Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.31 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched, including oligodendrocytes; strongest in late spermatids | 0.75 |
| 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 1 pathway; mostly energy | 0.60 |
Knock down and overexpress SCLY in oligodendrocytes; measure oxygen consumption rate and ATP output 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
- oxygen consumption rate and ATP output
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves oxygen consumption rate 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 SCLY in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: oxygen consumption rate and ATP output; 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
- SCLY in dopamine neurons, braak-0.12 (p 0.749) → -0.52 (p 0.148)receipt 1167
- SCLY in oligodendrocytes, braak-0.57 (p 0.109) → +0.76 (p 0.017)receipt 1166
Swarm cases
receipt 1167: SCLY in dopamine neurons, braak
- power
- full sample -0.35 (p 0.150, n 18), 95% CI -0.70 to +0.14. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.37 (p 0.130, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.25 (p 0.310, n 18). could be the mix.
- skeptic
- leave-one-out range -0.53 to -0.27, sign flips 0; without severely affected donors -0.35 (p 0.150, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SCLY in dopamine neurons.
case closed: nothing better to follow up.
receipt 1166: SCLY in oligodendrocytes, braak
- power
- full sample -0.05 (p 0.847, n 18), 95% CI -0.50 to +0.43. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.05 (p 0.847, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.05 (p 0.847, n 18). could be the mix.
- skeptic
- leave-one-out range -0.17 to +0.06, sign flips 4; without severely affected donors -0.05 (p 0.847, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SCLY in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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