Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.14 (overall 0.08) | 0.14 |
| cell type Human Protein Atlas | cell type enhanced in oligodendrocyte progenitor cells (565 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.27 |
| trials ClinicalTrials.gov | no Parkinson's trials on record: an open field | 1.00 |
| literature PubMed | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 2 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress KIF26B 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 KIF26B 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
- KIF26B in dopamine neurons, braak+0.08 (p 0.838) → -0.28 (p 0.473)receipt 3121
- KIF26B in oligodendrocytes, braak+0.21 (p 0.581) → -0.03 (p 0.944)receipt 3120
Swarm cases
receipt 3121: KIF26B in dopamine neurons, braak
- power
- full sample -0.16 (p 0.515, n 18), 95% CI -0.59 to +0.33. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.15 (p 0.555, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.17 (p 0.509, n 18). could be the mix.
- skeptic
- leave-one-out range -0.30 to -0.06, sign flips 0; without severely affected donors -0.16 (p 0.515, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KIF26B in dopamine neurons.
case closed: nothing better to follow up.
receipt 3120: KIF26B in oligodendrocytes, braak
- power
- full sample -0.04 (p 0.881, n 18), 95% CI -0.50 to +0.44. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.04 (p 0.888, 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 -0.14 to +0.10, sign flips 5; without severely affected donors -0.04 (p 0.881, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KIF26B in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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