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 (49 nCPM) | 1.00 |
| chemistry Open Targets | hard to drug | 0.40 |
| 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 mitochondrial quality control | 1.00 |
Knock down and overexpress ERCC5 in microglia; measure PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub) 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
- PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub)
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves PINK1–parkin mitophagy flux (mt-Keima) 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 ERCC5 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: PINK1–parkin mitophagy flux (mt-Keima) and phospho-ubiquitin (pS65-Ub); 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
- ERCC5 in microglia, braak+0.33 (p 0.386) → +0.00 (p 1.000)receipt 11368
- ERCC5 in dopamine neurons, braak+0.45 (p 0.230) → -0.10 (p 0.807)receipt 11369
Swarm cases
receipt 11369: ERCC5 in dopamine neurons, braak
- power
- full sample +0.13 (p 0.603, n 18), 95% CI -0.36 to +0.56. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.13 (p 0.621, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.16 (p 0.526, n 18). could be the mix.
- skeptic
- leave-one-out range +0.04 to +0.28, sign flips 0; without severely affected donors +0.13 (p 0.603, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ERCC5 in dopamine neurons.
case closed: nothing better to follow up.
receipt 11368: ERCC5 in microglia, braak
- power
- full sample +0.01 (p 0.969, n 18), 95% CI -0.46 to +0.47. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.08 (p 0.767, n 18). does not hold up.
- composition
- microglia share of nuclei vs axis -0.11 (p 0.652); controlling for it: +0.18 (p 0.465, n 18). could be the mix.
- skeptic
- leave-one-out range -0.12 to +0.10, sign flips 6; without severely affected donors +0.01 (p 0.969, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ERCC5 in microglia.
case closed: nothing better to follow up.
Receipts
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