Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | no genetic evidence; overall 0.05 from other evidence | 0.00 |
| cell type Human Protein Atlas | cell type enhanced, including oligodendrocytes; strongest in mast cells | 0.75 |
| chemistry Open Targets | a small-molecule pocket | 0.60 |
| 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 lysosome and autophagy | 1.00 |
Knock down and overexpress ACER3 in oligodendrocytes; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and α-synuclein uptake and myelin basic protein output under oxidative stress.
- Cell type
- oligodendrocytes
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- α-synuclein uptake and myelin basic protein output under oxidative stress
- Rule-out
- If neither arm moves glucocerebrosidase (GCase) 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 ACER3 in iPSC-derived oligodendrocytes; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; α-synuclein uptake and myelin basic protein output under oxidative stress. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Sealed predictions
- ACER3 in dopamine neurons, braak+0.05 (p 0.891) → +0.78 (p 0.013)receipt 5188
- ACER3 in oligodendrocytes, braak+0.53 (p 0.138) → +0.34 (p 0.375)receipt 5187
Swarm cases
receipt 5188: ACER3 in dopamine neurons, braak
- power
- full sample +0.18 (p 0.476, n 18), 95% CI -0.31 to +0.60. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.20 (p 0.424, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: +0.27 (p 0.273, n 18). could be the mix.
- skeptic
- leave-one-out range +0.08 to +0.29, sign flips 0; without severely affected donors +0.18 (p 0.476, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ACER3 in dopamine neurons.
case closed: nothing better to follow up.
receipt 5187: ACER3 in oligodendrocytes, braak
- power
- full sample +0.39 (p 0.109, n 18), 95% CI -0.09 to +0.73. the interval is wide: not enough donors to tell.
- confounder
- adjusted for sex: +0.37 (p 0.127, n 18). does not hold up.
- composition
- oligodendrocytes share of nuclei vs axis +0.03 (p 0.915); controlling for it: +0.48 (p 0.043, n 18). not the mix.
- skeptic
- leave-one-out range +0.31 to +0.49, sign flips 0; without severely affected donors +0.39 (p 0.109, n 18). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for ACER3 in oligodendrocytes.
case closed: nothing better to follow up.
Receipts
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