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Peer-reviewedCC BY-NC 4.0Bioinformatics and Biology Insights

Identification of Key Genes and Pathways in Parkinson’s Disease Through Bioinformatics Analysis

  • Ehsan Lotfi1,2
  • Arsh Haj Mohamad Ebrahim Ketabforoush1
  • Fereshteh Azeditehrani1
  • Nooshin Ahmadirad1
  • Narges Daneshafrooz3
  • Fereshteh Golab1
  1. 1Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
  2. 2Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences, Tehran, Iran
  3. 3School of Rehabilitation Science, Iran University of Medical Sciences, Tehran, Iran
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Abstract

Parkinson’s disease (PD), the second most common neurodegenerative disorder, involves nigral dopaminergic neuron loss. Integrative transcriptomics of central and peripheral tissues may uncover conserved molecular signatures, biomarkers, and therapeutic targets. Gene expression datasets from substantia nigra (GSE8397) and peripheral blood mononuclear cells (GSE22491) were retrieved from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using GEO2R with an adjusted P < 0.05 and |log2 fold change| ≥1. Shared DEGs underwent Gene Ontology, KEGG, and Reactome enrichment analyses. Protein–protein interaction networks were constructed using STRING and Cytoscape, followed by hub gene identification through multiple topological algorithms. Cell-type composition was estimated with xCell, and therapeutic relevance was evaluated with DGIdb and the Open Targets Platform. We identified 18 common DEGs (14 concordant, 4 discordant), enriched in dopaminergic/synaptic pathways. Five hub genes (SNCA, TH, DDC, SLC18A2, COMT) were consistently identified. Cell deconvolution revealed neuronal loss and oligodendrocyte increase. Drug analysis confirmed approved therapeutics and clinical relevance, including SNCA-targeted agents. Integrative transcriptomics identified conserved central-peripheral signatures in PD. These hub genes are candidate biomarkers/therapeutic targets, offering a systems-level framework for disease mechanisms and independent cohort validation.

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Cite

BibTeXRIS
BibTeX
@article{lotfi2026identification,
  title = {{Identification of Key Genes and Pathways in Parkinson’s Disease Through Bioinformatics Analysis}},
  author = {Ehsan Lotfi and Arsh Haj Mohamad Ebrahim Ketabforoush and Fereshteh Azeditehrani and Nooshin Ahmadirad and Narges Daneshafrooz and Fereshteh Golab},
  journal = {Bioinformatics and Biology Insights},
  year = {2026},
  month = sep,
  doi = {10.1177/11779322261489966},
  url = {https://doi.org/10.1177/11779322261489966},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Identification of Key Genes and Pathways in Parkinson’s Disease Through Bioinformatics Analysis
AU  - Ehsan Lotfi
AU  - Arsh Haj Mohamad Ebrahim Ketabforoush
AU  - Fereshteh Azeditehrani
AU  - Nooshin Ahmadirad
AU  - Narges Daneshafrooz
AU  - Fereshteh Golab
PY  - 2026
DA  - 2026/09/16
JO  - Bioinformatics and Biology Insights
DO  - 10.1177/11779322261489966
UR  - https://doi.org/10.1177/11779322261489966
AB  - Parkinson’s disease (PD), the second most common neurodegenerative disorder, involves nigral dopaminergic neuron loss. Integrative transcriptomics of central and peripheral tissues may uncover conserved molecular signatures, biomarkers, and therapeutic targets. Gene expression datasets from substantia nigra (GSE8397) and peripheral blood mononuclear cells (GSE22491) were retrieved from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified using GEO2R with an adjusted P < 0.05 and |log2 fold change| ≥1. Shared DEGs underwent Gene Ontology, KEGG, and Reactome enrichment analyses. Protein–protein interaction networks were constructed using STRING and Cytoscape, followed by hub gene identification through multiple topological algorithms. Cell-type composition was estimated with xCell, and therapeutic relevance was evaluated with DGIdb and the Open Targets Platform. We identified 18 common DEGs (14 concordant, 4 discordant), enriched in dopaminergic/synaptic pathways. Five hub genes (SNCA, TH, DDC, SLC18A2, COMT) were consistently identified. Cell deconvolution revealed neuronal loss and oligodendrocyte increase. Drug analysis confirmed approved therapeutics and clinical relevance, including SNCA-targeted agents. Integrative transcriptomics identified conserved central-peripheral signatures in PD. These hub genes are candidate biomarkers/therapeutic targets, offering a systems-level framework for disease mechanisms and independent cohort validation.
SN  - 1177-9322
ER  -