DNA Methylation Clock Drift at Glial Promoters
Curated pathway from expert analysis
flowchart TD
A["DNA Methylation Clock<br/>Hypothesis Target"]
B["Pathway Dysregulation<br/>Cited Mechanism"]
C["Cellular Response<br/>Stress or Clearance Change"]
D["Neural Circuit Effect<br/>Synapse/Glia Vulnerability"]
E["Neurodegeneration<br/>Disease-Relevant Outcome"]
A --> B
B --> C
C --> D
D --> E
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for DNA yet. Search RCSB →
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for DNA Methylation Clock.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF glial promoter methylation drift contributes to neurodegeneration, THEN CRISPR-Cas9 mediated repression of DNMT3A at candidate drifted glial promoters (via dCas9-DNMT3A targeting GFAP, ALDH1L1, OLI | ≥40% reduction in AT8+ cells and ≥25% improvement in Morris water maze performance | — no observation — | pending | 0.35 |
| IF DNA methylation clock drift selectively accelerates at glial promoters in neurodegeneration, THEN isolated astrocytes and oligodendrocytes from post-mortem prefrontal cortex of Alzheimer's disease | Glial epigenetic age acceleration >2.5 years in neurodegeneration cohort vs. control | — no observation — | pending | 0.55 |