Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched in oligodendrocytes (124 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 2,086 | 0.85 |
| pathways Reactome | 21 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress RAD50 in oligodendrocytes; measure evoked dopamine release and dopamine transporter uptake 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
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves evoked dopamine release 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 RAD50 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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
- RAD50 in oligodendrocytes, braak-0.20 (p 0.597) → -0.16 (p 0.672)receipt 11544
- RAD50 in dopamine neurons, braak+0.12 (p 0.767) → -0.18 (p 0.648)receipt 11545
Swarm cases
receipt 11545: RAD50 in dopamine neurons, braak
- power
- full sample -0.00 (p 0.997, n 18), 95% CI -0.47 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.14 (p 0.591, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.11 (p 0.677, n 18). could be the mix.
- skeptic
- leave-one-out range -0.12 to +0.12, sign flips 10; without severely affected donors -0.00 (p 0.997, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RAD50 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11544: RAD50 in oligodendrocytes, braak
- power
- full sample -0.23 (p 0.365, n 18), 95% CI -0.63 to +0.27. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.23 (p 0.365, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.20 (p 0.424, n 18). could be the mix.
- skeptic
- leave-one-out range -0.40 to -0.13, sign flips 0; without severely affected donors -0.23 (p 0.365, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RAD50 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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