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 in astrocytes (638 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 | 1 Parkinson's papers of 104 | 0.91 |
| pathways Reactome | 22 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress CAMK2G 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 CAMK2G 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
- CAMK2G in dopamine neurons, braak-0.45 (p 0.230) → -0.68 (p 0.043)receipt 6619
- CAMK2G in astrocytes, braak+0.13 (p 0.739) → +0.11 (p 0.784)receipt 6618
Swarm cases
receipt 6619: CAMK2G in dopamine neurons, braak
- power
- full sample -0.46 (p 0.055, n 18), 95% CI -0.76 to +0.01. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.49 (p 0.041, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.53 (p 0.023, n 18). not the mix.
- skeptic
- leave-one-out range -0.54 to -0.39, sign flips 0; without severely affected donors -0.46 (p 0.055, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CAMK2G in dopamine neurons.
case closed: nothing better to follow up.
receipt 6618: CAMK2G in astrocytes, braak
- power
- full sample +0.13 (p 0.609, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.21 (p 0.408, n 18). does not hold up.
- composition
- astrocytes share of nuclei vs axis -0.21 (p 0.413); controlling for it: +0.24 (p 0.328, n 18). could be the mix.
- skeptic
- leave-one-out range +0.00 to +0.24, sign flips 0; without severely affected donors +0.13 (p 0.609, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for CAMK2G in astrocytes.
case closed: nothing better to follow up.
Receipts
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