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 microglia; strongest in syncytiotrophoblasts | 0.75 |
| chemistry Open Targets | compounds already reach it: diquafosol tetrasodium, diquafosol | 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 | 2 pathways; mostly other | 0.30 |
Knock down and overexpress P2RY6 in microglia; measure a transcriptome-wide state shift (bulk RNA-seq) and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- 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 P2RY6 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- P2RY6 in microglia, braak-0.12 (p 0.760) → -0.66 (p 0.053)receipt 8120
- P2RY6 in dopamine neurons, braak-0.60 (p 0.089) → -0.50 (p 0.167)receipt 8121
Swarm cases
receipt 8121: P2RY6 in dopamine neurons, braak
- power
- full sample -0.51 (p 0.032, n 18), 95% CI -0.79 to -0.05. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.55 (p 0.018, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.67 (p 0.0023, n 18). not the mix.
- skeptic
- leave-one-out range -0.61 to -0.44, sign flips 0; without severely affected donors -0.51 (p 0.032, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for P2RY6 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8120: P2RY6 in microglia, braak
- power
- full sample -0.40 (p 0.099, n 18), 95% CI -0.73 to +0.08. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.34 (p 0.164, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.34 (p 0.161, n 18). could be the mix.
- skeptic
- leave-one-out range -0.53 to -0.31, sign flips 0; without severely affected donors -0.40 (p 0.099, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for P2RY6 in microglia.
case closed: nothing better to follow up.
Receipts
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