Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.03 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in vascular smooth muscle cells | 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 383 | 0.91 |
| pathways Reactome | 11 pathways; mostly protein handling | 0.90 |
Knock down and overexpress CSPG4 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 CSPG4 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
- CSPG4 in dopamine neurons, braak-0.09 (p 0.825) → -0.61 (p 0.084)receipt 6730
- CSPG4 in oligodendrocytes, braak-0.63 (p 0.068) → -0.48 (p 0.195)receipt 6729
Swarm cases
receipt 6730: CSPG4 in dopamine neurons, braak
- power
- full sample -0.30 (p 0.232, n 18), 95% CI -0.67 to +0.20. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.28 (p 0.258, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.30 (p 0.232, n 18). could be the mix.
- skeptic
- leave-one-out range -0.39 to -0.20, sign flips 0; without severely affected donors -0.30 (p 0.232, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CSPG4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6729: CSPG4 in oligodendrocytes, braak
- power
- full sample -0.48 (p 0.045, n 18), 95% CI -0.77 to -0.01. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.48 (p 0.045, n 18). holds up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.52 (p 0.027, n 18). not the mix.
- skeptic
- leave-one-out range -0.63 to -0.40, sign flips 0; without severely affected donors -0.48 (p 0.045, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CSPG4 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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