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. 2021 Sep;11(9):e534.
doi: 10.1002/ctm2.534.

Host transcriptional response to SARS-CoV-2 infection in COVID-19 patients

Nitesh Kumar Singh  1 , Surabhi Srivastava  1 , Lamuk Zaveri  1 , Thrilok Chander Bingi  2 , Rajarao Mesipogu  2 , Santosh Kumar V  1 , Namami Gaur  1 , Nikhil Hajirnis  1 , Pratheusa Machha  1   3 , Sakshi Shambhavi  1   3 , Shagufta Khan  1 , Mamilla Soujanya  1   3 , Tulasi Nagabandi  1 , Rakesh K Mishra  1 , Karthik Bharadwaj Tallapaka  1 , Divya Tej Sowpati  1
Affiliations

Host transcriptional response to SARS-CoV-2 infection in COVID-19 patients

Nitesh Kumar Singh et al. Clin Transl Med. 2021 Sep.
No abstract available

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Differentially expressed genes (DEGs) and their expression in COVID‐19 patients compared to controls. (A) Principal component analysis representing the 36 COVID‐19 positive (red) and 5 negative samples (blue). Principal component 1 plotted on the x‐axis explains 34% of the variance and principal component 2 on the y‐axis explains 21% variance in the transcriptomic profiles. (B) Pie chart of biotype composition of DEGs. Only the top five categories for upregulated and downregulated genes are shown. Most of the upregulated genes are protein‐coding but the highest percentage of downregulated genes are lncRNAs. (C) Heatmap of the significantly expressed protein coding genes (rlog transformed expression values). Each bar marks the expression level of a gene from highest (red) to lowest (blue) as per the scale on the right. Sample names are indicated on the x‐axis (clustered by negative and then positive samples) and their metadata is shown on the top. “Condition” indicates COVID‐19 negative (gold bar) or positive (blue bar) status, while “Severity” indicates whether the patients needed ICU intervention (ICU, green bars) or were discharged from the general ward (W, dark blue bars). The Y‐axis bar on the left marks the number of upregulated protein coding genes (orange) followed by the downregulated protein coding genes (pink) in patients compared to the controls
FIGURE 2
FIGURE 2
Functional enrichment analysis for protein coding genes (220 upregulated and 3252 downregulated) in COVID‐19 patients compared to controls. (A) Top 10 enriched GO terms associated with upregulated genes (blue) and downregulated genes (red), based on adjusted p‐value (p.adj) values. (B) Interaction network showing enriched KEGG pathways associated with upregulated genes (blue nodes) and downregulated genes (red nodes). Nodes sharing 30% or more genes are connected by edges whose thickness represents the percentage of common genes. Size of the node represents the number of genes in that pathway (ranging from 4 to 136). (C) Protein–protein interactions of 19 genes showing a tightly connected network involved in “innate immune response” (red nodes), “defense response to virus” (blue nodes), and “type I interferon signaling pathway” (green nodes). These genes were upregulated during COVID‐19 infection in our analysis as well as in other published datasets (Table S6). Edges depict both functional and physical associations. Edge thickness indicates the confidence in the interaction. All active interaction sources in the STRING database are considered. The minimum interaction score for an edge is set at a high confidence level of 0.7. (D) Protein–protein interactions of 55 genes showing tightly connected clusters of genes involved in “cognition” (red nodes), “learning and memory” (blue nodes), and “sensory perception” (green nodes). These genes were involved in four addiction‐related pathways. Edges depict both functional and physical associations. Edge thickness indicates the confidence in the interaction. All active interaction sources in the STRING database are considered. The minimum interaction score for an edge is set at a high confidence level of 0.7
FIGURE 3
FIGURE 3
Distribution of expression data and enrichment analysis of differentially expressed protein coding genes closest to lncRNA. (A) Distribution of expression value (rlog transformed) for pseudogenes, lncRNAs, and protein‐coding genes displayed in the form of boxplot. All the pseudogenes, lncRNAs, and protein‐coding genes are shown on the left side of the plot, while differentially expressed genes are shown on the right side of the plot. Median of the distribution is represented by a horizontal line and whiskers are extended to 1.5 times interquartile range. (B) Schematic showing the method employed to categorize differentially expressed lncRNAs. The lncRNAs are divided into eight groups based on their location––genomic strand and distance to their closest differentially expressed protein coding gene. Number of lncRNA and their closest protein coding genes for each category is shown in the table. Most of the lncRNAs were on the antisense strand and overlapped with the cognate gene or its promoter. (C) GO enrichment analysis of the nearest protein coding genes associated with the differentially expressed lncRNAs. Enriched terms were identified only when the associated lncRNA overlapped with the cognate gene or its promoters. Only top 10 enriched terms, based on adjusted p‐value (p.adj) values, are plotted. Size of dots represents the number of genes and color signifies p.adj value
FIGURE 4
FIGURE 4
Enriched GO processes and KEGG pathways associated with significant DEGs. Volcano plot showing rlog transformed expression values of all the genes. Each gene is plotted based on the log2 fold change value (X‐axis) and –log10 adjusted p‐value (Y‐axis). Vertical dashed line (absolute (log2 fold change) = 1) and horizontal dashed line (padj = 0.05) show the criteria set for defining significant DEGs. Genes not changing significantly are colored gray. Upregulated genes (colored red) are on the right side of the plot, while downregulated genes (colored blue) are on the left side of the plot. Genes from significantly enriched GO terms and KEGG pathways are highlighted. For example, genes labeled as “Interferon related” are associated with the GO terms “type I interferon signaling pathway” and “cellular response to type I interferon.” Genes labeled as “Response to virus” are associated with the GO terms “defense response to virus” and “response to virus.” Genes marked as “Addiction related” are from four enriched KEGG pathways, namely, “Nicotine addiction,” “Morphine addiction,” “Cocaine addiction,” and “Amphetamine addiction.” The other labels correspond to genes from the KEGG pathway “Insulin secretion” and “Olfactory transduction”
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