Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.23 (overall 0.15) | 0.23 |
| cell type Human Protein Atlas | cell type enhanced in astrocytes (289 nCPM) | 1.00 |
| chemistry Open Targets | compounds already reach it: unasnemab, elezanumab | 0.81 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 7 Parkinson's papers of 260 | 0.73 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress RGMA in astrocytes; measure a transcriptome-wide state shift (bulk RNA-seq) and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- 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 degradation, and dopamine neuron survival in co-culture
- 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 RGMA in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: a transcriptome-wide state shift (bulk RNA-seq); α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- RGMA in dopamine neurons, braak-0.14 (p 0.720) → -0.45 (p 0.222)receipt 2207
- RGMA in astrocytes, braak+0.05 (p 0.893) → +0.27 (p 0.478)receipt 2206
Swarm cases
receipt 2207: RGMA in dopamine neurons, braak
- power
- full sample -0.34 (p 0.164, n 18), 95% CI -0.70 to +0.15. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.42 (p 0.086, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.47 (p 0.050, n 18). not the mix.
- skeptic
- leave-one-out range -0.47 to -0.25, sign flips 0; without severely affected donors -0.34 (p 0.164, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RGMA in dopamine neurons.
case closed: nothing better to follow up.
receipt 2206: RGMA in astrocytes, braak
- power
- full sample +0.13 (p 0.615, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.12 (p 0.627, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.05 (p 0.854, n 18). could be the mix.
- skeptic
- leave-one-out range -0.01 to +0.24, sign flips 1; without severely affected donors +0.13 (p 0.615, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RGMA in astrocytes.
case closed: nothing better to follow up.
Receipts
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