Analysis of gene expression profiles and protein-protein interaction networks in multiple tissues of systemic sclerosis.
Common pathway
Functional analysis
Integrative gene expression analysis
Systemic sclerosis
Journal
BMC medical genomics
ISSN: 1755-8794
Titre abrégé: BMC Med Genomics
Pays: England
ID NLM: 101319628
Informations de publication
Date de publication:
27 12 2019
27 12 2019
Historique:
received:
21
02
2019
accepted:
19
11
2019
entrez:
29
12
2019
pubmed:
29
12
2019
medline:
20
5
2020
Statut:
epublish
Résumé
Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients. An integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein-protein interaction (PPI) networks. Then, functional clusters in PPI networks were determined. Enrichr, a gene list enrichment analysis tool, was utilized for the functional enrichment of clusters. A total of 12, 2, and 4 functional clusters from 619, 52, and 119 DEGs were determined in the lung, peripheral blood mononuclear cell (PBMC), and skin tissues, respectively. Analysis revealed that the tumor necrosis factor (TNF) signaling pathway was enriched significantly in the three investigated tissues as a common pathway. In addition, clusters associated with inflammation and immunity were common in the three investigated tissues. However, clusters related to the fibrosis process were common in lung and skin tissues. Analysis indicated that there were common pathological clusters that contributed to the pathogenesis of SSc in different tissues. Moreover, it seems that the common pathways in distinct tissues stem from a diverse set of genes.
Sections du résumé
BACKGROUND
Systemic sclerosis (SSc), a multi-organ disorder, is characterized by vascular abnormalities, dysregulation of the immune system, and fibrosis. The mechanisms underlying tissue pathology in SSc have not been entirely understood. This study intended to investigate the common and tissue-specific pathways involved in different tissues of SSc patients.
METHODS
An integrative gene expression analysis of ten independent microarray datasets of three tissues was conducted to identify differentially expressed genes (DEGs). DEGs were mapped to the search tool for retrieval of interacting genes (STRING) to acquire protein-protein interaction (PPI) networks. Then, functional clusters in PPI networks were determined. Enrichr, a gene list enrichment analysis tool, was utilized for the functional enrichment of clusters.
RESULTS
A total of 12, 2, and 4 functional clusters from 619, 52, and 119 DEGs were determined in the lung, peripheral blood mononuclear cell (PBMC), and skin tissues, respectively. Analysis revealed that the tumor necrosis factor (TNF) signaling pathway was enriched significantly in the three investigated tissues as a common pathway. In addition, clusters associated with inflammation and immunity were common in the three investigated tissues. However, clusters related to the fibrosis process were common in lung and skin tissues.
CONCLUSIONS
Analysis indicated that there were common pathological clusters that contributed to the pathogenesis of SSc in different tissues. Moreover, it seems that the common pathways in distinct tissues stem from a diverse set of genes.
Identifiants
pubmed: 31881890
doi: 10.1186/s12920-019-0632-2
pii: 10.1186/s12920-019-0632-2
pmc: PMC6935135
doi:
Substances chimiques
Tumor Necrosis Factor-alpha
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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