Figure 1.
Transcriptome analysis of RNA isolated from SARS-CoV-2–positive NP swabs. Related to Fig. S1 and Table S1, Table S2, Table S3, Table S4, Table S5, and Table S6. (A) Volcano plot showing significantly differentially expressed protein-coding genes based on RNA-seq of NP swab RNA from SARS-CoV-2 patients (n = 30) compared with control SARS-CoV-2–negative subjects (n = 8). Transcripts with FC > 2 and adjusted P value < 0.05 are highlighted in red. (B) Top 20 Ingenuity pathways enriched in SARS-CoV-2–positive patients compared with controls based on 1,770 differentially expressed RNAs. P value and Z score for each pathway are indicated on the x axis. Pathways related to IFN and IFN regulatory factor signaling are highlighted in blue. NK, natural killer; Th, T helper; NO, nitric oxide; IRF, IFN regulatory factor. (C) Transcription factor–binding sites associated with NP transcripts enriched in SARS-CoV-2–positive patients compared with controls. Bars show strength of association of motifs/tracks with enriched transcripts, indicated by normalized enrichment score (NES). The y axis label indicates top transcription factor associated with each cluster of motifs (M) or tracks (T) and the cluster code. The number of enriched transcripts associated with each track/motif is indicated to the right of each bar. Transcription factors associated with the IFN response are highlighted in blue. (D) Graphical summary of pathways and regulators enriched based on Ingenuity Pathway Analysis of differentially expressed genes enriched in NP RNA of SARS-CoV-2–positive patients compared with controls. Colored lines indicate relationship between nodes, with orange lines showing enhancement and blue arrows showing suppression of a biological process by an upstream regulator (e.g., IFNλ1→suppression of viral infection). (E) Heatmap showing relative expression level of the top 45 most significant differentially expressed genes in patients (left) or SARS-CoV-2–negative controls (right). Clinical characteristics of each patient are indicated by color: viral load (red = highest viral load/lowest Ct value, green = lowest viral load/highest Ct value); NP CXCL10 protein level (red = highest, green = lowest, white = data not available). Heatmap colors represent values from highest (red) to lowest (green) for viral load (based on Ct value), CXCL10 concentration (pg/ml), or gene expression level, scaled from minimum to maximum (green = 0; yellow = 0.5, red = 1) Patient characteristics indicated at the top of the graph include admission status (gray, outpatient; black, admitted), sex (blue, male; pink, female), and age (blue, <55 yr; purple, >60 yr); white, data not available. Outpt., outpatient. (F) Correlation between reads mapping to CXCL10 and reads mapping to other ISGs (IFIT2, OASL, and ISG15). (G) Correlation between reads mapping to CXCL10 and CXCL10 protein measured by ELISA in NP swab–associated viral transport medium. PRR, pattern recognition receptor; SLE, systemic lupus erythematosus; PKR, protein kinase R; iCOS-iCOSL, inducible T cell costimulator and inducible T cell costimulator ligand.

Transcriptome analysis of RNA isolated from SARS-CoV-2–positive NP swabs. Related to Fig. S1 and Table S1, Table S2, Table S3, Table S4, Table S5, and Table S6. (A) Volcano plot showing significantly differentially expressed protein-coding genes based on RNA-seq of NP swab RNA from SARS-CoV-2 patients (n = 30) compared with control SARS-CoV-2–negative subjects (n = 8). Transcripts with FC > 2 and adjusted P value < 0.05 are highlighted in red. (B) Top 20 Ingenuity pathways enriched in SARS-CoV-2–positive patients compared with controls based on 1,770 differentially expressed RNAs. P value and Z score for each pathway are indicated on the x axis. Pathways related to IFN and IFN regulatory factor signaling are highlighted in blue. NK, natural killer; Th, T helper; NO, nitric oxide; IRF, IFN regulatory factor. (C) Transcription factor–binding sites associated with NP transcripts enriched in SARS-CoV-2–positive patients compared with controls. Bars show strength of association of motifs/tracks with enriched transcripts, indicated by normalized enrichment score (NES). The y axis label indicates top transcription factor associated with each cluster of motifs (M) or tracks (T) and the cluster code. The number of enriched transcripts associated with each track/motif is indicated to the right of each bar. Transcription factors associated with the IFN response are highlighted in blue. (D) Graphical summary of pathways and regulators enriched based on Ingenuity Pathway Analysis of differentially expressed genes enriched in NP RNA of SARS-CoV-2–positive patients compared with controls. Colored lines indicate relationship between nodes, with orange lines showing enhancement and blue arrows showing suppression of a biological process by an upstream regulator (e.g., IFNλ1→suppression of viral infection). (E) Heatmap showing relative expression level of the top 45 most significant differentially expressed genes in patients (left) or SARS-CoV-2–negative controls (right). Clinical characteristics of each patient are indicated by color: viral load (red = highest viral load/lowest Ct value, green = lowest viral load/highest Ct value); NP CXCL10 protein level (red = highest, green = lowest, white = data not available). Heatmap colors represent values from highest (red) to lowest (green) for viral load (based on Ct value), CXCL10 concentration (pg/ml), or gene expression level, scaled from minimum to maximum (green = 0; yellow = 0.5, red = 1) Patient characteristics indicated at the top of the graph include admission status (gray, outpatient; black, admitted), sex (blue, male; pink, female), and age (blue, <55 yr; purple, >60 yr); white, data not available. Outpt., outpatient. (F) Correlation between reads mapping to CXCL10 and reads mapping to other ISGs (IFIT2, OASL, and ISG15). (G) Correlation between reads mapping to CXCL10 and CXCL10 protein measured by ELISA in NP swab–associated viral transport medium. PRR, pattern recognition receptor; SLE, systemic lupus erythematosus; PKR, protein kinase R; iCOS-iCOSL, inducible T cell costimulator and inducible T cell costimulator ligand.

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