Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19
SARS-CoV-2 infections are highly correlated with the overexpression of pro-inflammatory cytokines in what is known as a cytokine storm, leading to high fatality rates. Such infections are accompanied by SIRS, ARDS, and sepsis, suggesting a potential link between the three phenotypes. Currently, litt...
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| Format: | Article |
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MDPI AG
2022-12-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/11/12/1827 |
| _version_ | 1797461330329862144 |
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| author | Ryan Christian Mailem Lemmuel L. Tayo |
| author_facet | Ryan Christian Mailem Lemmuel L. Tayo |
| author_sort | Ryan Christian Mailem |
| collection | DOAJ |
| description | SARS-CoV-2 infections are highly correlated with the overexpression of pro-inflammatory cytokines in what is known as a cytokine storm, leading to high fatality rates. Such infections are accompanied by SIRS, ARDS, and sepsis, suggesting a potential link between the three phenotypes. Currently, little is known about the transcriptional similarity between these conditions. Herein, weighted gene co-expression network analysis (WGCNA) clustering was applied to RNA-seq datasets (GSE147902, GSE66890, GSE74224, GSE177477) to identify modules of highly co-expressed and correlated genes, cross referenced with dataset GSE160163, across the samples. To assess the transcriptome similarities between the conditions, module preservation analysis was performed and functional enrichment was analyzed in DAVID webserver. The hub genes of significantly preserved modules were identified, classified into upregulated or downregulated, and used to screen candidate drugs using Connectivity Map (CMap) to identify repurposed drugs. Results show that several immune pathways (chemokine signaling, NOD-like signaling, and Th1 and Th2 cell differentiation) are conserved across the four diseases. Hub genes screened using intramodular connectivity show significant relevance with the pathogenesis of cytokine storms. Transcriptomic-driven drug repurposing identified seven candidate drugs (SB-202190, eicosatetraenoic-acid, loratadine, TPCA-1, pinocembrin, mepacrine, and CAY-10470) that targeted several immune-related processes. These identified drugs warrant further study into their efficacy for treating cytokine storms, and in vitro and in vivo experiments are recommended to confirm the findings of this study. |
| first_indexed | 2024-03-09T17:17:54Z |
| format | Article |
| id | doaj.art-127491a2a5d744c691df028e6432d5cb |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-09T17:17:54Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-127491a2a5d744c691df028e6432d5cb2023-11-24T13:24:13ZengMDPI AGBiology2079-77372022-12-011112182710.3390/biology11121827Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19Ryan Christian Mailem0Lemmuel L. Tayo1School of Chemical, Biological, and Materials Engineering and Sciences and School of Graduate Studies, Mapúa University, Manila City 1002, PhilippinesSchool of Chemical, Biological, and Materials Engineering and Sciences and School of Graduate Studies, Mapúa University, Manila City 1002, PhilippinesSARS-CoV-2 infections are highly correlated with the overexpression of pro-inflammatory cytokines in what is known as a cytokine storm, leading to high fatality rates. Such infections are accompanied by SIRS, ARDS, and sepsis, suggesting a potential link between the three phenotypes. Currently, little is known about the transcriptional similarity between these conditions. Herein, weighted gene co-expression network analysis (WGCNA) clustering was applied to RNA-seq datasets (GSE147902, GSE66890, GSE74224, GSE177477) to identify modules of highly co-expressed and correlated genes, cross referenced with dataset GSE160163, across the samples. To assess the transcriptome similarities between the conditions, module preservation analysis was performed and functional enrichment was analyzed in DAVID webserver. The hub genes of significantly preserved modules were identified, classified into upregulated or downregulated, and used to screen candidate drugs using Connectivity Map (CMap) to identify repurposed drugs. Results show that several immune pathways (chemokine signaling, NOD-like signaling, and Th1 and Th2 cell differentiation) are conserved across the four diseases. Hub genes screened using intramodular connectivity show significant relevance with the pathogenesis of cytokine storms. Transcriptomic-driven drug repurposing identified seven candidate drugs (SB-202190, eicosatetraenoic-acid, loratadine, TPCA-1, pinocembrin, mepacrine, and CAY-10470) that targeted several immune-related processes. These identified drugs warrant further study into their efficacy for treating cytokine storms, and in vitro and in vivo experiments are recommended to confirm the findings of this study.https://www.mdpi.com/2079-7737/11/12/1827bioinformaticscytokine stormdrug repurposinggene expressiongeneticssystems biology |
| spellingShingle | Ryan Christian Mailem Lemmuel L. Tayo Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 Biology bioinformatics cytokine storm drug repurposing gene expression genetics systems biology |
| title | Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 |
| title_full | Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 |
| title_fullStr | Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 |
| title_full_unstemmed | Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 |
| title_short | Drug Repurposing Using Gene Co-Expression and Module Preservation Analysis in Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS), Sepsis, and COVID-19 |
| title_sort | drug repurposing using gene co expression and module preservation analysis in acute respiratory distress syndrome ards systemic inflammatory response syndrome sirs sepsis and covid 19 |
| topic | bioinformatics cytokine storm drug repurposing gene expression genetics systems biology |
| url | https://www.mdpi.com/2079-7737/11/12/1827 |
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