Single Cell Analysis Uncovers Mechanisms of Pathogen Response

Single Cell Analysis Uncovers Mechanisms of Pathogen Response

Table of Contents

June 27, 2022

GWAS and Disease Risk

Genome-wide association studies (GWAS) have successfully identified thousands of genetic variants associated with diseases. However, elucidating the molecular mechanisms through which a given genetic variant influences disease risk and disease response remains a challenge.

Some variants can regulate expression of other genes, a mechanism found in a recent paper in Nature by Oelen et. al. when studying how gene expression changes upon pathogen exposure. After performing single-cell RNA-sequencing (scRNA-seq) on 1.3M peripheral blood mononuclear cells from 120 individuals exposed to three different pathogens, the authors found that cell type plays the largest role in pathogen-responsive changes to gene expression, rather than specificity to pathogen type.

Single Cell Analysis Reveals Context-Specific Gene Expression Changes after Pathogen Exposure

After performing differential expression analysis, the number of differentially expressed genes was compared between the different pathogen stimulations at the same time points. Interestingly, the strongest differences in gene expression were observed between myeloid cells (monocytes and DCs) and CD4+/CD8+ T cells. While myeloid cells showcased the highest number of differentially expressed genes, CD4+ and CD8+ T cells showed the lowest.

In myeloid cells, over 70% of the genetic variants that were responsive to pathogen exposure were also involved in regulating the expression of related genes, representing widespread gene expression changes in response to pathogens in a non-pathogen-specific manner.

Outsourcing Bioinformatics Analysis

Single-cell RNA sequencing is exploding in popularity as a molecular biology research tool. However, interpreting single-cell RNA-seq data is a challenging computational and bioinformatic task. Outsourcing your bioinformatic analysis to experts like our team at Bridge Informatics helps eliminate common challenges with these projects. If you’re interested, book a free discovery call with us today to discuss your project needs.

Jenn Martinez, Project Manager, Bridge Informatics

Jenn has a Master’s in Bioinformatics and works as a Project Manager at Bridge Informatics, a professional services firm that helps biotech customers implement advanced techniques in the management and analysis of genomic data. Bridge Informatics focuses on data mining, machine learning, and various bioinformatic techniques to discover biomarkers and companion diagnostics. If you’re interested in reaching out, please email [email protected] or [email protected].


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