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 oligodendrocytes; strongest in rod photoreceptor cells | 0.75 |
| chemistry Open Targets | compounds already reach it: gsk-690693 | 0.80 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 201 | 0.85 |
| pathways Reactome | 27 pathways; mostly protein handling | 0.90 |
Knock down and overexpress PRKACB in oligodendrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 PRKACB in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- PRKACB in dopamine neurons, braak+0.38 (p 0.309) → +0.17 (p 0.665)receipt 7640
- PRKACB in oligodendrocytes, braak+0.43 (p 0.243) → -0.09 (p 0.815)receipt 7639
Swarm cases
receipt 7640: PRKACB in dopamine neurons, braak
- power
- full sample +0.27 (p 0.285, n 18), 95% CI -0.23 to +0.65. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.25 (p 0.315, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.45 (p 0.063, n 18). could be the mix.
- skeptic
- leave-one-out range +0.17 to +0.37, sign flips 0; without severely affected donors +0.27 (p 0.285, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PRKACB in dopamine neurons.
case closed: nothing better to follow up.
receipt 7639: PRKACB in oligodendrocytes, braak
- power
- full sample +0.13 (p 0.603, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.14 (p 0.591, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.07 (p 0.787, n 18). could be the mix.
- skeptic
- leave-one-out range +0.05 to +0.31, sign flips 0; without severely affected donors +0.13 (p 0.603, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PRKACB in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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