Blood transcriptomics analysis offers insights into variant-specific immune response to SARS-CoV-2.

Publication date: Feb 02, 2024

Bulk RNA sequencing (RNA-seq) of blood is typically used for gene expression analysis in biomedical research but is still rarely used in clinical practice. In this study, we propose that RNA-seq should be considered a diagnostic tool, as it offers not only insights into aberrant gene expression and splicing but also delivers additional readouts on immune cell type composition as well as B-cell and T-cell receptor (BCR/TCR) repertoires. We demonstrate that RNA-seq offers insights into a patient’s immune status via integrative analysis of RNA-seq data from patients infected with various SARS-CoV-2 variants (in total 196 samples with up to 200 million reads sequencing depth). We compare the results of computational cell-type deconvolution methods (e. g., MCP-counter, xCell, EPIC, quanTIseq) to complete blood count data, the current gold standard in clinical practice. We observe varying levels of lymphocyte depletion and significant differences in neutrophil levels between SARS-CoV-2 variants. Additionally, we identify B and T cell receptor (BCR/TCR) sequences using the tools MiXCR and TRUST4 to show that-combined with sequence alignments and BLASTp-they could be used to classify a patient’s disease. Finally, we investigated the sequencing depth required for such analyses and concluded that 10 million reads per sample is sufficient. In conclusion, our study reveals that computational cell-type deconvolution and BCR/TCR methods using bulk RNA-seq analyses can supplement missing CBC data and offer insights into immune responses, disease severity, and pathogen-specific immunity, all achievable with a sequencing depth of 10 million reads per sample.

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Concepts Keywords
Biomedical Bcr
Cbc Blood
Depletion Bulk
Mixcr Cell
Trust4 Depth
Immune
Insights
Offers
Reads
Rna
Sars
Seq
Sequencing
Specific
Tcr

Semantics

Type Source Name
disease IDO blood
disease IDO immune response
disease IDO cell
drug DRUGBANK Gold
disease IDO pathogen
drug DRUGBANK Coenzyme M
disease MESH viral infection
disease MESH infection
pathway REACTOME Immune System
disease MESH Kidney Diseases
disease VO USA
disease MESH tumor
disease VO effective
disease MESH COVID 19
disease VO time
drug DRUGBANK Etoperidone
disease VO population
disease VO Viruses
drug DRUGBANK Pentaerythritol tetranitrate
disease MESH infectious diseases
disease IDO object
disease MESH Hepatitis
disease MESH glioma
pathway KEGG Glioma
disease MESH stroke
disease MESH systemic lupus erythematosus
pathway KEGG Systemic lupus erythematosus
drug DRUGBANK Mycophenolate mofetil
disease MESH Arthritis
disease MESH sequelae
disease VO vaccination
drug DRUGBANK (S)-Des-Me-Ampa
disease MESH Allergy
disease VO report
disease MESH Myelodysplastic syndrome
disease MESH pancytopenia
disease VO Gap
drug DRUGBANK Cladribine
disease VO efficiency
drug DRUGBANK Huperzine B
disease MESH idiopathic pulmonary fibrosis

Original Article

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