Integrated proteogenomic profiling reveals coordinated differential expression signatures during neuroinflammation.

Area of Science:

• Neuroscience
• Immunology
• Systems Biology

Background:

• Experimental autoimmune encephalomyelitis (EAE) is a crucial model for studying autoimmune neuroinflammation.
• A comprehensive understanding of the central nervous system's (CNS) transcriptional and proteomic changes in EAE has been lacking.

Purpose of the Study:

• To perform integrated proteogenomic profiling of the spinal cord in EAE mice.
• To characterize the molecular dysregulation during acute autoimmune neuroinflammation.

Main Methods:

• Deep proteogenomic profiling using RNA-sequencing (RNA-seq) and liquid chromatography-tandem mass spectrometry (LC-MS/MS).
• Analysis of spinal cord tissue from mice with induced EAE during the acute disease phase.
• Data deposited in Gene Expression Omnibus (GEO) and Proteomics Identifications (PRIDE) databases.

Main Results:

• Identified significant upregulation of immune response pathways and downregulation of neuronal, synaptic, and mitochondrial pathways.
• Demonstrated high concordance between transcriptomic and proteomic data (Rₚ = 0.867).
• Revealed that protein-level analysis is critical for detecting synaptic and metabolic deficits, which transcriptomics alone may underestimate. Immune cell infiltration and glial cell activation, rather than plasma leakage, drive most non-CNS protein changes.

Conclusions:

• The integrated dataset provides a multilayered view of molecular remodeling in neuroinflammation.
• Refined mechanistic understanding of biomarker origins in inflamed CNS tissue.
• Emphasized the importance of combined transcriptomic and proteomic approaches for studying complex diseases like EAE.