Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.71 (overall 0.45) | 0.71 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in t-cells | 0.75 |
| chemistry Open Targets | compounds already reach it: dasatinib anhydrous, enmd-981693, ilorasertib +3 | 1.00 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 61 Parkinson's papers of 3,753 | 0.46 |
| pathways Reactome | 45 pathways; mostly protein handling | 0.90 |
Knock down and overexpress FYN in oligodendrocytes; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves proteasome activity 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 FYN in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- FYN in oligodendrocytes, braak-0.26 (p 0.493) → -0.17 (p 0.668)receipt 0420
- FYN in dopamine neurons, braak-0.59 (p 0.096) → +0.07 (p 0.859)receipt 0421
Swarm cases
receipt 0421: FYN in dopamine neurons, braak
- power
- full sample -0.32 (p 0.194, n 18), 95% CI -0.69 to +0.17. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.34 (p 0.161, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.36 (p 0.148, n 18). could be the mix.
- skeptic
- leave-one-out range -0.44 to -0.23, sign flips 0; without severely affected donors -0.32 (p 0.194, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FYN in dopamine neurons.
case closed: nothing better to follow up.
receipt 0420: FYN in oligodendrocytes, braak
- power
- full sample -0.28 (p 0.258, n 18), 95% CI -0.66 to +0.21. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.21 (p 0.393, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.15 (p 0.561, n 18). could be the mix.
- skeptic
- leave-one-out range -0.48 to -0.22, sign flips 0; without severely affected donors -0.28 (p 0.258, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for FYN in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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