Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.08 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in renal collecting duct principal cells | 0.75 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | 2 Parkinson's papers of 328 | 0.85 |
| pathways Reactome | 3 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress ANK3 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 ANK3 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
- ANK3 in oligodendrocytes, braak-0.54 (p 0.136) → +0.10 (p 0.802)receipt 3382
- ANK3 in dopamine neurons, braak+0.11 (p 0.785) → +0.04 (p 0.927)receipt 3383
Swarm cases
receipt 3383: ANK3 in dopamine neurons, braak
- power
- full sample +0.06 (p 0.820, n 18), 95% CI -0.42 to +0.51. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.935, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.11 (p 0.652, n 18). could be the mix.
- skeptic
- leave-one-out range -0.06 to +0.19, sign flips 5; without severely affected donors +0.06 (p 0.820, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ANK3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 3382: ANK3 in oligodendrocytes, braak
- power
- full sample -0.13 (p 0.603, n 18), 95% CI -0.56 to +0.36. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.14 (p 0.567, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: -0.13 (p 0.609, n 18). could be the mix.
- skeptic
- leave-one-out range -0.28 to -0.03, sign flips 0; without severely affected donors -0.13 (p 0.603, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ANK3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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