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 oligodendrocyte progenitor cells; strongest in neutrophils | 0.75 |
| chemistry Open Targets | compounds already reach it: astegolimab, imsidolimab, spesolimab | 0.90 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 1 Parkinson's papers of 262 | 0.91 |
| pathways Reactome | 6 pathways; mostly immune signalling | 0.90 |
Knock down and overexpress IL1RAP 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; existing compounds already reach the inhibition arm.
- 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 IL1RAP 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
- IL1RAP in oligodendrocytes, braak-0.29 (p 0.443) → +0.07 (p 0.859)receipt 15498
- IL1RAP in dopamine neurons, braak+0.83 (p 0.005) → +0.12 (p 0.749)receipt 15499
Swarm cases
receipt 15499: IL1RAP in dopamine neurons, braak
- power
- full sample +0.35 (p 0.150, n 18), 95% CI -0.14 to +0.70. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.35 (p 0.150, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.39 (p 0.107, n 18). could be the mix.
- skeptic
- leave-one-out range +0.27 to +0.56, sign flips 0; without severely affected donors +0.35 (p 0.150, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IL1RAP in dopamine neurons.
case closed: nothing better to follow up.
receipt 15498: IL1RAP in oligodendrocytes, braak
- power
- full sample -0.19 (p 0.439, n 18), 95% CI -0.61 to +0.30. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.20 (p 0.434, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.19 (p 0.455, n 18). could be the mix.
- skeptic
- leave-one-out range -0.37 to -0.09, sign flips 0; without severely affected donors -0.19 (p 0.439, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for IL1RAP in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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