Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.52 (overall 0.38) | 0.52 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (391 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 | 2 Parkinson's papers of 100 | 0.85 |
| pathways Reactome | 1 pathway; mostly growth signalling | 0.60 |
Knock down and overexpress TNK2 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.
- 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 TNK2 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
- TNK2 in oligodendrocytes, braak+0.09 (p 0.820) → -0.63 (p 0.067)receipt 0691
- TNK2 in dopamine neurons, braak-0.16 (p 0.672) → -0.55 (p 0.122)receipt 0692
Swarm cases
receipt 0692: TNK2 in dopamine neurons, braak
- power
- full sample -0.47 (p 0.049, n 18), 95% CI -0.77 to -0.01. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.49 (p 0.038, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.59 (p 0.0096, n 18). not the mix.
- skeptic
- leave-one-out range -0.61 to -0.40, sign flips 0; without severely affected donors -0.47 (p 0.049, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNK2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0691: TNK2 in oligodendrocytes, braak
- power
- full sample -0.31 (p 0.207, n 18), 95% CI -0.68 to +0.18. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.30 (p 0.228, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.25 (p 0.323, n 18). could be the mix.
- skeptic
- leave-one-out range -0.49 to -0.22, sign flips 0; without severely affected donors -0.31 (p 0.207, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNK2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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