Sex-specific and opposite modulatory aspects revealed by PPI network and pathway analysis of ischemic stroke in humans


Autoři: Yan Lv aff001;  XY He aff002;  Dongguo Li aff003;  Tao Liu aff002;  GQ Wen aff002;  Junfa Li aff001
Působiště autorů: Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China aff001;  Department of Neurology, Hainan General Hospital, Haikou, China aff002;  Department of Bioinformatics and Engineering, School of Basic Medical Sciences, Capital Medical University, Peking, China aff003
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pone.0227481

Souhrn

Background

Ischemic Stroke (IS) is a major disease which greatly threatens human health. Recent studies showed sex-specific outcomes and mechanisms of cerebral ischemic stroke. This study aimed to identify the key changes of gene expression between male and female IS in humans.

Methods

Gene expression dataset GSE22255, including peripheral blood samples, was downloaded from the Gene Expression Omnibus (GEO) dataset. Differentially Expressed Genes (DEGs) with a LogFC>1, and a P-value <0.05 were screened by BioConductor R package and grouped in female, male and overlap DEGs for further bioinformatic analysis. Gene Ontology (GO) functional annotation, Protein-Protein Interaction (PPI) network, “Molecular Complex Detection” (MCODE) modules, CytoNCA (cytoscape network centrality analysis) essential genes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway interrelation analysis were performed.

Results

In a total of 54,665 genes, 185 (73 ups and 112 downs) DEGs in the female dataset, 461 DEGs (297 ups and 164 downs) in the male dataset, within which 118 DEGs overlapped (7 similar changes in female and male, 111 opposite changes in female and male) were obtained from the GSE22255 dataset. Female, male and overlapping DEGs enriched for similar cellular components and molecular function. Male DEGs enriched for divergent biological processes from female and overlapping DEGs. Sex-specific and overlapping DEGs were put into the PPI network. Overlapping genes such as IL6, presented opposite changes and were mainly involved in cytokine-cytokine receptor interactions, the TNF-signalling pathway, etc.

Conclusion

The analysis of sex-specific DEGs from GEO human blood samples showed that not only specific but also opposite DEG alterations in the female and male stroke genome wide dataset. The results provided an overview of sex-specific mechanisms, which might provide insight into stroke and its biomarkers and lead to sex-specific prognosis and treatment strategies in future clinical practice.

Klíčová slova:

Apoptosis – Cell binding – Centrality – Cytokine receptors – Chemokines – Immune response – Network analysis – stroke – Stroke


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