Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.58 (overall 0.35) | 0.58 |
| cell type Human Protein Atlas | cell type enhanced outside the brain (mast cells) | 0.10 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 152 | 0.91 |
| pathways Reactome | 2 pathways; mostly other | 0.30 |
Knock down and overexpress GPR65 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 GPR65 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
- GPR65 in dopamine neurons, braak+0.75 (p 0.019) → +0.16 (p 0.680)receipt 0874
Swarm cases
receipt 0874: GPR65 in dopamine neurons, braak
- power
- full sample +0.36 (p 0.145, n 18), 95% CI -0.13 to +0.71. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.44 (p 0.066, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.61 (p 0.0075, n 18). not the mix.
- skeptic
- leave-one-out range +0.28 to +0.53, sign flips 0; without severely affected donors +0.36 (p 0.145, n 18). fragile.
- cell type
- strongest in oligodendrocytes: -0.63 (p 0.0049, n 18) vs +0.36 in dopamine neurons. proposing oligodendrocytes.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GPR65 in dopamine neurons.
follow-up registered; not confirmed in substantia nigra, an independent cohort.
follow-up GPR65 · oligodendrocytes · braak: substantia nigra, an independent cohort: not measured
Receipts
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