Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (2128 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 | 3 Parkinson's papers of 268 | 0.82 |
| pathways Reactome | 1 pathway; mostly growth signalling | 0.60 |
Knock down and overexpress PHLPP1 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 PHLPP1 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
- PHLPP1 in oligodendrocytes, braak+0.06 (p 0.873) → +0.10 (p 0.803)receipt 3588
- PHLPP1 in dopamine neurons, braak+0.03 (p 0.946) → +0.28 (p 0.470)receipt 3589
Swarm cases
receipt 3589: PHLPP1 in dopamine neurons, braak
- power
- full sample +0.16 (p 0.521, n 18), 95% CI -0.33 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.18 (p 0.482, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.28 (p 0.254, n 18). could be the mix.
- skeptic
- leave-one-out range +0.05 to +0.27, sign flips 0; without severely affected donors +0.16 (p 0.521, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PHLPP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3588: PHLPP1 in oligodendrocytes, braak
- power
- full sample +0.14 (p 0.573, n 18), 95% CI -0.35 to +0.57. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.19 (p 0.455, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.10 (p 0.702, n 18). could be the mix.
- skeptic
- leave-one-out range +0.03 to +0.25, sign flips 0; without severely affected donors +0.14 (p 0.573, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PHLPP1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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