Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (1616 nCPM) | 1.00 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 93 | 0.91 |
| pathways Reactome | 1 pathway; mostly immune signalling | 0.90 |
Knock down and overexpress TRIM2 in oligodendrocytes; measure IL-1β and TNF release and surface HLA-DR 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
- IL-1β and TNF release and surface HLA-DR
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves IL-1β 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 TRIM2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: IL-1β and TNF release and surface HLA-DR; 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
- TRIM2 in dopamine neurons, braak+0.30 (p 0.430) → -0.02 (p 0.963)receipt 3181
- TRIM2 in oligodendrocytes, braak+0.15 (p 0.697) → -0.08 (p 0.842)receipt 3180
Swarm cases
receipt 3181: TRIM2 in dopamine neurons, braak
- power
- full sample +0.12 (p 0.627, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.10 (p 0.690, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.29 (p 0.243, n 18). could be the mix.
- skeptic
- leave-one-out range +0.02 to +0.26, sign flips 0; without severely affected donors +0.12 (p 0.627, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TRIM2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3180: TRIM2 in oligodendrocytes, braak
- power
- full sample +0.07 (p 0.787, n 18), 95% CI -0.41 to +0.52. 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
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.23 (p 0.365, n 18). could be the mix.
- skeptic
- leave-one-out range -0.05 to +0.17, sign flips 3; without severely affected donors +0.07 (p 0.787, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TRIM2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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