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Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients

Background: SARS-COV2 virus detected in December 2019, and was considered a pandemic in March 2020 by the WHO. Symptoms range from asymptomatic to life threatening ones. Studying cell-cell interactions in patients' blood samples may lead to novel diagnosis and treatment approaches. Aim: This study a...

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Main Author: Elbaz, Ahmed
Format: Thesis
Published: AUC Knowledge Fountain 2021
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author Elbaz, Ahmed
author_browse Elbaz, Ahmed
author_facet Elbaz, Ahmed
author_sort Elbaz, Ahmed
collection Thesis
description Background: SARS-COV2 virus detected in December 2019, and was considered a pandemic in March 2020 by the WHO. Symptoms range from asymptomatic to life threatening ones. Studying cell-cell interactions in patients' blood samples may lead to novel diagnosis and treatment approaches. Aim: This study aims to analyze single-cell RNA sequencing data to identify differences in cell-cell communications between healthy and COVID patients and differentially expressed T-cells genes that contributed to immune system antiviral activity. Materials and methods: Single-Cell RNA sequencing data from seven COVID patients and five healthy individuals were collected from (GEO accession GSE155673). Cell types were identified and cell-cell interactions were inferred for each condition (healthy, moderate and severe COVID patients). Additionally, T cells differentially expressed genes between the three conditions were identified and pathways enrichment were performed. Results: Eight cell types were identified. Percentage of T cells decreased from 32.76% in healthy individuals to 16% in severe COVID cases. Cell-Cell interactions analysis revealed significant alterations among healthy, moderate, and severe conditions such as reduction of overall incoming signaling in T cells of severe cases. Additionally, SN signaling pathway was identified only in COVID cases, which in turn was found to be in IFN-γ reduction in distinct cell types. Pathways enrichment analysis identified IFN-γ signaling to be upregulated in moderate cases, and to be downregulated in severe ones. Protein interacting with IFN-γ also shows downregulation such as IRF1. However, the negative regulator of IFN-γ -SOCS3- was upregulated in COVID patients T cells. Conclusion: Cell-cell interactions alteration in COVID patients might have resulted in eliciting improper immune response. Not only, did T cells percentage decreased in severe COVID cases, but also T cells overall incoming signaling was decreased. Additionally, cell-cell interaction alteration might have played a significant role in suppressing antiviral response through IFN-γ reduction which might contribute to the observed severity of COVID cases.
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institution American University in Cairo (Egypt)
last_indexed 2026-06-10T12:35:50.652Z
license_str Not specified — see source repository
provenance_str_mv Harvested via OAI-PMH from AUC Knowledge Fountain — bepress
publishDate 2021
publishDateRange 2021
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spelling oai:fount.aucegypt.edu:etds-2668 Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients Elbaz, Ahmed Background: SARS-COV2 virus detected in December 2019, and was considered a pandemic in March 2020 by the WHO. Symptoms range from asymptomatic to life threatening ones. Studying cell-cell interactions in patients' blood samples may lead to novel diagnosis and treatment approaches. Aim: This study aims to analyze single-cell RNA sequencing data to identify differences in cell-cell communications between healthy and COVID patients and differentially expressed T-cells genes that contributed to immune system antiviral activity. Materials and methods: Single-Cell RNA sequencing data from seven COVID patients and five healthy individuals were collected from (GEO accession GSE155673). Cell types were identified and cell-cell interactions were inferred for each condition (healthy, moderate and severe COVID patients). Additionally, T cells differentially expressed genes between the three conditions were identified and pathways enrichment were performed. Results: Eight cell types were identified. Percentage of T cells decreased from 32.76% in healthy individuals to 16% in severe COVID cases. Cell-Cell interactions analysis revealed significant alterations among healthy, moderate, and severe conditions such as reduction of overall incoming signaling in T cells of severe cases. Additionally, SN signaling pathway was identified only in COVID cases, which in turn was found to be in IFN-γ reduction in distinct cell types. Pathways enrichment analysis identified IFN-γ signaling to be upregulated in moderate cases, and to be downregulated in severe ones. Protein interacting with IFN-γ also shows downregulation such as IRF1. However, the negative regulator of IFN-γ -SOCS3- was upregulated in COVID patients T cells. Conclusion: Cell-cell interactions alteration in COVID patients might have resulted in eliciting improper immune response. Not only, did T cells percentage decreased in severe COVID cases, but also T cells overall incoming signaling was decreased. Additionally, cell-cell interaction alteration might have played a significant role in suppressing antiviral response through IFN-γ reduction which might contribute to the observed severity of COVID cases. 2021-05-25T07:00:00Z thesis application/pdf https://fount.aucegypt.edu/etds/1644 https://fount.aucegypt.edu/context/etds/article/2668/viewcontent/Thesis_Ahmed_ElBaz.pdf https://fount.aucegypt.edu/context/etds/article/2668/filename/3/type/additional/viewcontent/Supplementary_file_1.xlsx https://fount.aucegypt.edu/context/etds/article/2668/filename/4/type/additional/viewcontent/Supplementary_file_2.xlsx https://fount.aucegypt.edu/context/etds/article/2668/filename/5/type/additional/viewcontent/Supplementary_file_3.xlsx Theses and Dissertations AUC Knowledge Fountain COVID-19 SARS-CoV2 IFNG Interferon-Gamma scRNA-seq cell-cell interactions T-cells adaptive immunity Interferons Biological Phenomena, Cell Phenomena, and Immunity Virus Diseases Viruses
spellingShingle COVID-19 SARS-CoV2 IFNG Interferon-Gamma scRNA-seq cell-cell interactions T-cells adaptive immunity Interferons
Biological Phenomena, Cell Phenomena, and Immunity
Virus Diseases
Viruses
Elbaz, Ahmed
Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients
title Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients
title_full Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients
title_fullStr Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients
title_full_unstemmed Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients
title_short Analysis of Single Cell RNA-seq Data Revealed Interferon Gamma Signaling Alteration in Severe COVID patients
title_sort analysis of single cell rna seq data revealed interferon gamma signaling alteration in severe covid patients
topic COVID-19 SARS-CoV2 IFNG Interferon-Gamma scRNA-seq cell-cell interactions T-cells adaptive immunity Interferons
Biological Phenomena, Cell Phenomena, and Immunity
Virus Diseases
Viruses
url https://fount.aucegypt.edu/etds/1644
https://fount.aucegypt.edu/context/etds/article/2668/viewcontent/Thesis_Ahmed_ElBaz.pdf
https://fount.aucegypt.edu/context/etds/article/2668/filename/3/type/additional/viewcontent/Supplementary_file_1.xlsx
https://fount.aucegypt.edu/context/etds/article/2668/filename/4/type/additional/viewcontent/Supplementary_file_2.xlsx
https://fount.aucegypt.edu/context/etds/article/2668/filename/5/type/additional/viewcontent/Supplementary_file_3.xlsx
work_keys_str_mv AT elbazahmed analysisofsinglecellrnaseqdatarevealedinterferongammasignalingalterationinseverecovidpatients