Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.01 from other evidence | 0.00 |
| cell type Human Protein Atlas | group enriched in microglia (659 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 | 4 pathways; mostly protein handling | 0.90 |
Knock down and overexpress SLCO2B1 in microglia; measure proteasome activity and the load of ubiquitinated protein 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
- proteasome activity and the load of ubiquitinated protein
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves proteasome activity 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 SLCO2B1 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: proteasome activity and the load of ubiquitinated protein; 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
- SLCO2B1 in dopamine neurons, braak-0.35 (p 0.361) → -0.69 (p 0.038)receipt 10010
- SLCO2B1 in microglia, braak-0.56 (p 0.114) → +0.54 (p 0.130)receipt 10009
Swarm cases
receipt 10010: SLCO2B1 in dopamine neurons, braak
- power
- full sample -0.56 (p 0.016, n 18), 95% CI -0.81 to -0.12. the interval excludes zero: something may be there, smaller than a half can see.
- confounder
- adjusted for sex: -0.61 (p 0.0077, n 18). holds up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.65 (p 0.0036, n 18). not the mix.
- skeptic
- leave-one-out range -0.65 to -0.50, sign flips 0; without severely affected donors -0.56 (p 0.016, n 18). robust.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLCO2B1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 10009: SLCO2B1 in microglia, braak
- power
- full sample -0.12 (p 0.640, n 18), 95% CI -0.55 to +0.37. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.09 (p 0.709, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: -0.08 (p 0.761, n 18). could be the mix.
- skeptic
- leave-one-out range -0.26 to -0.01, sign flips 0; without severely affected donors -0.12 (p 0.640, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for SLCO2B1 in microglia.
case closed: nothing better to follow up.
Receipts
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