Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.36 (overall 0.22) | 0.36 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| 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 | 3 pathways; mostly other | 0.30 |
Knock down and overexpress CDC42BPB in a dopamine neuron, astrocyte and microglia tri-culture; measure a transcriptome-wide state shift (bulk RNA-seq) and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- a transcriptome-wide state shift (bulk RNA-seq)
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- 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 CDC42BPB in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- CDC42BPB in dopamine neurons, braak-0.62 (p 0.073) → -0.11 (p 0.773)receipt 1905
Swarm cases
receipt 1905: CDC42BPB in dopamine neurons, braak
- power
- full sample -0.35 (p 0.160, n 18), 95% CI -0.70 to +0.14. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.35 (p 0.149, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.39 (p 0.107, n 18). could be the mix.
- skeptic
- leave-one-out range -0.48 to -0.26, sign flips 0; without severely affected donors -0.35 (p 0.160, n 18). fragile.
- cell type
- strongest in oligodendrocytes: -0.68 (p 0.0018, n 18) vs -0.35 in dopamine neurons. proposing oligodendrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CDC42BPB in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up CDC42BPB · oligodendrocytes · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) -0.22 p 0.424 (needs p < 8.2e-4)
Receipts
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