Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.18 (overall 0.11) | 0.18 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in neutrophils | 0.75 |
| 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 | 4 pathways; mostly other | 0.30 |
Knock down and overexpress ARHGEF2 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.
- 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 ARHGEF2 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
- ARHGEF2 in dopamine neurons, braak-0.06 (p 0.877) → -0.54 (p 0.130)receipt 2458
- ARHGEF2 in oligodendrocytes, braak-0.39 (p 0.297) → -0.36 (p 0.344)receipt 2457
Swarm cases
receipt 2458: ARHGEF2 in dopamine neurons, braak
- power
- full sample -0.31 (p 0.214, n 18), 95% CI -0.68 to +0.19. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.31 (p 0.214, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.31 (p 0.207, n 18). could be the mix.
- skeptic
- leave-one-out range -0.46 to -0.22, sign flips 0; without severely affected donors -0.31 (p 0.214, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ARHGEF2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 2457: ARHGEF2 in oligodendrocytes, braak
- power
- full sample -0.22 (p 0.374, n 18), 95% CI -0.62 to +0.27. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.22 (p 0.374, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.26 (p 0.289, n 18). could be the mix.
- skeptic
- leave-one-out range -0.34 to -0.14, sign flips 0; without severely affected donors -0.22 (p 0.374, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ARHGEF2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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