Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (628 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 37 | 0.91 |
| pathways Reactome | 56 pathways; mostly mitochondrial quality control | 1.00 |
Knock down and overexpress POLR2F in oligodendrocytes; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) by 20% or more against non-targeting and empty-vector controls, across three independent differentiations, the hypothesis is wrong.
- Lab request
- CRISPRi knockdown and lentiviral overexpression of POLR2F in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- POLR2F in dopamine neurons, braak-0.33 (p 0.389) → -0.38 (p 0.315)receipt 14134
- POLR2F in oligodendrocytes, braak-0.16 (p 0.687) → -0.65 (p 0.058)receipt 14133
Swarm cases
receipt 14134: POLR2F in dopamine neurons, braak
- power
- full sample -0.31 (p 0.211, n 18), 95% CI -0.68 to +0.18. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.28 (p 0.261, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.39 (p 0.111, n 18). could be the mix.
- skeptic
- leave-one-out range -0.40 to -0.22, sign flips 0; without severely affected donors -0.31 (p 0.211, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for POLR2F in dopamine neurons.
case closed: nothing better to follow up.
receipt 14133: POLR2F in oligodendrocytes, braak
- power
- full sample -0.38 (p 0.125, n 18), 95% CI -0.72 to +0.11. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.45 (p 0.063, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.54 (p 0.019, n 18). not the mix.
- skeptic
- leave-one-out range -0.51 to -0.30, sign flips 0; without severely affected donors -0.38 (p 0.125, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for POLR2F in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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