Statistics of H2V data
Overall, H2V contains 332 PPIs, 131 DEPs, 232 DTPs, 1298 DPPs, 204 SAPs, and 10993 DEGs entries (Table 1). Specifically: there are 332 PPIs, 65 DEPs, 232 DTPs, 1298 DPPs, 204 SAPs, and 4012 DEGs in response to SARS-CoV-2 infection; there are 66 DEPs in response to SARS-CoV infection; and there are 6981 DEGs in response to MERS-CoV infection. The human-SARS-CoV-2 PPIs also include 27 SARS-CoV-2 proteins, with nsp5 mutant C145A considered as a unique protein.
Among the human proteins that respond to SARS-CoV-2 infection (Figure 1a): 10 proteins intersect between DEPs and DTPs; 3 proteins intersect between DEPs and SAPs; 6 proteins intersect between DEPs and DPPs; 5 proteins intersect between DTPs and SAPs; 26 proteins intersect between DTPs and DPPs; 5 proteins intersect between SAPs and DPPs; DEPs, DTPs, and SAPs share 1 protein; DEPs, SAPs, and DPPs share 1 protein as well. There is only 1 common protein between DEPs in response to SARS-CoV-2 and SARS-CoV infection (Figure 1b). The set of intersecting genes is larger than that of intersecting proteins. As shown in Figure 1c, there are 1497 intersecting genes between DEGs in response to SARS-CoV-2 and MERS-CoV infection.
Proteins/genes responding to SARS-CoV-2
The “SARS2” drop-down menu in the navigation bar of the website provides links to human proteins and genes that respond to SARS-CoV-2 infection. PPIs are shown in a table or as a network (Figure 2a-b). In the table of PPIs (Figure 2a), human-SARS-CoV-2 PPIs are put in rows, with other protein information shown in columns. For SARS-CoV-2 proteins, the corresponding genes are put in the “SARS2 gene” column. By clicking on a SARS-CoV-2 gene, its annotation will be shown in the embedded NCBI sequence viewer on the same web page (Figure 2c). UniProt identifiers, protein names, gene names, and HGNC identifiers of human proteins are also displayed in the PPIs table. The external links to the UniProt database and HGNC database can help users to study the proteins of their interests. The “Drug” column in the PPIs table can be used to retrieve drugs of a protein target from the DrugBank database. This feature would facilitate rapid discovery of candidate antiviral drugs. DEPs, DTPs, and DPPs are listed in a table in a similar format, so DPPs are taken as an example and demonstrated in Figure 2d. Compared to the PPIs table, SARS-CoV-2 columns are removed but a “Temporal profile” column is added. Clicking on the “Show” button of a protein in this column will display a plot showing how the protein phosphorylation changes over time and when the change reaches significance (Figure 2e). DEPs and DTPs also have a similar profile to show how the expression or translation of a protein dynamically changes over time, but only the DPPs profile is shown as an example. Because time series data is not available for SAPs, the log2 fold changes and p values are put in columns “log2FC” and “P-value” (Figure 2f). DEGs are also shown in a table, with links to the HGNC database, log2 fold changes, and p values put in columns (Figure 2g).
Proteins responding to SARS-CoV
All of the collected human proteins that respond to SARS-CoV infection are DEPs. The DEPs table can be accessed via the “DEPs” link on the “SARS1” drop-down menu in the navigation bar of the website. As can be seen from Figure 3, DEPs are listed in table rows, and the correlated information is listed in table columns.
Genes responding to MERS-CoV
All of the collected human genes that respond to MERS-CoV infection are DEGs. The DEGs table can be accessed by clicking on the “DEGs” link on the “MERS-CoV” drop-down menu in the navigation bar of the website. In the table, gene names, HGNC identifiers, and buttons to temporal profiles are given (Figure 4a). Users can click on the “Show” button of a DEG to see how its expression changes with time after MERS-CoV infection (Figure 4b).
Application case
H2V provides two easy-to-use utilities, one is “Drug finder” and the other is “Data animation”. The former one facilitates to find drugs that can target a given protein based on its UniProt accession number. If drug exists, drug name and DrugBank identifier will be displayed below the utility on the same page. For example, searching 9BYF1 will find drugs moexipril and SPP1148 (Figure 5a).
The data animation utility provides a concrete perception of the proteomic dynamics over a period (Figure 5b-5g). Compared to 2 h after SARS-CoV-2 infection, the number of DEPs and DTPs increased at 24 h after virus infection. The number of DPPs at 24 h is also larger than that at 0 h after SARS-CoV-2 infection. These trends give us a clear picture that the human body responds to SARS-CoV-2 infection by continuously activating protein biogenesis.