Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.02 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocyte progenitor cells; strongest in podocytes | 0.75 |
| 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 | 3 Parkinson's papers of 1,276 | 0.82 |
| pathways Reactome | 2 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress TAP1 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 TAP1 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
- TAP1 in dopamine neurons, braak-0.51 (p 0.161) → +0.05 (p 0.893)receipt 8396
- TAP1 in oligodendrocytes, braak-0.44 (p 0.233) → +0.29 (p 0.456)receipt 8395
Swarm cases
receipt 8396: TAP1 in dopamine neurons, braak
- power
- full sample -0.17 (p 0.504, n 18), 95% CI -0.59 to +0.32. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.13 (p 0.609, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.11 (p 0.658, n 18). could be the mix.
- skeptic
- leave-one-out range -0.34 to -0.07, sign flips 0; without severely affected donors -0.17 (p 0.504, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TAP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 8395: TAP1 in oligodendrocytes, braak
- power
- full sample -0.20 (p 0.418, n 18), 95% CI -0.61 to +0.29. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.26 (p 0.298, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.16 (p 0.515, n 18). could be the mix.
- skeptic
- leave-one-out range -0.35 to -0.11, sign flips 0; without severely affected donors -0.20 (p 0.418, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for TAP1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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