Six readers
| reader | found | score |
|---|---|---|
| genetics Open Targets | genetic association 0.70 (overall 0.60) | 0.70 |
| cell type Human Protein Atlas | expressed broadly, no clear home in brain cells | 0.40 |
| 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 | 60 Parkinson's papers of 308 | 0.46 |
| pathways Reactome | 15 pathways; mostly lysosome and autophagy | 1.00 |
Knock down and overexpress EIF4G1 in a dopamine neuron, astrocyte and microglia tri-culture; measure glucocerebrosidase (GCase) activity and LC3-II and p62 flux and dopamine neuron survival after α-synuclein fibril challenge.
- Cell type
- a dopamine neuron, astrocyte and microglia tri-culture
- Direction
- Both arms: public data does not say which way helps.
- Molecular readout
- glucocerebrosidase (GCase) activity and LC3-II and p62 flux
- Functional readout
- dopamine neuron survival after α-synuclein fibril challenge
- 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 EIF4G1 in a tri-culture of iPSC dopamine neurons, astrocytes and microglia; n = 3 differentiations; readouts: glucocerebrosidase (GCase) activity and LC3-II and p62 flux; dopamine neuron survival after α-synuclein fibril challenge. Controls: non-targeting guide, empty vector. About 8 to 10 weeks, most of it differentiation.
Earlier readings: 2026-10-26 0.66; 2026-10-25 0.66; 2026-10-24 0.66; 2026-10-23 0.66.
Sealed predictions
- EIF4G1 in dopamine neurons, braak+0.31 (p 0.414) → -0.13 (p 0.732)receipt 0558
- EIF4G1 in dopamine neurons, resilience+0.20 (p 0.396) → -0.83 (p 1.000)receipt 0084
- EIF4G1 in dopamine neurons, braak+0.05 (p 0.729) → -0.07 (p 0.662)receipt 0083
Swarm cases
receipt 0558: EIF4G1 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: +0.09 (p 0.728, n 18). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.05 (p 0.854); controlling for it: -0.08 (p 0.748, n 18). could be the mix.
- skeptic
- leave-one-out range -0.15 to +0.14, sign flips 8; 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 EIF4G1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0084: EIF4G1 in dopamine neurons, resilience
- power
- full sample -0.03 (p 0.866, n 55), 95% CI -0.30 to +0.23. the interval is wide: not enough donors to tell.
- confounder
- adjusted for age, sex and PMI: -0.02 (p 0.900, n 55). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis +0.12 (p 0.542); controlling for it: -0.03 (p 0.866, n 55). could be the mix.
- skeptic
- leave-one-out range -0.13 to +0.05, sign flips 4; without severely affected donors -0.05 (p 0.807, n 46). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "differs in resilient donors (Lewy pathology, no parkinsonism)" for EIF4G1 in dopamine neurons.
case closed: nothing better to follow up.
receipt 0083: EIF4G1 in dopamine neurons, braak
- power
- full sample +0.00 (p 0.996, n 84), 95% CI -0.21 to +0.21. the interval sits on zero: probably nothing there.
- confounder
- adjusted for age, sex and PMI: +0.03 (p 0.788, n 84). does not hold up.
- composition
- dopamine neurons share of nuclei vs axis -0.72 (p 1.8e-14); controlling for it: -0.04 (p 0.745, n 84). could be the mix.
- skeptic
- leave-one-out range -0.02 to +0.03, sign flips 45; without severely affected donors +0.02 (p 0.855, n 75). fragile.
- cell type
- no other cell group does better.
- axis
- no measure beats "tracks Braak Lewy-body stage" for EIF4G1 in dopamine neurons.
case closed: nothing better to follow up.
Receipts
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