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 in oligodendrocyte progenitor cells (760 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 215 | 0.85 |
| pathways Reactome | 22 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress KAT2B 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 KAT2B 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
- KAT2B in dopamine neurons, braak-0.21 (p 0.581) → -0.07 (p 0.859)receipt 12323
- KAT2B in oligodendrocytes, braak-0.52 (p 0.150) → +0.05 (p 0.893)receipt 12322
Swarm cases
receipt 12323: KAT2B in dopamine neurons, braak
- power
- full sample -0.05 (p 0.847, n 18), 95% CI -0.50 to +0.43. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.11 (p 0.658, 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 0.652, n 18). could be the mix.
- skeptic
- leave-one-out range -0.19 to +0.08, sign flips 4; without severely affected donors -0.05 (p 0.847, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KAT2B in dopamine neurons.
case closed: nothing better to follow up.
receipt 12322: KAT2B in oligodendrocytes, braak
- power
- full sample -0.12 (p 0.646, n 18), 95% CI -0.55 to +0.37. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.521, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.03 (p 0.894, n 18). could be the mix.
- skeptic
- leave-one-out range -0.26 to -0.02, sign flips 0; without severely affected donors -0.12 (p 0.646, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KAT2B in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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