Exploring changes in gene expression and associated biological pathways in individuals with COVID-19
The following case study features published data from Ziegler et al., 2021, Cell.
Background and Study Aim
Previously, a consortium of researchers, including scientists and clinicians from The University of Mississippi Medical Center (Jackson Mississippi), published a study investigating cellular phenotypes during early SARS-CoV-2 infection by profiling nasal mucosa using single-cell RNA sequencing of a cohort of 58 healthy and COVID-19 participants (Ziegler et al., 2021, Cell). Subsequently, Fios Genomics were involved in the analysis of RNA sequencing data derived from PBMCs from a subset of this cohort with the aim of exploring changes in gene expression between healthy and infected individuals and the corresponding dysregulated biological functions and pathways.
Experimental Design
The cohort subset comprised ten healthy individuals and ten COVID-19 patients. The COVID-19 cases varied in severity, defined by the level of required respiratory support, a measurement outlined in the World Health Organization guidelines for COVID-19 classification. A corresponding score was given, ranging from 0 (control), 1-5 (mild/moderate) and 6-8 (severe). Most COVID-19 cases in the cohort were classified as mild to moderate. Other clinical and demographic information were provided, including age, sex, BMI, race/ethnicity, the presence of co-morbidities, and for the infected group, symptoms of COVID-19, whether the patient required hospitalisation and if infection resulted in death. Clinical/demographic factors relating to all participants were evenly distributed among both the healthy and infected groups.
Results
A total of 101 genes were found to be significantly (FDR-adjusted P < 0.05) differentially expressed between healthy and COVID-19 participants: 77 genes were down-regulated and 24 were up-regulated in COVID-19 cases compared to controls. A large number of down-regulated genes encoded ribosomal proteins. Accordingly, the Reactome pathways and Gene Ontology (GO) terms most significantly enriched for genes that were down-regulated in COVID-19 patients were related to translation, with “Viral mRNA Translation” among the most significant. The relationship between SARS-CoV-2 and ribosomal function has previously been described in the literature (Wei and Hu., 2022, Life; Tsiambas et al., 2021, Front Mol Biosci) and our findings were consistent with the viral infection inhibiting the host mRNA translation to favour SARS-CoV-2 mRNA transcripts (Zhang et al., 2022, Front Immunol). In addition, one of the most significantly up-regulated genes was CCR2, which is in line with the results of a recent study identifying CCR2 signalling as an immune response mechanism through which SARS-CoV-2 infection can be restricted (Vanderheiden et al., 2021, mBio).
Overall, gene expression changes identified were in agreement with previously reported findings in COVID-19 studies. This work illustrates how changes in biological pathways caused by COVID-19 can be interrogated using transcriptome wide approaches. If you are interested in a similar project – Fios Genomics can help! Contact us today.
Sources
Tsiambas et al., 2021, Front Mol Biosci
