Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.00 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in neutrophils | 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 | no papers tie it to Parkinson's yet | 1.00 |
| pathways Reactome | 8 pathways; mostly vesicle traffic | 1.00 |
Knock down and overexpress SH3KBP1 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 SH3KBP1 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
- SH3KBP1 in microglia, braak-0.14 (p 0.724) → -0.72 (p 0.028)receipt 12368
- SH3KBP1 in dopamine neurons, braak+0.20 (p 0.597) → -0.19 (p 0.631)receipt 12369
Swarm cases
receipt 12369: SH3KBP1 in dopamine neurons, braak
- power
- full sample +0.02 (p 0.942, n 18), 95% CI -0.45 to +0.48. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.04 (p 0.867, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.06 (p 0.820, n 18). could be the mix.
- skeptic
- leave-one-out range -0.10 to +0.16, sign flips 7; without severely affected donors +0.02 (p 0.942, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3KBP1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 12368: SH3KBP1 in microglia, braak
- power
- full sample -0.24 (p 0.341, n 18), 95% CI -0.63 to +0.26. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.21 (p 0.398, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.19 (p 0.444, n 18). could be the mix.
- skeptic
- leave-one-out range -0.38 to -0.15, sign flips 0; without severely affected donors -0.24 (p 0.341, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SH3KBP1 in microglia.
case closed: nothing better to follow up.
Receipts
loading the receipts