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 enhanced in oligodendrocyte progenitor cells (686 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 | 8 Parkinson's papers of 575 | 0.71 |
| pathways Reactome | 7 pathways; mostly dopamine synapse | 1.00 |
Knock down and overexpress CASK in oligodendrocytes; measure evoked dopamine release and dopamine transporter uptake 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
- evoked dopamine release and dopamine transporter uptake
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves evoked dopamine release 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 CASK in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: evoked dopamine release and dopamine transporter uptake; 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
- CASK in dopamine neurons, braak-0.03 (p 0.944) → +0.57 (p 0.109)receipt 8705
- CASK in oligodendrocytes, braak+0.11 (p 0.784) → -0.37 (p 0.324)receipt 8704
Swarm cases
receipt 8705: CASK in dopamine neurons, braak
- power
- full sample +0.11 (p 0.671, n 18), 95% CI -0.38 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.22 (p 0.384, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.16 (p 0.538, n 18). could be the mix.
- skeptic
- leave-one-out range -0.01 to +0.24, sign flips 1; without severely affected donors +0.11 (p 0.671, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CASK in dopamine neurons.
case closed: nothing better to follow up.
receipt 8704: CASK in oligodendrocytes, braak
- power
- full sample -0.09 (p 0.728, n 18), 95% CI -0.53 to +0.40. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.715, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.03 (p 0.901, n 18). could be the mix.
- skeptic
- leave-one-out range -0.25 to -0.01, sign flips 0; without severely affected donors -0.09 (p 0.728, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CASK in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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