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 oligodendrocytes (1292 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: gsk-2256098, cep-37440, pf-00562271 +4 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 891 | 0.82 |
| pathways Reactome | 17 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress PTK2 in oligodendrocytes; measure phospho-ERK and phospho-AKT response to GDNF 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; existing compounds already reach the inhibition arm.
- Molecular readout
- phospho-ERK and phospho-AKT response to GDNF
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves phospho-ERK 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 PTK2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: phospho-ERK and phospho-AKT response to GDNF; 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
- PTK2 in dopamine neurons, braak-0.11 (p 0.775) → +0.24 (p 0.539)receipt 11334
- PTK2 in oligodendrocytes, braak+0.20 (p 0.607) → -0.59 (p 0.096)receipt 11333
Swarm cases
receipt 11334: PTK2 in dopamine neurons, braak
- power
- full sample -0.01 (p 0.956, n 18), 95% CI -0.48 to +0.46. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.02 (p 0.942, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.14 (p 0.567, n 18). could be the mix.
- skeptic
- leave-one-out range -0.15 to +0.09, sign flips 6; without severely affected donors -0.01 (p 0.956, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PTK2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11333: PTK2 in oligodendrocytes, braak
- power
- full sample -0.24 (p 0.341, n 18), 95% CI -0.63 to +0.26. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.17 (p 0.498, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.11 (p 0.664, n 18). could be the mix.
- skeptic
- leave-one-out range -0.37 to -0.12, sign flips 0; without severely affected donors -0.24 (p 0.341, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PTK2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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