Comparative Transcriptomic Analysis of Neurodegeneration and Viral Infection: A Multi-Method Validation Framework

Abstract

AbstractParkinson's disease and influenza virus infection present with entirely different clinical pictures, yet both have been linked to shared inflammatory and neuroimmune mechanisms, an interest dating back to post-encephalitic parkinsonism following the 1918 influenza pandemic and supported by a 2026 meta-analysis reporting nearly double the odds of Parkinson's disease following prior influenza infection. This study compares gene expression profiles from two publicly available NCBI Gene Expression Omnibus DataSets, GDS5646 (Parkinson's disease, 10 samples) and GDS6063 (influenza infection, 10 samples), using joint cross-platform normalization, differential expression testing, correlation analysis, and functional enrichment to characterize shared and condition-specific transcriptomic signatures. After standardizing gene symbols, 12,579 genes were identified in common between the two conditions (significantly more than expected by chance; Fisher's exact and chi-square tests, both p < 0.001), while 8,183 genes were unique to the influenza dataset. Pearson correlation of shared-gene expression was low (r = 0.009), indicating no coordinated expression relationship despite the substantial overlap. A per-gene differential expression analysis (Welch's t-test with Benjamini-Hochberg FDR correction) identified genes significantly distinguishing the two conditions, including several with established roles in antiviral and immune signaling (RNF125, CD52, HCST, ITPKB). Gene Ontology enrichment of the shared gene set was dominated by broad regulatory terms, while genes unique to the influenza dataset were enriched for system process and G protein-coupled receptor signaling terms. KEGG pathway mapping of a subset of shared genes identified MAPK, Ras, and ErbB signaling pathways. Together, these convergent results point to overlapping immune and signaling machinery between neurodegenerative and viral-infection transcriptomes, consistent with known intersections between antiviral innate immune pathways and Parkinson's disease risk genes, and identify specific candidate genes meriting targeted follow-up rather than evidence of a shared coordinated transcriptional response. Keywords: transcriptomics, gene expression, Parkinson's disease, influenza, Gene Expression Omnibus, Gene Ontology enrichment, KEGG pathway analysis, neurodegeneration