Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.28 (overall 0.18) | 0.28 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (4301 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 | 12 Parkinson's papers of 1,070 | 0.66 |
| pathways Reactome | 1 pathway; mostly other | 0.30 |
Knock down and overexpress TNR 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 TNR 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
- TNR in dopamine neurons, braak+0.04 (p 0.919) → -0.20 (p 0.599)receipt 2111
- TNR in oligodendrocytes, braak-0.76 (p 0.019) → +0.32 (p 0.407)receipt 2110
Swarm cases
receipt 2111: TNR in dopamine neurons, braak
- power
- full sample -0.18 (p 0.465, n 18), 95% CI -0.60 to +0.31. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.14 (p 0.567, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.46 (p 0.057, n 18). could be the mix.
- skeptic
- leave-one-out range -0.27 to -0.07, sign flips 0; without severely affected donors -0.18 (p 0.465, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNR in dopamine neurons.
case closed: nothing better to follow up.
receipt 2110: TNR in oligodendrocytes, braak
- power
- full sample -0.25 (p 0.315, n 18), 95% CI -0.64 to +0.24. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.25 (p 0.315, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.31 (p 0.204, n 18). could be the mix.
- skeptic
- leave-one-out range -0.39 to -0.16, sign flips 0; without severely affected donors -0.25 (p 0.315, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TNR in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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