Cross-Omic Comparative Analysis Identifies Transcriptomic Signatures and Exploratory Gene Set-Level Signals in...

Area of Science:

• Neuroscience
• Genomics
• Epigenetics

Background:

• Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal neurodegenerative disorder with undefined pathogenesis.
• Public multi-omic datasets are valuable but limited by tissue and platform variability for comparative analysis.

Purpose of the Study:

• To perform a cross-omic comparative analysis of sCJD datasets across transcriptomic, post-transcriptional, and epigenomic layers.
• To identify reproducible molecular signals and patterns within and across different molecular data types.

Main Methods:

• Analysis of four sCJD case-control datasets (mRNA, miRNA, DNA methylation).
• Differential feature, overrepresentation, and gene set enrichment analyses within each layer.
• Cross-layer comparison at gene and Gene Ontology Biological Process (GO-BP) levels, evaluating reproducibility.

Main Results:

• Limited gene-level overlap observed across molecular layers, attributed to data heterogeneity.
• No significant cross-omic GO-BP gene set overlap under stringent FDR control.
• Exploratory analysis revealed nominal overlap in GO-BP terms related to cell-substrate adhesion between transcriptomic and DNA methylation data.

Conclusions:

• Cross-omic comparative analysis is a viable framework for hypothesis generation in rare neurodegenerative diseases like sCJD.
• Findings suggest potential roles for cell-substrate adhesion pathways in sCJD pathogenesis.
• Further research is needed to validate exploratory findings and refine multi-omic integration methods.