Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.07 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (851 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 1 pathway; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress UGT8 in oligodendrocytes; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux 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
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 UGT8 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; 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
- UGT8 in dopamine neurons, braak-0.43 (p 0.250) → +0.58 (p 0.102)receipt 3810
- UGT8 in oligodendrocytes, braak+0.24 (p 0.539) → +0.16 (p 0.685)receipt 3809
Swarm cases
receipt 3810: UGT8 in dopamine neurons, braak
- power
- full sample +0.02 (p 0.928, n 18), 95% CI -0.45 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.00 (p 0.997, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.08 (p 0.761, n 18). could be the mix.
- skeptic
- leave-one-out range -0.10 to +0.15, sign flips 8; without severely affected donors +0.02 (p 0.928, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for UGT8 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3809: UGT8 in oligodendrocytes, braak
- power
- full sample +0.14 (p 0.579, n 18), 95% CI -0.35 to +0.57. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.19 (p 0.450, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.17 (p 0.504, n 18). could be the mix.
- skeptic
- leave-one-out range +0.02 to +0.28, sign flips 0; without severely affected donors +0.14 (p 0.579, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for UGT8 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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