Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.34 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including microglia; strongest in enterocytes | 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 | 1 pathway; mostly iron and oxidative stress | 0.80 |
Knock down and overexpress ACY3 in microglia; measure reactive oxygen species (CellROX) and lipid peroxidation and labile iron 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
- reactive oxygen species (CellROX) and lipid peroxidation and labile iron
- Functional readout
- uptake and clearance of α-synuclein fibrils and NLRP3 inflammasome activation (IL-1β release)
- Rule-out
- If neither arm moves reactive oxygen species (CellROX) 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 ACY3 in iPSC-derived microglia (iMGL); n = 3 differentiations; readouts: reactive oxygen species (CellROX) and lipid peroxidation and labile iron; 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
- ACY3 in microglia, braak-0.29 (p 0.457) → +0.08 (p 0.842)receipt 0952
- ACY3 in dopamine neurons, braak+0.27 (p 0.487) → -0.57 (p 0.110)receipt 0953
Swarm cases
receipt 0953: ACY3 in dopamine neurons, braak
- power
- full sample -0.24 (p 0.332, n 18), 95% CI -0.64 to +0.25. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: -0.29 (p 0.243, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.25 (p 0.319, n 18). could be the mix.
- skeptic
- leave-one-out range -0.43 to -0.16, sign flips 0; without severely affected donors -0.24 (p 0.332, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ACY3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0952: ACY3 in microglia, braak
- power
- full sample -0.08 (p 0.754, n 18), 95% CI -0.53 to +0.40. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.02 (p 0.942, 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 -0.24 to +0.05, sign flips 4; 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 ACY3 in microglia.
case closed: nothing better to follow up.
Receipts
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