Figure 2. Integrative analysis revealing virus-host interactome networks and potential clinical relevance of identified host factors.

(a) Protein-protein interactome (PPI) networks between viral proteins and host factors identified by the dropout screen. 229 interactions between 26 SARS-CoV-2 proteins (red diamonds) and 147 human proteins (circles; depleted hits: blue; enriched hits: yellow) were found. The color of edge indicates the type of interaction (purple: host-host PPI; orange: viral-viral PPI; grey: host-viral PPI) and the thickness of edge indicates the count number of published datasets. (b) RNA-protein interactome networks between the viral RNA and host factors identified by the dropout screen. SARS-CoV-2 viral RNA was indicated as the red diamond; identified host factors were represented as circles (enriched hits: yellow; depleted hits: blue). The interaction between RNA and identified host factors were indicated as different edge types (colors: literature; thickness: count number of published manuscripts). (c) Gene variations in multiple identified host factors are associated with disease severity in COVID-19 patients. The Genome-Wide Association Study (GWAS) between variants of identified host factors and clinical features was performed by using the COVID19-hgGWAS meta-analyses. “Hospitalized” indicates that single nucleotide polymorphisms (SNPs) of the identified host factors were related to the hospitalized COVID-19 patients, which were labeled with blue dots. “Critically-ill” indicates SNPs of the identified host factors were related to COVID-19 patients with particularly severe respiratory symptoms, which were labeled with red dots. The names of enriched genes and depleted genes were labeled in red and green, respectively. (d) A volcano plot showing the changes of mRNA expression of identified host factors in epithelial cells from COVID-19 patients with and without severe illness. Multiple scRNA-seq datasets obtained from cells in bronchoalveolar lavage fluid of COVID-19 patients were extracted. COVID-19 patients with mild symptoms or hospitalized in the ward were stratified in the mild group, whereas COVID-19 patients with severe symptoms or hospitalized in the intensive care unit (ICU) were stratified in the severe group. The fold change of gene expression and p value were calculated. Identified pro-viral factors and anti-viral factors which are differentially expressed (p<0.05) in these two groups were highlighted with red and green dots, respectively.