Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.55 (overall 0.34) | 0.55 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (322 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 | 1 Parkinson's papers of 16 | 0.91 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress PLPP4 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 PLPP4 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
- PLPP4 in dopamine neurons, braak-0.21 (p 0.581) → +0.10 (p 0.790)receipt 0960
- PLPP4 in oligodendrocytes, braak+0.30 (p 0.436) → +0.12 (p 0.753)receipt 0959
Swarm cases
receipt 0960: PLPP4 in dopamine neurons, braak
- power
- full sample -0.03 (p 0.901, n 18), 95% CI -0.49 to +0.44. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.03 (p 0.901, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.00 (p 0.990, n 18). could be the mix.
- skeptic
- leave-one-out range -0.15 to +0.09, sign flips 7; without severely affected donors -0.03 (p 0.901, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PLPP4 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0959: PLPP4 in oligodendrocytes, braak
- power
- full sample +0.24 (p 0.328, n 18), 95% CI -0.25 to +0.64. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.26 (p 0.306, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.26 (p 0.306, n 18). could be the mix.
- skeptic
- leave-one-out range +0.15 to +0.32, sign flips 0; without severely affected donors +0.24 (p 0.328, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for PLPP4 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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