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 (1231 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 722 | 0.85 |
| pathways Reactome | 25 pathways; mostly growth signalling | 0.60 |
Knock down and overexpress GAB1 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 GAB1 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
- GAB1 in dopamine neurons, braak+0.26 (p 0.502) → -0.06 (p 0.877)receipt 13283
- GAB1 in oligodendrocytes, braak-0.04 (p 0.911) → +0.20 (p 0.597)receipt 13282
Swarm cases
receipt 13283: GAB1 in dopamine neurons, braak
- power
- full sample +0.12 (p 0.640, n 18), 95% CI -0.37 to +0.55. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.13 (p 0.621, 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 +0.01 to +0.26, sign flips 0; without severely affected donors +0.12 (p 0.640, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GAB1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 13282: GAB1 in oligodendrocytes, 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
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.33 (p 0.176, n 18). could be the mix.
- skeptic
- leave-one-out range +0.09 to +0.32, 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 GAB1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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