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 enhanced, including astrocytes; strongest in platelets | 0.75 |
| chemistry Open Targets | compounds already reach it: diquafosol, diquafosol tetrasodium | 0.90 |
| 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 | 3 pathways; mostly other | 0.30 |
Knock down and overexpress P2RY1 in astrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and degradation, and dopamine neuron survival in co-culture
- Rule-out
- If neither arm moves a transcriptome-wide state shift (bulk RNA-seq) 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 P2RY1 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- P2RY1 in dopamine neurons, braak-0.26 (p 0.498) → -0.05 (p 0.893)receipt 11436
- P2RY1 in astrocytes, braak+0.05 (p 0.894) → -0.30 (p 0.441)receipt 11435
Swarm cases
receipt 11436: P2RY1 in dopamine neurons, braak
- power
- full sample -0.07 (p 0.794, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.06 (p 0.827, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.12 (p 0.633, n 18). could be the mix.
- skeptic
- leave-one-out range -0.19 to +0.05, sign flips 4; without severely affected donors -0.07 (p 0.794, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for P2RY1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11435: P2RY1 in astrocytes, braak
- power
- full sample -0.10 (p 0.696, n 18), 95% CI -0.54 to +0.39. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.715, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.01 (p 0.969, n 18). could be the mix.
- skeptic
- leave-one-out range -0.26 to +0.03, sign flips 1; without severely affected donors -0.10 (p 0.696, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for P2RY1 in astrocytes.
case closed: nothing better to follow up.
Receipts
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