Analysis Proposal
Analysis Question
Can we validate the co-discussion relationship between APOE and TFR1 in neurodegeneration?
Datasets
Human Brain Transcriptome (HBT) RNA‑seq datasetGene Expression Omnibus (GEO) neurodegenerative disease cohorts (e.g., GSE125672, GSE48350)Alzheimer’s disease GWAS summary statistics (e.g., Kunkle et al. 2019)PubMed abstract corpus (2010‑2024) for text‑mining co‑mention analysis
Methods
Text‑mining co‑mention frequency analysis to compute odds ratio and significance of APOE–TFR1 co‑occurrence against a random background modelBrain‑tissue co‑expression analysis (Pearson/Spearman) across neurodegenerative datasets with false‑discovery rate correctionMendelian randomization / colocalization using AD GWAS and eQTL data to test for shared genetic effects on APOE and TFR1Knowledge‑graph embedding based link‑prediction to generate a confidence score for the APOE–TFR1 edge
Expected Outputs
- Significant co‑mention signal (odds ratio > 2, p < 0.05) supporting textual association
- Positive brain expression correlation (r > 0.3, q < 0.05) indicating co‑regulation
- No strong colocalization (posterior probability < 0.5) suggesting independent genetic contributions
- Updated edge trust score integrating textual, expression, and genetic evidence (e.g., trust > 0.7 would corroborate the relationship)