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 in oligodendrocytes (616 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 42 | 0.91 |
| pathways Reactome | 2 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress SYNJ2 in oligodendrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position 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
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves LRRK2 kinase activity (pT73-Rab10) 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 SYNJ2 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; 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
- SYNJ2 in dopamine neurons, braak-0.20 (p 0.607) → +0.57 (p 0.108)receipt 13207
- SYNJ2 in oligodendrocytes, braak+0.29 (p 0.443) → -0.10 (p 0.790)receipt 13206
Swarm cases
receipt 13207: SYNJ2 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: +0.15 (p 0.549, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.14 (p 0.579, 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 SYNJ2 in dopamine neurons.
case closed: nothing better to follow up.
receipt 13206: SYNJ2 in oligodendrocytes, braak
- power
- full sample +0.10 (p 0.683, n 18), 95% CI -0.38 to +0.54. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.17 (p 0.509, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.11 (p 0.658, n 18). could be the mix.
- skeptic
- leave-one-out range +0.00 to +0.24, sign flips 0; without severely affected donors +0.10 (p 0.683, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SYNJ2 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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