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, including oligodendrocytes; strongest in cardiomyocytes | 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 | 4 Parkinson's papers of 262 | 0.79 |
| pathways Reactome | 2 pathways; mostly protein handling | 0.90 |
Knock down and overexpress DDO in oligodendrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves proteasome activity 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 DDO in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- DDO in dopamine neurons, braak+0.18 (p 0.635) → -0.32 (p 0.407)receipt 12939
- DDO in oligodendrocytes, braak-0.11 (p 0.784) → +0.13 (p 0.739)receipt 12938
Swarm cases
receipt 12939: DDO in dopamine neurons, braak
- power
- full sample -0.07 (p 0.781, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.08 (p 0.754, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.10 (p 0.696, n 18). could be the mix.
- skeptic
- leave-one-out range -0.23 to +0.06, sign flips 2; without severely affected donors -0.07 (p 0.781, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DDO in dopamine neurons.
case closed: nothing better to follow up.
receipt 12938: DDO in oligodendrocytes, braak
- power
- full sample -0.02 (p 0.949, n 18), 95% CI -0.48 to +0.45. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.834, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.07 (p 0.794, n 18). could be the mix.
- skeptic
- leave-one-out range -0.16 to +0.13, sign flips 7; without severely affected donors -0.02 (p 0.949, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for DDO in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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