Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.71 (overall 0.45) | 0.71 |
| 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 | 54 Parkinson's papers of 75 | 0.47 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress RAB29 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 RAB29 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
- RAB29 in dopamine neurons, braak-0.50 (p 0.168) → +0.21 (p 0.583)receipt 0414
In the sealed studies
- The lysosomal axis in dopamine neurons: did not hold
Swarm cases
receipt 0414: RAB29 in dopamine neurons, braak
- power
- full sample -0.30 (p 0.232, n 18), 95% CI -0.67 to +0.20. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.30 (p 0.232, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.30 (p 0.232, n 18). could be the mix.
- skeptic
- leave-one-out range -0.40 to -0.19, sign flips 0; without severely affected donors -0.30 (p 0.232, n 18). fragile.
- cell type
- strongest in OPCs: -0.62 (p 0.0062, n 18) vs -0.30 in dopamine neurons. proposing OPCs.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RAB29 in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up RAB29 · OPCs · braak: substantia nigra, an independent cohort (Parkinson's or LBD vs controls) -0.28 p 0.328 (needs p < 0.0018)
Receipts
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