Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in pituicytes/fscs | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 124 | 0.91 |
| pathways Reactome | 16 pathways; mostly protein handling | 0.90 |
Knock down and overexpress GPC6 in oligodendrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves proteasome activity 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 GPC6 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- GPC6 in dopamine neurons, braak+0.45 (p 0.230) → +0.44 (p 0.235)receipt 8544
- GPC6 in oligodendrocytes, braak+0.05 (p 0.894) → -0.03 (p 0.946)receipt 8543
Swarm cases
receipt 8544: GPC6 in dopamine neurons, braak
- power
- full sample +0.45 (p 0.063, n 18), 95% CI -0.03 to +0.76. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.44 (p 0.066, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.39 (p 0.105, n 18). could be the mix.
- skeptic
- leave-one-out range +0.37 to +0.61, sign flips 0; without severely affected donors +0.45 (p 0.063, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GPC6 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8543: GPC6 in oligodendrocytes, braak
- power
- full sample -0.03 (p 0.915, n 18), 95% CI -0.49 to +0.45. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.01 (p 0.962, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.04 (p 0.867, n 18). could be the mix.
- skeptic
- leave-one-out range -0.15 to +0.10, sign flips 7; without severely affected donors -0.03 (p 0.915, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GPC6 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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