Journal: Cell

Article Title: Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques

doi: 10.1016/j.cell.2020.10.005

Figure Lengend Snippet: Interferon and Inflammatory Pathways Increased by SARS-CoV-2 in BAL and Peripheral Blood of Infected Macaques (A) Circles plot representation of the GSEA NES of interferon and inflammatory pathways (GSEA: FDR ≤ 5%) increased or decreased by SARS-CoV-2 in BAL (left panel) and in peripheral blood (right panel) on days 1, 2, 4, 7, 10, and 14 compared to control animals. An NES greater than 0 (in red) corresponds to a pathway for which member genes are increased by SARS-CoV-2, and an NES below 0 (in blue) corresponds to a pathway for which member genes are decreased by SARS-CoV-2. The size and color of each circle is proportional to the NES, where color gradient ranging from blue (significantly decreased), gray (not significant: FDR ≥ 5%), or red (significantly increased). (B and C) Heatmaps of the log2 transformed fold change of interferon and inflammatory markers in BAL (B) and in peripheral blood (C) that are increased or decreased by SARS-CoV-2 on days 1, 2, 4, 7, 10, and 14 compared to baseline. Differential expression significance was assessed with a corrected p < 0.05 using Benjamini-Hochberg (BH) method. (D) Heatmaps of log2 transformed fold change expression in serum (proteomics) of interferon genes, increased (in red gradient), decreased (in blue gradient), and white (not significant), on days 1, 2, 4, 10, and 14 compared to baseline. Differential expression significance was assessed with a corrected p < 0.05 using BH method. (E and F) IHC shows increase of MX1 and pSTAT3 on day 2 or day 4 following SARS-CoV-2 challenge. Serial sections of lung tissue showed increased expression of MX1 (type 1 interferon response gene) (E) and phosphorylated STAT3 (Phospho-STAT3 (F). Scale bars, 100 μm. See also Figure S4 .

Article Snippet: The SomaScan® Platform for proteomics profiling uses 4979 SOMAmer® reagents, single-stranded DNA aptamers, to 4776 unique Human Protein Targets ( https://www.somalogic.com/wp-content/uploads/2016/08/SSM-002-Rev-3-SOMAscan-Technical-White-Paper.pdf ).

Techniques: Infection, Transformation Assay, Expressing

Journal: Cell

Article Title: Vascular Disease and Thrombosis in SARS-CoV-2-Infected Rhesus Macaques

doi: 10.1016/j.cell.2020.10.005

Figure Lengend Snippet: Cytokines and Chemokines Up- or Downregulated by SARS-CoV-2 in BAL, Peripheral Blood, and Serum of Infected Macaques (A and B) (Left panels) Heatmaps of log2 transformed fold change expression of individual cytokines increased (in red gradient), decreased (in blue gradient), or white (not significant) in BAL (A) and peripheral blood (B) on days 1, 2, 4, 7, 10, and 14 compared to baseline. (Right panels) Heatmaps of the GSEA NES of cytokines’ signaling pathways increased (in red gradient), decreased (in blue gradient), or white (not significant) in BAL (A) and peripheral blood (B) on days 1, 2, 4, 7, 10, and 14 compared to baseline. All individual cytokines were significant with a p < 0.05 for at least one time point post-challenge compared to baseline and all cytokines’ signaling pathways were significant with a GSEA nominal p < 0.05 for at least one time point post-challenge compared to baseline. Star symbol indicates individual cytokines or chemokines and pathways that remain significant after correction for multiple comparisons (BH method) or using a FDR of <5%. (C and D) Enrichment plot showing differentially expressed genes (DEGs) that contribute to the positive enrichment of the IL6-JAK-STAT3 signaling pathway on day 2 in BAL (C) and peripheral blood (D) of infected macaques. Plot of the running sum for pathway score in the dataset, including the location of the maximum ES and the leading-edge subset. The red plot shows the ES for the gene set as the analysis walks down the ranked list. The score at the peak of the plot (the score furthest from 0.0) is the ES for the gene set. The small black bars on the x axis show where the members of the gene set appear in the ranked list of genes. The leading-edge subset of a gene set is the subset of members that contribute most to the ES. The leading genes were shown for each plot. (E and F) IHC shows increased expression of IL-6 (E) and IL-10 (F) on day 2 or day 4 following SARS-CoV-2 challenge. Scale bars, 100 μm. (G) Heatmaps of log2 transformed fold change expression in serum (proteomics) of cytokines and chemokines increased (red gradient), decreased (blue gradient), and white (not significant), on days 1, 2, 4, 10, and 14 following challenge. Differential expression significance was assessed using a BH-corrected p < 0.05. (H) Cytokine levels measured by the Luminex assay in BAL (top panel) and in serum (lower panel) increased by SARS-CoV-2 in rhesus macaques on days 1, 2, 4, 7, 10, 14, or 35. All the cytokines and chemokines that are significant (Wilcoxon-Mann-Whitney test, p < 0.05) for at least one time point were shown on the heatmaps. Color gradient ranging from white (not significant) to red (highly significant) corresponds to the log2 transformation of the fold change of cytokines’ median levels compared to baseline. See also and .

Article Snippet: The SomaScan® Platform for proteomics profiling uses 4979 SOMAmer® reagents, single-stranded DNA aptamers, to 4776 unique Human Protein Targets ( https://www.somalogic.com/wp-content/uploads/2016/08/SSM-002-Rev-3-SOMAscan-Technical-White-Paper.pdf ).

Techniques: Infection, Transformation Assay, Expressing, Luminex, MANN-WHITNEY