Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.76 (overall 0.47) | 0.76 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in pancreatic acinar cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 13 Parkinson's papers of 57 | 0.65 |
| pathways Reactome | in no curated pathway | 0.00 |
Knock down and overexpress TMEM163 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 TMEM163 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
- TMEM163 in dopamine neurons, braak-0.17 (p 0.665) → -0.13 (p 0.732)receipt 0299
- TMEM163 in oligodendrocytes, braak+0.04 (p 0.909) → +0.01 (p 0.982)receipt 0298
Swarm cases
receipt 0299: TMEM163 in dopamine neurons, braak
- power
- full sample -0.05 (p 0.834, n 18), 95% CI -0.51 to +0.42. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.14 (p 0.591, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.44 (p 0.064, n 18). could be the mix.
- skeptic
- leave-one-out range -0.16 to +0.07, sign flips 3; without severely affected donors -0.05 (p 0.834, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TMEM163 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0298: TMEM163 in oligodendrocytes, braak
- power
- full sample +0.06 (p 0.814, n 18), 95% CI -0.42 to +0.51. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.05 (p 0.847, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.04 (p 0.881, n 18). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.20, sign flips 3; without severely affected donors +0.06 (p 0.814, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TMEM163 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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