Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enriched in astrocytes (239 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 3 Parkinson's papers of 144 | 0.82 |
| pathways Reactome | 13 pathways; mostly protein handling | 0.90 |
Knock down and overexpress NCAN in astrocytes; measure proteasome activity and the load of ubiquitinated protein and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- 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 degradation, and dopamine neuron survival in co-culture
- 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 NCAN in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- NCAN in astrocytes, braak+0.02 (p 0.965) → -0.61 (p 0.078)receipt 10285
- NCAN in dopamine neurons, braak-0.41 (p 0.273) → +0.26 (p 0.493)receipt 10286
Swarm cases
receipt 10286: NCAN in dopamine neurons, braak
- power
- full sample -0.15 (p 0.561, n 18), 95% CI -0.57 to +0.34. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.16 (p 0.538, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.16 (p 0.521, n 18). could be the mix.
- skeptic
- leave-one-out range -0.25 to -0.02, sign flips 0; without severely affected donors -0.15 (p 0.561, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NCAN in dopamine neurons.
case closed: nothing better to follow up.
receipt 10285: NCAN in astrocytes, braak
- power
- full sample -0.24 (p 0.332, n 18), 95% CI -0.64 to +0.25. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.22 (p 0.389, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.17 (p 0.504, n 18). could be the mix.
- skeptic
- leave-one-out range -0.39 to -0.15, sign flips 0; without severely affected donors -0.24 (p 0.332, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for NCAN in astrocytes.
case closed: nothing better to follow up.
Receipts
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