Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.38 (overall 0.23) | 0.38 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (1525 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 | 1 pathway; mostly other | 0.30 |
Knock down and overexpress PTPRK 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 PTPRK 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
- PTPRK in dopamine neurons, braak+0.26 (p 0.498) → +0.21 (p 0.586)receipt 1844
- PTPRK in oligodendrocytes, braak+0.69 (p 0.039) → +0.38 (p 0.311)receipt 1843
Swarm cases
receipt 1844: PTPRK in dopamine neurons, braak
- power
- full sample +0.18 (p 0.476, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.17 (p 0.504, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.19 (p 0.460, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.33, sign flips 0; without severely affected donors +0.18 (p 0.476, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PTPRK in dopamine neurons.
case closed: nothing better to follow up.
receipt 1843: PTPRK in oligodendrocytes, braak
- power
- full sample +0.53 (p 0.022, n 18), 95% CI +0.09 to +0.80. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: +0.53 (p 0.022, n 18). holds up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.70 (p 0.0012, n 18). not the mix.
- skeptic
- leave-one-out range +0.47 to +0.67, sign flips 0; without severely affected donors +0.53 (p 0.022, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PTPRK in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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