Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.55 (overall 0.33) | 0.55 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (11 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| 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 | in no curated pathway | 0.00 |
Knock down and overexpress GDF6 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 GDF6 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
- GDF6 in dopamine neurons, braak-0.64 (p 0.065) → -0.45 (p 0.227)receipt 1009
- GDF6 in oligodendrocytes, braak-0.29 (p 0.445) → +0.05 (p 0.907)receipt 1008
Swarm cases
receipt 1009: GDF6 in dopamine neurons, braak
- power
- full sample -0.25 (p 0.319, n 18), 95% CI -0.64 to +0.25. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.21 (p 0.408, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.40 (p 0.103, n 18). could be the mix.
- skeptic
- leave-one-out range -0.38 to -0.15, sign flips 0; without severely affected donors -0.25 (p 0.319, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GDF6 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1008: GDF6 in oligodendrocytes, braak
- power
- full sample -0.02 (p 0.935, n 18), 95% CI -0.48 to +0.45. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.928, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.27 (p 0.281, n 18). could be the mix.
- skeptic
- leave-one-out range -0.11 to +0.12, sign flips 6; without severely affected donors -0.02 (p 0.935, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for GDF6 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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