Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced in microglia (82 nCPM) | 1.00 |
| chemistry Open Targets | reachable by antibody | 0.45 |
| 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 | 3 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress RAB39A in microglia; measure LRRK2 kinase activity (pT73-Rab10) and lysosome position and uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release).
- Cell type
- microglia
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- LRRK2 kinase activity (pT73-Rab10) and lysosome position
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- 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 RAB39A in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: LRRK2 kinase activity (pT73-Rab10) and lysosome position; uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release). Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- RAB39A in microglia, braak+0.17 (p 0.663) → -0.18 (p 0.639)receipt 12155
- RAB39A in dopamine neurons, braak+0.24 (p 0.529) → +0.06 (p 0.888)receipt 12156
Swarm cases
receipt 12156: RAB39A in dopamine neurons, braak
- power
- full sample +0.28 (p 0.258, n 18), 95% CI -0.21 to +0.66. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.25 (p 0.315, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.23 (p 0.369, n 18). could be the mix.
- skeptic
- leave-one-out range +0.16 to +0.42, sign flips 0; without severely affected donors +0.28 (p 0.258, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for RAB39A in dopamine neurons.
case closed: nothing better to follow up.
receipt 12155: RAB39A in microglia, braak
- power
- full sample -0.06 (p 0.820, n 18), 95% CI -0.51 to +0.42. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.03 (p 0.922, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.03 (p 0.922, n 18). could be the mix.
- skeptic
- leave-one-out range -0.21 to +0.05, 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 RAB39A in microglia.
case closed: nothing better to follow up.
Receipts
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