Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.06 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (350 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: jnj-54175446, azd9056, ce-224535 +2 | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 9 Parkinson's papers of 605 | 0.70 |
| pathways Reactome | 5 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress P2RX7 in oligodendrocytes; measure IL-1β and TNF release and surface HLA-DR 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; existing compounds already reach the inhibition arm.
- Molecular readout
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves IL-1β 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 P2RX7 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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
- P2RX7 in dopamine neurons, braak+0.17 (p 0.663) → +0.15 (p 0.699)receipt 4449
- P2RX7 in oligodendrocytes, braak+0.50 (p 0.175) → +0.42 (p 0.262)receipt 4448
Swarm cases
receipt 4449: P2RX7 in dopamine neurons, braak
- power
- full sample +0.18 (p 0.476, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.18 (p 0.476, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.18 (p 0.487, n 18). could be the mix.
- skeptic
- leave-one-out range +0.11 to +0.35, sign flips 0; without severely affected donors +0.18 (p 0.476, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for P2RX7 in dopamine neurons.
case closed: nothing better to follow up.
receipt 4448: P2RX7 in oligodendrocytes, braak
- power
- full sample +0.47 (p 0.047, n 18), 95% CI +0.01 to +0.77. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.44 (p 0.067, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.43 (p 0.077, n 18). could be the mix.
- skeptic
- leave-one-out range +0.39 to +0.60, sign flips 0; without severely affected donors +0.47 (p 0.047, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for P2RX7 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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