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 nk-cells | 0.75 |
| chemistry Open Targets | compounds already reach it: fingolimod hydrochloride, etrasimod, ozanimod +5 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 166 | 0.85 |
| pathways Reactome | 2 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress S1PR5 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 S1PR5 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
- S1PR5 in dopamine neurons, braak-0.32 (p 0.400) → +0.08 (p 0.838)receipt 16099
- S1PR5 in oligodendrocytes, braak-0.39 (p 0.297) → -0.23 (p 0.560)receipt 16098
Swarm cases
receipt 16099: S1PR5 in dopamine neurons, braak
- power
- full sample -0.11 (p 0.664, n 18), 95% CI -0.55 to +0.38. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.722, 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 0.658, n 18). could be the mix.
- skeptic
- leave-one-out range -0.25 to -0.02, sign flips 0; without severely affected donors -0.11 (p 0.664, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for S1PR5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 16098: S1PR5 in oligodendrocytes, braak
- power
- full sample -0.20 (p 0.434, n 18), 95% CI -0.61 to +0.30. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.25 (p 0.323, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.32 (p 0.191, n 18). could be the mix.
- skeptic
- leave-one-out range -0.31 to -0.10, sign flips 0; without severely affected donors -0.20 (p 0.434, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for S1PR5 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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