Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.14 (overall 0.09) | 0.14 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| chemistry Open Targets | hard to drug | 0.24 |
| 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 KIF20B in a dopamine neuron, astrocyte and microglia tri-culture; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- 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 KIF20B in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- KIF20B in dopamine neurons, braak-0.16 (p 0.685) → +0.45 (p 0.227)receipt 2875
Swarm cases
receipt 2875: KIF20B in dopamine neurons, braak
- power
- full sample +0.01 (p 0.983, n 18), 95% CI -0.46 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.01 (p 0.962, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.09 (p 0.735, n 18). could be the mix.
- skeptic
- leave-one-out range -0.14 to +0.15, sign flips 7; without severely affected donors +0.01 (p 0.983, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KIF20B in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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