Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in early spermatids | 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 | 1 Parkinson's papers of 87 | 0.91 |
| pathways Reactome | 8 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress EXOSC3 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 EXOSC3 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
- EXOSC3 in dopamine neurons, braak-0.04 (p 0.911) → +0.42 (p 0.258)receipt 16501
- EXOSC3 in oligodendrocytes, braak-0.11 (p 0.777) → -0.05 (p 0.894)receipt 16500
Swarm cases
receipt 16501: EXOSC3 in dopamine neurons, braak
- power
- full sample +0.18 (p 0.482, n 18), 95% CI -0.32 to +0.59. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.24 (p 0.328, 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 +0.08 to +0.33, sign flips 0; without severely affected donors +0.18 (p 0.482, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for EXOSC3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 16500: EXOSC3 in oligodendrocytes, braak
- power
- full sample -0.10 (p 0.696, n 18), 95% CI -0.54 to +0.39. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.05 (p 0.840, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.11 (p 0.677, n 18). could be the mix.
- skeptic
- leave-one-out range -0.25 to +0.03, sign flips 1; without severely affected donors -0.10 (p 0.696, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for EXOSC3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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