Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.03 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including astrocytes; strongest in ependymal 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 | 3 Parkinson's papers of 151 | 0.82 |
| pathways Reactome | 2 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress KIAA0319 in astrocytes; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position and α-synuclein uptake and degradation, and dopamine neuron survival in co-culture.
- Cell type
- astrocytes
- 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 degradation, and dopamine neuron survival in co-culture
- 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 KIAA0319 in iPSC-derived midbrain astrocytes; n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; α-synuclein uptake and degradation, and dopamine neuron survival in co-culture. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- KIAA0319 in dopamine neurons, braak+0.17 (p 0.666) → +0.04 (p 0.911)receipt 6839
- KIAA0319 in astrocytes, braak-0.19 (p 0.631) → -0.12 (p 0.753)receipt 6838
Swarm cases
receipt 6839: KIAA0319 in dopamine neurons, braak
- power
- full sample +0.16 (p 0.538, n 18), 95% CI -0.34 to +0.58. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.418, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.16 (p 0.532, n 18). could be the mix.
- skeptic
- leave-one-out range +0.06 to +0.30, sign flips 0; without severely affected donors +0.16 (p 0.538, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KIAA0319 in dopamine neurons.
case closed: nothing better to follow up.
receipt 6838: KIAA0319 in astrocytes, braak
- power
- full sample -0.19 (p 0.450, n 18), 95% CI -0.60 to +0.30. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.19 (p 0.450, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: -0.08 (p 0.767, n 18). could be the mix.
- skeptic
- leave-one-out range -0.37 to -0.11, sign flips 0; without severely affected donors -0.19 (p 0.450, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for KIAA0319 in astrocytes.
case closed: nothing better to follow up.
Receipts
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