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 in microglia (85 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.00 |
| 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 | 2 pathways; mostly protein handling | 0.90 |
Knock down and overexpress UBE2F 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 UBE2F 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
- UBE2F in dopamine neurons, braak-0.20 (p 0.597) → +0.26 (p 0.499)receipt 14232
- UBE2F in microglia, braak-0.36 (p 0.336) → +0.54 (p 0.130)receipt 14231
Swarm cases
receipt 14232: UBE2F in dopamine neurons, braak
- power
- full sample -0.00 (p 0.997, n 18), 95% CI -0.47 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.01 (p 0.976, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.02 (p 0.935, n 18). could be the mix.
- skeptic
- leave-one-out range -0.13 to +0.10, sign flips 9; without severely affected donors -0.00 (p 0.997, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for UBE2F in dopamine neurons.
case closed: nothing better to follow up.
receipt 14231: UBE2F in microglia, braak
- power
- full sample +0.08 (p 0.754, n 18), 95% CI -0.40 to +0.53. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.07 (p 0.781, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.25 (p 0.315, n 18). could be the mix.
- skeptic
- leave-one-out range -0.03 to +0.19, sign flips 3; without severely affected donors +0.08 (p 0.754, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for UBE2F in microglia.
case closed: nothing better to follow up.
Receipts
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