Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.42 (overall 0.27) | 0.42 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (7073 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.36 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 501 | 0.85 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress LRP1B 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 LRP1B 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
- LRP1B in dopamine neurons, braak+0.90 (p 0.001) → -0.38 (p 0.316)receipt 1511
- LRP1B in oligodendrocytes, braak+0.20 (p 0.597) → +0.17 (p 0.665)receipt 1510
Swarm cases
receipt 1511: LRP1B in dopamine neurons, braak
- power
- full sample +0.31 (p 0.211, n 18), 95% CI -0.18 to +0.68. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.27 (p 0.281, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.24 (p 0.328, n 18). could be the mix.
- skeptic
- leave-one-out range +0.24 to +0.50, sign flips 0; without severely affected donors +0.31 (p 0.211, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LRP1B in dopamine neurons.
case closed: nothing better to follow up.
receipt 1510: LRP1B in oligodendrocytes, braak
- power
- full sample +0.19 (p 0.460, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.434, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.18 (p 0.487, n 18). could be the mix.
- skeptic
- leave-one-out range +0.08 to +0.37, sign flips 0; without severely affected donors +0.19 (p 0.460, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for LRP1B in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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