Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.41 (overall 0.25) | 0.41 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in pancreatic islet cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 114 | 0.91 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress PCDH17 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 PCDH17 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
- PCDH17 in oligodendrocytes, braak-0.68 (p 0.046) → -0.04 (p 0.925)receipt 1703
- PCDH17 in dopamine neurons, braak-0.02 (p 0.963) → +0.64 (p 0.064)receipt 1704
Swarm cases
receipt 1704: PCDH17 in dopamine neurons, braak
- power
- full sample +0.36 (p 0.142, n 18), 95% CI -0.13 to +0.71. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.40 (p 0.103, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.48 (p 0.044, n 18). not the mix.
- skeptic
- leave-one-out range +0.28 to +0.48, sign flips 0; without severely affected donors +0.36 (p 0.142, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PCDH17 in dopamine neurons.
case closed: nothing better to follow up.
receipt 1703: PCDH17 in oligodendrocytes, braak
- power
- full sample -0.32 (p 0.194, n 18), 95% CI -0.69 to +0.17. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.33 (p 0.182, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.26 (p 0.294, n 18). could be the mix.
- skeptic
- leave-one-out range -0.43 to -0.22, sign flips 0; without severely affected donors -0.32 (p 0.194, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PCDH17 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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