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 astrocytes (5171 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 17 pathways; mostly protein handling | 0.90 |
Knock down and overexpress GPC5 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 GPC5 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
- GPC5 in astrocytes, braak-0.01 (p 0.982) → +0.24 (p 0.537)receipt 12372
- GPC5 in dopamine neurons, braak+0.76 (p 0.019) → -0.05 (p 0.893)receipt 12373
Swarm cases
receipt 12373: GPC5 in dopamine neurons, braak
- power
- full sample +0.36 (p 0.137, n 18), 95% CI -0.12 to +0.71. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.36 (p 0.142, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.38 (p 0.116, n 18). could be the mix.
- skeptic
- leave-one-out range +0.31 to +0.56, sign flips 0; without severely affected donors +0.36 (p 0.137, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GPC5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 12372: GPC5 in astrocytes, braak
- power
- full sample +0.20 (p 0.424, n 18), 95% CI -0.29 to +0.61. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.18 (p 0.465, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.24 (p 0.337, n 18). could be the mix.
- skeptic
- leave-one-out range +0.11 to +0.33, sign flips 0; without severely affected donors +0.20 (p 0.424, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GPC5 in astrocytes.
case closed: nothing better to follow up.
Receipts
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