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pmid:34131597

A bioinformatics approach for identifying potential molecular mechanisms and key genes involved in COVID-19 associated cardiac remodeling.

Hamid Ceylan

Gene reports · 2021 doi:10.1016/j.genrep.2021.101246

Paper

complete

Experiment

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Data

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Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:34131597
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science-record
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2026-11-01T15:41:39Z
updated_at
2026-11-01T22:03:58Z
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paper object · 10 fields
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title
A bioinformatics approach for identifying potential molecular mechanisms and key genes involved in COVID-19 associated cardiac remodeling.
doi
10.1016/j.genrep.2021.101246
pmid
34131597
authors array · 1 item
[0]
Hamid Ceylan
journal
Gene reports
year
2021
abstract
In 2019 coronavirus disease (COVID-19), whose main complication is respiratory involvement, different organs may also be affected in severe cases. However, COVID-19 associated cardiovascular manifestations are limited at present. The main purpose of this study was to identify potential candidate genes involved in COVID-19-associated heart damage by bioinformatics analysis. Differently expressed genes (DEGs) were identified using transcriptome profiles (GSE150392 and GSE4172) downloaded from the GEO database. After gene and pathway enrichment analyses, PPI network visualization, module analyses, and hub gene extraction were performed using Cytoscape software. A total of 228 (136 up and 92 downregulated) overlapping DEGs were identified at these two microarray datasets. Finally, the top hub genes (FGF2, JUN, TLR4, and VEGFA) were screened out as the critical genes among the DEGs from the PPI network. Identification of critical genes and mechanisms in any disease can lead us to better diagnosis and targeted therapy. Our findings identified core genes shared by inflammatory cardiomyopathy and SARS-CoV-2. The findings of the current study support the idea that these key genes can be used in understanding and managing the long-term cardiovascular effects of COVID-19.
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DEGs between SARS-CoV-2 infected hiPSC-CMs and non-infected hiPSC-CMs were screened by using Genevestigator software (Hruz et al., 2008) and the GEO2R tool (Barrett et al., 2013). p-Value <0.05 and a |log2FC| ≥ 0.5 were defined as the cut-off criteria.
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sections[4] "Identification of DEGs" paragraph 2
quote
DEGs between SARS-CoV-2 infected hiPSC-CMs and non-infected hiPSC-CMs were screened by using Genevestigator software (Hruz et al., 2008) and the GEO2R tool (Barrett et al., 2013). p-Value <0.05 and a |log2FC| ≥ 0.5 were defined as the cut-off criteria.
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All data used in this study are available in the GEO repository.
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sections[13] "Data availability" paragraph 2
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All data used in this study are available in the GEO repository.
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RNA-Seq of Human iPSC-cardiomyocytes infected with SARS-CoV-2
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Gene expression profiling of human inflammatory Cardiomyopathy
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6
[1]
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62
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[1]
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52
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10
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11
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12
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The detailed information of the significantly enriched KEGG pathways for the up and downregulated DEGs.
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GO term and pathway enrichment analyses
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Table 2
caption
The detailed information of the significantly enriched KEGG pathways for the up and downregulated DEGs.
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[0] array · 3 items
[0]
KEGG pathway
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Genes in category
[2]
p-Value
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[0]
Upregulated DEGs
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[0]
Epstein-Barr virus infection
[1]
MAP2K3, CDKN1A, PSMD12, JUN, DDX58, EIF2AK2, HLA-E
[2]
5,80E-04
[3] array · 3 items
[0]
Influenza A
[1]
MAP2K3, DNAJB1, JUN, DDX58, HSPA6, EIF2AK2, TLR4
[2]
3,60E-03
[4] array · 3 items
[0]
Protein processing in endoplasmic reticulum
[1]
DNAJB1, HSPA6, EIF2AK2, CKAP4, UBE2J1, NFE2L2
[2]
1,50E-02
[5] array · 3 items
[0]
Pathways in cancer
[1]
CDKN1A, JUN, CCND1, CXCR4, FGF2, FOXO1, BIRC3, RUNX1, VEGFA
[2]
1,80E-02
[6] array · 3 items
[0]
Measles
[1]
CCND1, DDX58, HSPA6, EIF2AK2, TLR4
[2]
2,70E-02
[7] array · 3 items
[0]
Proteoglycans in cancer
[1]
CDKN1A, CCND1, ITPR2, FGF2, TLR4, VEGFA
[2]
2,80E-02
[8] array · 3 items
[0]
Hepatitis B
[1]
CDKN1A, JUN, CCND1, DDX58, TLR4
[2]
3,50E-02
[9] array · 3 items
[0]
Rheumatoid arthritis
[1]
JUN, TLR4, ATP6V1C1, VEGFA
[2]
3,90E-02
[10] array · 3 items
[0]
Bladder cancer
[1]
CDKN1A, CCND1, VEGFA
[2]
4,80E-02
[11] array · 1 item
[0]
[12] array · 1 item
[0]
Downregulated DEGs
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[0]
Parkinson's disease
[1]
COX7B, NDUFA6, ATP5A1, NDUFB1, PRKACA, SEPT5, COX7C, COX6A2
[2]
1,90E-06
[14] array · 3 items
[0]
Oxidative phosphorylation
[1]
COX7B, NDUFA6, ATP5A1, NDUFB1, COX7C, COX6A2, LHPP
[2]
1,90E-05
[15] array · 3 items
[0]
Alzheimer's disease
[1]
COX7B, NDUFA6, ATP5A1, NDUFB1, COX7C, COX6A2
[2]
7,10E-04
[16] array · 3 items
[0]
Huntington's disease
[1]
COX7B, NDUFA6, ATP5A1, NDUFB1, COX7C, COX6A2
[2]
1,30E-03
[17] array · 3 items
[0]
Non-alcoholic fatty liver disease (NAFLD)
[1]
COX7B, NDUFA6, NDUFB1, COX7C, COX6A2
[2]
3,90E-03
[18] array · 3 items
[0]
Cardiac muscle contraction
[1]
COX7B, MYL3, COX7C, COX6A2
[2]
4,10E-03
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Top 10 genes evaluated in the PPI network using five calculation methods and employing CytoHubba in Cytoscape. The overlapping hub genes in the top 10 by five ranked methods respectively in cytoHubba are highlighted in bold.
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PMC8192842
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10
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Identification and validation of hub genes
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Table 3
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Top 10 genes evaluated in the PPI network using five calculation methods and employing CytoHubba in Cytoscape. The overlapping hub genes in the top 10 by five ranked methods respectively in cytoHubba are highlighted in bold.
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[0] array · 10 items
[0]
Gene
[1]
MCC
[2]
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[3]
MNC
[4]
Gene
[5]
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[6]
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[7]
EcCentricity
[8]
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[9]
EPC
[1] array · 10 items
[0]
VEGFA
[1]
610.0
[2]
JUN
[3]
25.0
[4]
JUN
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26.0
[6]
JUN
[7]
0.17375
[8]
VEGFA
[9]
28.994
[2] array · 10 items
[0]
JUN
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609.0
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[3]
24.0
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VEGFA
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26.0
[6]
VEGFA
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0.17375
[8]
JUN
[9]
28.507
[3] array · 10 items
[0]
FGF2
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434.0
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20.0
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TLR4
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23.0
[6]
TLR4
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0.17375
[8]
CCND1
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27.439
[4] array · 10 items
[0]
CCND1
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382.0
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TLR4
[3]
20.0
[4]
CCND1
[5]
22.0
[6]
FGF2
[7]
0.17375
[8]
TLR4
[9]
26.957
[5] array · 10 items
[0]
CDKN1A
[1]
357.0
[2]
FGF2
[3]
17.0
[4]
FGF2
[5]
17.0
[6]
LGALS3
[7]
0.17375
[8]
FGF2
[9]
26.208
[6] array · 10 items
[0]
TLR4
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285.0
[2]
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16.0
[4]
CDKN1A
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17.0
[6]
BIRC3
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0.17375
[8]
CDKN1A
[9]
26.047
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[0]
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245.0
[2]
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16.0
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17.0
[6]
CXCR4
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0.17375
[8]
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24.942
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[0]
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216.0
[2]
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[3]
13.0
[4]
PRKACA
[5]
15.0
[6]
DDX58
[7]
0.17375
[8]
LGALS3
[9]
22.287
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[0]
PSMB8
[1]
202.0
[2]
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[3]
10.0
[4]
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13.0
[6]
HSPB3
[7]
0.17375
[8]
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[9]
22.271
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[0]
PSMD12
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198.0
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THY1
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12.0
[6]
ABCB1
[7]
0.17375
[8]
BIRC3
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21.898
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section[10]/table-wrap[1]#t0015
gaps array · 4 items
[0]
asset:data:geo:GSE150392 not downloaded
[1]
asset:data:geo:GSE150392 licence not read
[2]
asset:data:geo:GSE4172 not downloaded
[3]
asset:data:geo:GSE4172 licence not read
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partial
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method-1
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[0]
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centrality_scores
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pathway_enrich
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edge_list
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Network / pathway analysis
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[0]
pathway_enrich
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edge_list
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pathway enrichment
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Genevestigator software and the GEO2R tool
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quote
DEGs between SARS-CoV-2 infected hiPSC-CMs and non-infected hiPSC-CMs were screened by using Genevestigator software (Hruz et al., 2008) and the GEO2R tool (Barrett et al., 2013). p-Value <0.05 and a |log2FC| ≥ 0.5 were defined as the cut-off criteria.
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meta_analysis
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Automated Assays Laravel application and simulated adapters
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complete
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GSE4172
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GSE150392
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GSE4172
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[0]
All data used in this study are available in the GEO repository.
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The paper names GSE150392, GSE4172 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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pathway_enrich
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Complete file
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The main purpose of this study was to identify potential candidate genes involved in COVID-19-associated heart damage by bioinformatics analysis. Differently expressed genes (DEGs) were identified using transcriptome profiles (GSE150392 and GSE4172) downloaded from the GEO database. After gene and pathway enrichment analyses, PPI network visualization, module analyses, and hub gene extraction were performed using Cytoscape software. A total of 228 (136 up and 92 downregulated) overlapping DEGs were identified at these two microarray datasets. Finally, the top hub genes (FGF2, JUN, TLR4, and VEGFA) were screened out as the critical genes among the DEGs from the PPI network. Identification of critical genes and mechanisms in any disease can lead us to better diagnosis and targeted therapy. Our findings identified core genes shared by inflammatory cardiomyopathy and SARS-CoV-2. 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"verified", "reader": "read_table", "reader_status": "available", "identifier": "section[10]/table-wrap[1]#t0015", "version": null, "note": "Top 10 genes evaluated in the PPI network using five calculation methods and employing CytoHubba in Cytoscape. The overlapping hub genes in the top 10 by five ranked methods respectively in cytoHubba are highlighted in bold.", "structure": {"pmcid": "PMC8192842", "section_index": 10, "section_title": "Identification and validation of hub genes", "row_count": 11, "column_count": 10}, "table": {"label": "Table 3", "caption": "Top 10 genes evaluated in the PPI network using five calculation methods and employing CytoHubba in Cytoscape. The overlapping hub genes in the top 10 by five ranked methods respectively in cytoHubba are highlighted in bold.", "rows": [["Gene", "MCC", "Gene", "MNC", "Gene", "Degree", "Gene", "EcCentricity", "Gene", "EPC"], ["VEGFA", "610.0", "JUN", "25.0", "JUN", "26.0", "JUN", "0.17375", "VEGFA", "28.994"], ["JUN", "609.0", "VEGFA", "24.0", "VEGFA", "26.0", "VEGFA", "0.17375", "JUN", "28.507"], ["FGF2", "434.0", "CCND1", "20.0", "TLR4", "23.0", "TLR4", "0.17375", "CCND1", "27.439"], ["CCND1", "382.0", "TLR4", "20.0", "CCND1", "22.0", "FGF2", "0.17375", "TLR4", "26.957"], ["CDKN1A", "357.0", "FGF2", "17.0", "FGF2", "17.0", "LGALS3", "0.17375", "FGF2", "26.208"], ["TLR4", "285.0", "CDKN1A", "16.0", "CDKN1A", "17.0", "BIRC3", "0.17375", "CDKN1A", "26.047"], ["ITGAM", "245.0", "ITGAM", "16.0", "ITGAM", "17.0", "CXCR4", "0.17375", "ITGAM", "24.942"], ["AURKB", "216.0", "AURKB", "13.0", "PRKACA", "15.0", "DDX58", "0.17375", "LGALS3", "22.287"], ["PSMB8", "202.0", "PSMB8", "10.0", "AURKB", "13.0", "HSPB3", "0.17375", "CXCR4", "22.271"], ["PSMD12", "198.0", "THY1", "10.0", "PSMB8", "12.0", "ABCB1", "0.17375", "BIRC3", "21.898"]], "row_count": 11, "column_count": 10, "numeric_cells": 52, "header_rows": 1, "locator": "section[10]/table-wrap[1]#t0015"}}], "gaps": ["asset:data:geo:GSE150392 not downloaded", "asset:data:geo:GSE150392 licence not read", "asset:data:geo:GSE4172 not downloaded", "asset:data:geo:GSE4172 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "PPI"}}, {"id": "method-2", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "Genevestigator software and the GEO2R tool", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "DEGs between SARS-CoV-2 infected hiPSC-CMs and non-infected hiPSC-CMs were screened by using Genevestigator software (Hruz et al., 2008) and the GEO2R tool (Barrett et al., 2013). p-Value <0.05 and a |log2FC| ≥ 0.5 were defined as the cut-off criteria."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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