studied infectious diseases.

Table S6: Selected gene enrichment analysis of uniquely shared group of GO terms across the host response of COVID-19 and studied viral infections.