Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enriched in oligodendrocyte progenitor cells (85 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 129 | 0.91 |
| pathways Reactome | 2 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress NEU4 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 NEU4 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
- NEU4 in oligodendrocytes, braak+0.02 (p 0.964) → -0.15 (p 0.705)receipt 12147
- NEU4 in dopamine neurons, braak-0.66 (p 0.054) → -0.18 (p 0.646)receipt 12148
Swarm cases
receipt 12148: NEU4 in dopamine neurons, braak
- power
- full sample -0.41 (p 0.087, n 18), 95% CI -0.74 to +0.07. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.45 (p 0.060, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.51 (p 0.029, n 18). not the mix.
- skeptic
- leave-one-out range -0.53 to -0.33, sign flips 0; without severely affected donors -0.41 (p 0.087, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NEU4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 12147: NEU4 in oligodendrocytes, braak
- power
- full sample -0.08 (p 0.767, 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 0.767, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.03 (p 0.922, n 18). could be the mix.
- skeptic
- leave-one-out range -0.19 to +0.06, sign flips 2; without severely affected donors -0.08 (p 0.767, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NEU4 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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