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, including oligodendrocytes; strongest in myonuclei | 0.75 |
| chemistry Open Targets | compounds already reach it: ucn-01, midostaurin, gsk-690693 +2 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 170 | 0.85 |
| pathways Reactome | 9 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress PRKCQ 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 PRKCQ 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
- PRKCQ in dopamine neurons, braak-0.25 (p 0.514) → -0.24 (p 0.533)receipt 15553
- PRKCQ in oligodendrocytes, braak-0.64 (p 0.063) → +0.27 (p 0.485)receipt 15552
Swarm cases
receipt 15553: PRKCQ in dopamine neurons, braak
- power
- full sample -0.23 (p 0.365, n 18), 95% CI -0.63 to +0.27. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.19 (p 0.444, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.33 (p 0.185, n 18). could be the mix.
- skeptic
- leave-one-out range -0.36 to -0.14, sign flips 0; without severely affected donors -0.23 (p 0.365, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PRKCQ in dopamine neurons.
case closed: nothing better to follow up.
receipt 15552: PRKCQ in oligodendrocytes, braak
- power
- full sample -0.29 (p 0.246, n 18), 95% CI -0.67 to +0.21. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.25 (p 0.323, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.33 (p 0.185, n 18). could be the mix.
- skeptic
- leave-one-out range -0.42 to -0.19, sign flips 0; without severely affected donors -0.29 (p 0.246, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PRKCQ in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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