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 oligodendrocytes (2308 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 | 1 Parkinson's papers of 98 | 0.91 |
| pathways Reactome | 4 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress PIP4K2A 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 PIP4K2A 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
- PIP4K2A in dopamine neurons, braak+0.21 (p 0.591) → +0.27 (p 0.487)receipt 12621
- PIP4K2A in oligodendrocytes, braak+0.11 (p 0.784) → -0.09 (p 0.825)receipt 12620
Swarm cases
receipt 12621: PIP4K2A in dopamine neurons, braak
- power
- full sample +0.20 (p 0.429, n 18), 95% CI -0.30 to +0.61. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.429, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.38 (p 0.123, n 18). could be the mix.
- skeptic
- leave-one-out range +0.09 to +0.29, sign flips 0; without severely affected donors +0.20 (p 0.429, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PIP4K2A in dopamine neurons.
case closed: nothing better to follow up.
receipt 12620: PIP4K2A in oligodendrocytes, braak
- power
- full sample +0.08 (p 0.748, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.06 (p 0.827, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.04 (p 0.888, n 18). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.21, sign flips 2; without severely affected donors +0.08 (p 0.748, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PIP4K2A in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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