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 enriched in oligodendrocytes (553 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: azd-5438, at-7519, roniciclib +1 | 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 | in no curated pathway | 0.00 |
Knock down and overexpress CDK18 in oligodendrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) 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
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- 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 CDK18 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); 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
- CDK18 in dopamine neurons, braak+0.10 (p 0.802) → -0.20 (p 0.615)receipt 11154
- CDK18 in oligodendrocytes, braak-0.44 (p 0.232) → +0.25 (p 0.517)receipt 11153
Swarm cases
receipt 11154: CDK18 in dopamine neurons, braak
- power
- full sample +0.01 (p 0.976, n 18), 95% CI -0.46 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.01 (p 0.976, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.02 (p 0.935, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.10, sign flips 6; without severely affected donors +0.01 (p 0.976, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CDK18 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11153: CDK18 in oligodendrocytes, braak
- power
- full sample -0.17 (p 0.493, n 18), 95% CI -0.59 to +0.32. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.08 (p 0.754, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.02 (p 0.949, n 18). could be the mix.
- skeptic
- leave-one-out range -0.29 to -0.07, sign flips 0; without severely affected donors -0.17 (p 0.493, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CDK18 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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