Fig. 3: Viral-host PPIs and host responses in saliva from SARS-CoV-2 ancestral vs. variant infections. | Nature Communications

Fig. 3: Viral-host PPIs and host responses in saliva from SARS-CoV-2 ancestral vs. variant infections.

From: Human protein interaction networks of ancestral and variant SARS-CoV-2 in organ-specific cells and bodily fluids

Fig. 3

a CF-MS scoring pipeline identified reconfigured host-viral or host-host PPIs from 1128 SEC (size-exclusion chromatography) fractions using soluble protein extracts from saliva of healthy individuals (n = 3) and patients infected with ancestral (n = 3), Alpha (n = 2), Delta (n = 2), and Omicron (n = 2) variants. b Overlap of high-confidence (HC) host-viral PPIs detected via AP-MS in human cell lines and CF-MS in ancestral SARS-CoV-2-infected patient saliva. Host-viral PPIs also include those detected as high-confidence in the AP-MS dataset but below the CF-MS threshold, and vice versa. c Distribution of protein abundance (MS2 spectral counts) and viral-host PPIs across SARS-CoV-2 proteins detected by CF-MS. d Viral-host PPIs identified in SARS-CoV-2-infected patient saliva via CF-MS, and supported by AP-MS in human cell lines, analyzed with and without (i.e., All) RF score thresholds. e Scatterplot (left) showing Pearson correlation coefficients (PCCs) for co-eluting human protein pairs in saliva from SARS-CoV-2-infected vs. healthy or variant-infected patients at various P-value thresholds based on PCC score differences and two-sided Z-score transformation. Histogram (right) displays significantly differential (DF) human protein pairs at P ≤ 1.0e−5 and BH-adjusted FDR ≤ 5.0e−4 in the indicated comparisons. f Heatmap of positive and negative DF correlations in co-eluted human protein pairs from SARS-CoV-2- vs. healthy or variant-infected saliva. g Bar plot of positive and negative DF correlations of human protein pairs between SARS-CoV-2- and variant-infected individuals. h Specificity of human protein interaction pairs across all three variants. i GO biological term enrichment for human proteins interacting more or less specifically with variants. P-value from a one-sided Fisher exact test, and adjusted for FDR ≤ 5e−2 with the BH method. j Correlation profiles (autocorrelation) of co-eluted human protein interactions between SARS-CoV-2 and variants, categorized as high (>0.25) or low (<0.25), with zoom-in examples. Source data are provided as a Source Data file.

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