Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.07 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocytes (612 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 | 7 Parkinson's papers of 394 | 0.73 |
| pathways Reactome | 1 pathway; mostly vesicle traffic | 1.00 |
Knock down and overexpress SORT1 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 SORT1 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
- SORT1 in dopamine neurons, braak-0.40 (p 0.285) → +0.76 (p 0.017)receipt 3692
- SORT1 in oligodendrocytes, braak-0.24 (p 0.529) → -0.05 (p 0.891)receipt 3691
Swarm cases
receipt 3692: SORT1 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: +0.16 (p 0.521, 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 0.111, n 18). could be the mix.
- skeptic
- leave-one-out range +0.07 to +0.30, 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 SORT1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3691: SORT1 in oligodendrocytes, braak
- power
- full sample -0.07 (p 0.794, n 18), 95% CI -0.52 to +0.41. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.11 (p 0.664, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.07 (p 0.781, n 18). could be the mix.
- skeptic
- leave-one-out range -0.20 to +0.04, sign flips 3; without severely affected donors -0.07 (p 0.794, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SORT1 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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